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41.
Global biodiversity in river and riparian ecosystems is generated and maintained by geographic variation in stream processes and fluvial disturbance regimes, which largely reflect regional differences in climate and geology. Extensive construction of dams by humans has greatly dampened the seasonal and interannual streamflow variability of rivers, thereby altering natural dynamics in ecologically important flows on continental to global scales. The cumulative effects of modification to regional-scale environmental templates caused by dams is largely unexplored but of critical conservation importance. Here, we use 186 long-term streamflow records on intermediate-sized rivers across the continental United States to show that dams have homogenized the flow regimes on third- through seventh-order rivers in 16 historically distinctive hydrologic regions over the course of the 20th century. This regional homogenization occurs chiefly through modification of the magnitude and timing of ecologically critical high and low flows. For 317 undammed reference rivers, no evidence for homogenization was found, despite documented changes in regional precipitation over this period. With an estimated average density of one dam every 48 km of third- through seventh-order river channel in the United States, dams arguably have a continental scale effect of homogenizing regionally distinct environmental templates, thereby creating conditions that favor the spread of cosmopolitan, nonindigenous species at the expense of locally adapted native biota. Quantitative analyses such as ours provide the basis for conservation and management actions aimed at restoring and maintaining native biodiversity and ecosystem function and resilience for regionally distinct ecosystems at continental to global scales.  相似文献   
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Objective: The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard. Methods: The COMPRESS consists of a combination of the Florida Surgical Questionnaire for Parkinson disease (FLASQ‐PD), a cognitive assessment battery provided by MindStreams® (NeuroTrax Corp.), and the Geriatric Depression Scale and the Zung Anxiety Self‐Assessment Scale. COMPRESS resulted in the classification of patients into three categories: “optimal candidate,”“probable candidate,” and “not a good candidate.” Similar categorical ratings made by a referring private practice neurologist and by a trained movement disorders specialist were compared with the ratings generated by COMPRESS. Results: A total of 19 subjects with Parkinson's disease were enrolled from five private neurological practices. The clinical impressions of the private practice neurologist vs. those of the movement disorders specialist were in agreement approximately half the time (10/19 cases). The movement disorders specialist and COMPRESS agreed on 15/19 cases. A further comparison between outcomes from the entire COMPRESS module and the FLASQ‐PD questionnaire by itself resulted in high agreement (18/19 cases in agreement). Conclusions: The COMPRESS agreed with an in‐person evaluation by a movement disorders neurologist approximately 80% of the time. The computerized COMPRESS did not provide any screening advantage over the short FLASQ‐PD paper questionnaire. Larger studies will be needed to assess the utility and cost effectiveness of this computerized triage method for DBS.  相似文献   
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PURPOSE: Soft tissue sarcoma (STS) is a rare heterogeneous malignancy. Overall survival has been stagnant for decades, primarily because systemic therapies are ineffective versus metastases, the leading cause of STS lethality. Consequently, we examined whether tyrosine kinase receptors active in STS growth signaling might be blockable and whether multireceptor blockade might synergize with low-dose STS chemotherapy by therapeutically affecting STS cells and their associated microenvironment. EXPERIMENTAL DESIGN: Vandetanib (AstraZenca), a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, was evaluated alone and with chemotherapy in vitro and in vivo in three human STS nude mouse xenograft models of different STS locations (muscle, uterus, lung), stages (primary, metastatic), and subtypes (leiomyosarcoma, fibrosarcoma, uterine sarcoma: luciferase-expressing MES-SA human uterine sarcoma cells surgically implanted into uterine muscularis with bioluminescence tumor growth assessment; developed by us). RESULTS: In vitro, human STS cells were sensitive to vandetanib. Vandetanib alone and with chemotherapy statistically significantly inhibited leiomyosarcoma local growth and fibrosarcoma lung metastasis. Direct injection of MES-SA into nude mice uterine muscularis resulted in high tumor take (88%), whereas s.c. injection resulted in no growth, suggesting microenvironmental tumor growth modulation. Vandetanib alone and with chemotherapy statistically significantly inhibited uterine sarcoma growth. In all models, vandetanib induced increased apoptosis, decreased tumor cell proliferation, and decreased angiogenesis. CONCLUSIONS: Vandetanib has antitumor effects against human STS subtypes in vitro and in vivo, where it also affects the tumor-associated microenvironment. Given the urgent need for better systemic approaches to STS, clinical trials evaluating vandetanib, perhaps with low-dose chemotherapy, seem warranted.  相似文献   
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OBJECTIVES: This study compared trends in adult cigarette smoking prevalence in California and the remainder of the United States between 1978 and 1994. METHODS: We used data from National Health Interview Surveys and Behavioral Risk Factor Surveillance System surveys to compare trends in smoking prevalence among persons 18 years and older. RESULTS: In both California and the remainder of the United States, the estimated annual rate of decline in adult smoking prevalence accelerated significantly from 1985 to 1990: to -1.22 percentage points per year (95% confidence interval [CI] = -1.51, -0.93) in California and to -0.93 percentage points per year (95% CI = -1.13, -0.73) in the remainder of the nation. The rate of decline slowed significantly from 1990 to 1994: to -0.39 percentage points per year (95% CI = -0.76, -0.03) in California and to -0.05 percentage points per year (95% CI = -0.34, 0.24) in the remainder of the United States. CONCLUSIONS: The presence of an aggressive tobacco control intervention has supported a significant decline in adult smoking prevalence in California from 1985 to 1990 and a slower but still significant decline from 1990 to 1994, a period in which there was no significant decline in the remainder of the nation. To restore nationwide progress in reducing smoking prevalence, other states should consider similar interventions.  相似文献   
47.
The turnover and pool size of surfactant has been studied in animals, but there is little similar information in humans. In the present investigation lung effluent phospholipids were studied in 29 small preterm infants with severe RDS. Thirteen were treated with mechanical ventilation, and 16 additionally received natural human surfactant. The first dose (60 mg surfactant/kg body wt) was given between 2 and 10 h of age, and the surfactant was given again if there was an insufficient response. Together 260 aspirates, recovered during routine suctioning of the airways, were analyzed for phospholipids. Phosphatidylglycerol, present only in exogenous surfactant, was used as a specific marker to estimate the apparent pool size and the half-life of surfactant phospholipid. In addition, the saturated phosphatidylcholine/sphingomyelin ratios were correlated with the ventilatory index (mean airway pressure X fractional inspiratory oxygen/arterial oxygen tension). There was a linear correlation between the ventilatory index and the saturated phosphatidylcholine/sphingomyelin (r approximately -0.70) but no consistent correