Showing papers by "University of Colorado Denver published in 2001"
European Bioinformatics Institute1, TigerLogic2, Stanford University3, University of California, Berkeley4, University of Pennsylvania5, Harvard University6, Imperial College London7, Rockefeller University8, Katholieke Universiteit Leuven9, Utrecht University10, University of Colorado Denver11, Max Planck Society12
TL;DR: The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools.
Abstract: Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.
4,030 citations
TL;DR: The findings suggest that the currently used equation for predicting maximal heart rate in older adults underestimates HRmax, which would have the effect of underestimating the true level of physical stress imposed during exercise testing and the appropriate intensity of prescribed exercise programs.
2,924 citations
TL;DR: The results demonstrate that underdiagnosis of PAD in primary care practice may be a barrier to effective secondary prevention of the high ischemic cardiovascular risk associated with PAD.
Abstract: ContextPeripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis
that is common and is associated with an increased risk of death and ischemic
events, yet may be underdiagnosed in primary care practice.ObjectiveTo assess the feasibility of detecting PAD in primary care clinics,
patient and physician awareness of PAD, and intensity of risk factor treatment
and use of antiplatelet therapies in primary care clinics.Design and SettingThe PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS)
program, a multicenter, cross-sectional study conducted at 27 sites in 25
cities and 350 primary care practices throughout the United States in June-October
1999.PatientsA total of 6979 patients aged 70 years or older or aged 50 through 69
years with history of cigarette smoking or diabetes were evaluated by history
and by measurement of the ankle-brachial index (ABI). PAD was considered present
if the ABI was 0.90 or less, if it was documented in the medical record, or
if there was a history of limb revascularization. Cardiovascular disease (CVD)
was defined as a history of atherosclerotic coronary, cerebral, or abdominal
aortic aneurysmal disease.Main Outcome MeasuresFrequency of detection of PAD; physician and patient awareness of PAD
diagnosis; treatment intensity in PAD patients compared with treatment of
other forms of CVD and with patients without clinical evidence of atherosclerosis.ResultsPAD was detected in 1865 patients (29%); 825 of these (44%) had PAD
only, without evidence of CVD. Overall, 13% had PAD only, 16% had PAD and
CVD, 24% had CVD only, and 47% had neither PAD nor CVD (the reference group).
There were 457 patients (55%) with newly diagnosed PAD only and 366 (35%)
with PAD and CVD who were newly diagnosed during the survey. Eighty-three
percent of patients with prior PAD were aware of their diagnosis, but only
49% of physicians were aware of this diagnosis. Among patients with PAD, classic
claudication was distinctly uncommon (11%). Patients with PAD had similar
atherosclerosis risk factor profiles compared with those who had CVD. Smoking
behavior was more frequently treated in patients with new (53%) and prior
PAD (51%) only than in those with CVD only (35%; P
<.001). Hypertension was treated less frequently in new (84%) and prior
PAD (88%) only vs CVD only (95%; P <.001) and
hyperlipidemia was treated less frequently in new (44%) and prior PAD (56%)
only vs CVD only (73%, P<.001). Antiplatelet medications
were prescribed less often in patients with new (33%) and prior PAD (54%)
only vs CVD only (71%, P<.001). Treatment intensity
for diabetes and use of hormone replacement therapy in women were similar
across all groups.ConclusionsPrevalence of PAD in primary care practices is high, yet physician awareness
of the PAD diagnosis is relatively low. A simple ABI measurement identified
a large number of patients with previously unrecognized PAD. Atherosclerosis
risk factors were very prevalent in PAD patients, but these patients received
less intensive treatment for lipid disorders and hypertension and were prescribed
antiplatelet therapy less frequently than were patients with CVD. These results
demonstrate that underdiagnosis of PAD in primary care practice may be a barrier
to effective secondary prevention of the high ischemic cardiovascular risk
associated with PAD.
2,446 citations
TL;DR: After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa.
Abstract: Background Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. Methods We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or undergo sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who underwent sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of –3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. Results The mean (±SD)...
2,114 citations
TL;DR: In this article, the ADAMTS family of zinc metalloproteinase genes (ADAMTS13) was identified as the molecular mechanism responsible for TTP, and it was shown that the deficiency of ADADTS13 is the molecular mechanisms responsible for the development of TTP.
Abstract: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von Willebrand factor (VWF) observed in normal plasma is decreased in TTP patients. However, the identity of the responsible protease and its role in the pathophysiology of TTP remain unknown. We performed genome-wide linkage analysis in four pedigrees of humans with congenital TTP and mapped the responsible genetic locus to chromosome 9q34. A predicted gene in the identified interval corresponds to a segment of a much larger transcript, identifying a new member of the ADAMTS family of zinc metalloproteinase genes (ADAMTS13). Analysis of patients' genomic DNA identified 12 mutations in the ADAMTS13 gene, accounting for 14 of the 15 disease alleles studied. We show that deficiency of ADAMTS13 is the molecular mechanism responsible for TTP, and suggest that physiologic proteolysis of VWF and/or other ADAMTS13 substrates is required for normal vascular homeostasis.
1,629 citations
TL;DR: Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal-cell cancer than does interferons therapy alone.
Abstract: Background The value of nephrectomy in metastatic renal-cell cancer has long been debated. Several nonrandomized studies suggest a higher rate of response to systemic therapy and longer survival in patients who have undergone nephrectomy. Methods We randomly assigned patients with metastatic renal-cell cancer who were acceptable candidates for nephrectomy to undergo radical nephrectomy followed by therapy with interferon alfa-2b or to receive interferon alfa-2b therapy alone. The primary end point was survival, and the secondary end point was a response of the tumor to treatment. Results The median survival of 120 eligible patients assigned to surgery followed by interferon was 11.1 months, and among the 121 eligible patients assigned to interferon alone it was 8.1 months (P=0.05). The difference in median survival between the two groups was independent of performance status, metastatic site, and the presence or absence of a measurable metastatic lesion. Conclusions Nephrectomy followed by interferon ther...
1,547 citations
TL;DR: PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer, and overall costs on the PC arm were higher than on the VC arm because of drug costs.
Abstract: PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non–small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m2 over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P = .002...
1,139 citations
TL;DR: Patients with peripheral arterial disease, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as do patients with ahistory of coronary or cerebrovascular disease.
Abstract: Peripheral arterial disease, which is caused by atherosclerotic occlusion of the arteries to the legs, is an important manifestation of systemic atherosclerosis. The age-adjusted prevalence of peripheral arterial disease is approximately 12 percent, and the disorder affects men and women equally (Table 1).7,8 Patients with peripheral arterial disease, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as do patients with a history of coronary or cerebrovascular disease (Table 2).12,15 In patients with peripheral arterial disease, the rate of death from all causes . . .
1,087 citations
TL;DR: The authors review the “cancer‐related check‐up,” clinical encounters that provide case‐finding and health counseling opportunities, and the ACS is issuing an updated narrative related to testing for early lung cancer detection for clinicians and individuals at high risk of lung cancer in light of emerging data on new imaging technologies.
Abstract: Updates to the American Cancer Society (ACS) guidelines regarding screening for the early detection of prostate, colorectal, and endometrial cancers, based on the recommendations of recent ACS workshops, are presented. Additionally, the authors review the "cancer-related check-up," clinical encounters that provide case-finding and health counseling opportunities. Finally, the ACS is issuing an updated narrative related to testing for early lung cancer detection for clinicians and individuals at high risk of lung cancer in light of emerging data on new imaging technologies. Although it is likely that current screening protocols will be supplanted in the future by newer, more effective technologies, the establishment of an organized and systematic approach to early cancer detection would lead to greater utilization of existing technology and greater progress in cancer control.
824 citations
TL;DR: In this article, the authors reported five elderly men with the fragile X premutation who had a progressive action tremor associated with executive function deficits and generalized brain atrophy, and they had elevated fragile X mental retardation 1 gene (FMR1) messenger RNA and normal or borderline levels of FMR1 protein.
Abstract: The authors report five elderly men with the fragile X premutation who had a progressive action tremor associated with executive function deficits and generalized brain atrophy. These individuals had elevated fragile X mental retardation 1 gene (FMR1) messenger RNA and normal or borderline levels of FMR1 protein. The authors propose that elevations of FMR1 messenger RNA may be causative for a neurodegenerative syndrome in a subgroup of elderly men with the FMR1 premutation.
817 citations
TL;DR: Numerical results establish that the LOBPCG method is practically as efficient as the ``ideal'' algorithm when the same preconditioner is used in both methods, and direct numerical comparisons with the Jacobi--Davidson method show that the method is more robust and converges almost two times faster.
Abstract: We describe new algorithms of the locally optimal block preconditioned conjugate gradient (LOBPCG) method for symmetric eigenvalue problems, based on a local optimization of a three-term recurrence, and suggest several other new methods. To be able to compare numerically different methods in the class, with different preconditioners, we propose a common system of model tests, using random preconditioners and initial guesses. As the "ideal" control algorithm, we advocate the standard preconditioned conjugate gradient method for finding an eigenvector as an element of the null-space of the corresponding homogeneous system of linear equations under the assumption that the eigenvalue is known. We recommend that every new preconditioned eigensolver be compared with this "ideal" algorithm on our model test problems in terms of the speed of convergence, costs of every iteration, and memory requirements. We provide such comparison for our LOBPCG method. Numerical results establish that our algorithm is practically as efficient as the ``ideal'' algorithm when the same preconditioner is used in both methods. We also show numerically that the LOBPCG method provides approximations to first eigenpairs of about the same quality as those by the much more expensive global optimization method on the same generalized block Krylov subspace. We propose a new version of block Davidson's method as a generalization of the LOBPCG method. Finally, direct numerical comparisons with the Jacobi--Davidson method show that our method is more robust and converges almost two times faster.
TL;DR: Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema.
Abstract: Background Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. Methods In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression, we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. Results A comparison of the children i...
TL;DR: It is shown that rapid progestin-induced activation of Src and downstream MAP kinase in mammalian cells is dependent on PR-SH3 domain interaction, but not on the transcriptional activity of PR.
TL;DR: In this article, the authors investigated the degree to which selected behavioral (information that customers used when making the online service decision, their service usage), attitudinal (risk-taking propensity), and demographic (income and education) factors are effective in discriminating between continuers and switchers.
Abstract: With a quarter of a billion Internet users worldwide and estimates of more than one-half billion people online by the year 2003, growth in the online services industry has been exponential. With this growth has come concern about customer “churn”, a concern that parallels issues of customer switching behavior in services industries in general. This manuscript reports results of two field studies, conducted among two randomly selected samples of online service users, that investigate the degree to which selected behavioral (information that customers used when making the online service decision, their service usage), attitudinal (risk-taking propensity), and demographic (income and education) factors are effective in discriminating between continuers and switchers. The research in Study 1 is replicated in Study 2 and extended to consider additional attitudinal factors of satisfaction and involvement. Implications for managers and researchers are discussed.
TL;DR: The finding of two FXS subgroups raises a hypothesis of additional genetic influences in the FXS autism group, warranting further genetic studies.
Abstract: This study was designed to explore the behavioral phenotype of autism in a group of young children with fragile X syndrome (FXS). Twenty-four children with FXS, ages 21 to 48 months, were compared with two well-matched groups: 27 children with autism (AD) and 23 children with other developmental delays (DD), on two standardized autism instruments, as well as on measures of development and adaptive behavior. Two FXS subgroups emerged. One subgroup (n = 16) did not meet study criteria for autism. Their profiles on the autism instruments and the developmental instruments were virtually identical to the other DD group. The other FXS subgroup (n = 8, or 33% of the total FXS group) met study criteria for autism. Their profiles on the autism instruments were virtually identical to the group with autism. The finding of two FXS subgroups raises a hypothesis of additional genetic influences in the FXS autism group, warranting further genetic studies.
TL;DR: Positive excess return for smaller firms shows that smaller firms can leverage the lower price/performance ratio of new IT and reap greater rewards from IT investments than larger firms.
Abstract: Evaluating the effectiveness of Information Technology (IT) investments has always been an elusive but important goal of IS researchers. This study builds on a prior study that examined changes in the market value of the firm as reflected by the stock price in response to IT investment announcements. Data on stock prices were analyzed for 238 publicly traded companies. In addition to the stock price analysis, reaction of trading volume to the announcements was also examined to identify whether IT investment announcements affect investors' beliefs about IT value. Potentially confounding factors such as industry, size, and time lag effects were also analyzed. Size and time lag effects were found for all IT investment announcements. Reactions of price and volume were negatively related to firm size and became more positive over time. The positive excess return for smaller firms shows that smaller firms can leverage the lower price/performance ratio of new IT and reap greater rewards from IT investments than larger firms. Also, the result of time lag effect demonstrates that the stock market has recently begun to identify both tangible and intangible benefits of IT investments. For recent IT investment announcements, industry classification and firm size also affected the reactions of stock price to the announcements. This study provides optimism on the stock market reaction to IT investment announcements as well as further insight into the study of IT impacts on organizational performance.
TL;DR: In this paper, a special issue devoted to the subject of management accounting change is presented, which comprises five studies that address various dimensions of this important research area, each study adopting different perspectives and different research methodologies.
TL;DR: In this paper, the proinflammatory caspase-1, which cleaves precursors of IL-1 beta and IL-18, was found to protect mice from acute renal failure.
Abstract: We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1 beta and IL-18, were protected against ischemic acute renal failure (ARF). Caspase-1(-/-) mice developed less ischemic ARF as judged by renal function and renal histology. These animals had significantly reduced blood urea nitrogen and serum creatinine levels and a lower morphological tubular necrosis score than did wild-type mice with ischemic ARF. Since caspase-1 activates IL-18, lack of mature IL-18 might protect these caspase-1(-/-) mice from ARF. In wild-type animals, we found that ARF causes kidney IL-18 levels to more than double and induces the conversion of the IL-18 precursor to the mature form. This conversion is not observed in caspase-1(-/-) ARF mice or sham-operated controls. We then injected wild-type mice with IL-18-neutralizing antiserum before the ischemic insult and found a similar degree of protection from ARF as seen in caspase-1(-/-) mice. In addition, we observed a fivefold increase in myeloperoxidase activity in control mice with ARF, but no such increase in caspase-1(-/-) or IL-18 antiserum-treated mice. Finally, we confirmed histologically that caspase-1(-/-) mice show decreased neutrophil infiltration, indicating that the deleterious role of IL-18 in ischemic ARF may be due to increased neutrophil infiltration.
TL;DR: While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.
Abstract: Objective To identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients. Design Evaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics. Setting Eight clinics specializing in the care of HIV-1 infected patients. Patients A total of 1077 patients were evaluated for signs of fat maldistribution. Interventions A standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis. Main outcome measures Demographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy. Results Independent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use. Conclusions HIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.
Journal Article•
TL;DR: The present article reviews the recent advances in the diagnosis of preinvasive and early-invasive cancer to identify biomarkers for early detection of lung cancer and for chemoprevention studies.
Abstract: Lung cancer is the most common cause of cancer death in developed countries. The prognosis is poor, with less than 15% of patients surviving 5 years after diagnosis. The poor prognosis is attributable to lack of efficient diagnostic methods for early detection and lack of successful treatment for metastatic disease. Most patients (>75%) present with stage III or IV disease and are rarely curable with current therapies. Within the last decade, rapid advances in molecular biology, pathology, bronchology, and radiology have provided a rational basis for improving outcome. These advancements have led to a better documentation of morphological changes in the bronchial epithelium before development of clinical evident invasive carcinomas. This has changed our concept of lung carcinogenesis and emphasized the multistep carcinogenesis approach on several levels. Combined with the technical developments in bronchoscopic techniques, e.g., laser-induced fluorescence endoscope (LIFE) bronchoscopy, we now have improved methods to localize preinvasive and early-invasive bronchial lesions. With the LIFE bronchoscope, a new morphological entity (angiogenic squamous dysplasia) has been recognized, which might be an important biomarker and target for antiangiogenic chemopreventive agents. To reduce the mortality of lung cancer, these new technologies have been taken into the clinic in different scientific settings. The use of low-dose spiral computed tomography in the screening of a high-risk population has demonstrated the possibility of diagnosing small peripheral tumors that are not seen on conventional X-ray. A shift in the therapeutic paradigm from targeting advanced clinically manifest lung cancer toward asymptomatic preinvasive and early-invasive cancer is occurring. The present article reviews the recent advances in the diagnosis of preinvasive and early-invasive cancer to identify biomarkers for early detection of lung cancer and for chemoprevention studies.
TL;DR: In conclusion, inhibition of ICE represents a novel anti-inflammatory strategy for intestinal inflammation and is effective during experimental colitis in mice.
Abstract: IL-1β-converting enzyme (ICE; caspase-1) is the intracellular protease that cleaves the precursors of IL-1β and IL-18 into active cytokines. In the present study, the effect of ICE deficiency was evaluated during experimental colitis in mice. In acute dextran sulfate sodium-induced colitis, ICE-deficient (ICE KO) mice exhibited a greater than 50% decrease of the clinical scores weight loss, diarrhea, rectal bleeding, and colon length, whereas daily treatment with IL-1 receptor antagonist revealed a modest reduction in colitis severity. To further characterize the function of ICE and its role in intestinal inflammation, chronic colitis was induced over a 30-day time period. During this chronic time course, ICE KO mice exhibited a near complete protection, as reflected by significantly reduced clinical scores and almost absent histological signs of colitis. Consistently, colon shortening occurred only in dextran sulfate sodium-exposed wild-type mice but not in ICE KO mice. Protection was accompanied by reduced spontaneous release of the proinflammatory cytokines IL-18, IL-1β, and IFN-γ from total colon cultures. In addition, flow cytometric analysis of isolated mesenteric lymph node cells revealed evidence of reduced cell activation in ICE KO mice as evaluated by surface expression of CD3 CD69 and CD4 CD25. We conclude that inhibition of ICE represents a novel anti-inflammatory strategy for intestinal inflammation.
TL;DR: Once‐weekly PEG(40kd) IFN α‐2a was associated with a higher number of sustained virological responses compared with IFNalpha 3 times weekly in patients with chronic hepatitis C, but had a similar safety profile.
TL;DR: It is proposed that the double‐strand ends present in unintegrated cDNA promote apoptosis, as is known to be the case for chromosomal double-strand breaks, and cDNA circularization removes the pro‐apoptotic signal.
Abstract: Early after infection, the retroviral RNA genome is reverse transcribed to generate a linear cDNA copy, then that copy is integrated into a chromosome of the host cell. We report that unintegrated viral cDNA is a substrate for the host cell non-homologous DNA end joining (NHEJ) pathway, which normally repairs cellular double-strand breaks by end ligation. NHEJ activity was found to be required for an end-ligation reaction that circularizes a portion of the unintegrated viral cDNA in infected cells. Consistent with this, the NHEJ proteins Ku70 and Ku80 were found to be bound to purified retroviral replication intermediates. Cells defective in NHEJ are known to undergo apoptosis in response to retroviral infection, a response that we show requires reverse transcription to form the cDNA genome but not subsequent integration. We propose that the double-strand ends present in unintegrated cDNA promote apoptosis, as is known to be the case for chromosomal double-strand breaks, and cDNA circularization removes the pro-apoptotic signal.
TL;DR: In this article, the authors explored Lewin's concept of "force" and found support for the proposition that newspaper gatekeeping is influenced more by forces on the routine level of analysis than by individual staff writers' characteristics.
Abstract: Lewin's concept of “force” is explored in this study, which shows support for the proposition that newspaper gatekeeping is influenced more by forces on the routine level of analysis than by individual staff writers' characteristics. Newspaper stories about fifty Congressional bills were content analyzed, and two surveys were conducted of the stories' writers and of editors at their newspapers. No individual-level force was related to the quantity of coverage the bills received, whereas editors' aggregated assessment of bills' newsworthiness was positively related to quantity of bills' newspaper coverage.
TL;DR: The results strongly suggest that Nkx2.2 regulates the differentiation and/or maturation, but not the initial specification, of oligodendrocyte progenitors, and that overproduction of Nk X.2 protein in fibroblast cells can induce gene expression from the proteolipid protein promoter.
Abstract: Oligodendrocytes are derived from glial precursors that arise from the ventral neural tube early in development. In the developing chicken CNS, oligodendrocyte progenitors selectively express Nkx2.2 homeodomain transcription factor, raising the possibility that Nkx2.2 may directly regulate oligogliogenesis. In this study, we have examined Nkx2.2 expression in rodent glial precursors and studied the effect of a loss of Nkx2.2 on oligodendrocyte and astrocyte differentiation. We show that Nkx2.2 is also expressed in mammalian oligodendrocyte progenitors and that the differentiation of MBP-positive and PLP-DM20-positive oligodendrocytes is dramatically retarded in Nkx2.2-null mutants along the entire rostrocaudal axis. In contrast, no effect is seen on astrocytic differentiation. Interestingly, absence of Nkx2.2 expression leads to a ventral expansion of the Olig1/Olig2 expression in neuroepithelial cells into the Nkx2.2 domain and a consequent increase in the production of Olig1/Olig2-positive and platelet-derived growth factor receptor alpha-positive oligodendrocyte progenitors. These results strongly suggest that Nkx2.2 regulates the differentiation and/or maturation, but not the initial specification, of oligodendrocyte progenitors. Consistent with this suggestion, overproduction of Nkx2.2 protein in fibroblast cells can induce gene expression from the proteolipid protein promoter.
TL;DR: Fomepizole appears to be safe and effective in the treatment of methanol poisoning and nine patients survived and two patients who died had anoxic brain injury that was present at the time of enrollment.
Abstract: Background Methanol poisoning may result in metabolic acidosis, blindness, and death. The inhibition of alcohol dehydrogenase is fundamental to the treatment of methanol poisoning. We performed a multicenter study to evaluate fomepizole, an inhibitor of alcohol dehydrogenase, in the treatment of patients with methanol poisoning. Methods We administered intravenous fomepizole to 11 consecutive patients who presented with methanol poisoning at a participating center. Serial clinical and laboratory studies, including measurements of plasma formic acid and fomepizole, were performed. The outcomes measured were the preservation of visual acuity, the resolution of metabolic acidosis, the inhibition of formic acid production, the achievement of therapeutic plasma concentrations of fomepizole with the dosing regimen, residual illness or disability, and death. Results Plasma formic acid concentrations were detectable in eight patients, and these concentrations were closely correlated with the initial arterial pH v...
TL;DR: A role for L1 ORF1p is suggested in mediating nucleic acid strand transfer steps during L1 reverse transcription, promoting annealing of complementary DNA strands, and facilitating strand exchange to form the most stable hybrids in competitive displacement assays.
Abstract: Non-LTR retrotransposons such as L1 elements are major components of the mammalian genome, but their mechanism of replication is incompletely understood. Like retroviruses and LTR-containing retrotransposons, non-LTR retrotransposons replicate by reverse transcription of an RNA intermediate. The details of cDNA priming and integration, however, differ between these two classes. In retroviruses, the nucleocapsid (NC) protein has been shown to assist reverse transcription by acting as a “nucleic acid chaperone,” promoting the formation of the most stable duplexes between nucleic acid molecules. A protein-coding region with an NC-like sequence is present in most non-LTR retrotransposons, but no such sequence is evident in mammalian L1 elements or other members of its class. Here we investigated the ORF1 protein from mouse L1 and found that it does in fact display nucleic acid chaperone activities in vitro. L1 ORF1p (i) promoted annealing of complementary DNA strands, (ii) facilitated strand exchange to form the most stable hybrids in competitive displacement assays, and (iii) facilitated melting of an imperfect duplex but stabilized perfect duplexes. These findings suggest a role for L1 ORF1p in mediating nucleic acid strand transfer steps during L1 reverse transcription.
TL;DR: The results clearly indicate that the IT-leader firms have a higher level of IT management sophistication and a higher role for their IT-leaders compared to IT- enabled customer focus, IT-enabled operations focus, and IT-laggard firms.
Abstract: Recently,despite huge incentives and subsequent increases in investment in customer relationship management technology, many firms have not been able to increase their customer satisfaction index ratings. The purpose of this paper is to gauge whether IT management practices differ among firms where IT has a major role in transforming marketing, operations, or both, which give the firms advantage by affecting their customer service. Several research hypotheses are tested using data obtained from a survey of 213 IT-leaders in the financial services industry. The results clearly indicate that the IT-leader firms have a higher level of IT management sophistication and a higher role for their IT-leaders compared to IT-enabled customer focus, IT-enabled operations focus, and IT-laggard firms. This paper concludes with the implications for both researchers and practitioners.
TL;DR: In this article, the authors revisited their identity-based view of sustainable advantage by questioning their premise that it is possible to gain a sustainable advantage based on any particular core competency, no matter how inimitable.
TL;DR: The evolution of a multidisciplinary clinical pathway, coordinating the resources of a level 1 trauma center and directed by joint decision making between trauma surgeons and orthopedic traumatologists, has resulted in improved patient survival, with primary benefits in reducing early deaths from exsanguination and late deaths from multiple organ failure.
Abstract: Objective
To determine whether the evolution of the authors’ clinical pathway for the treatment of hemodynamically compromised patients with pelvic fractures was associated with improved patient outcome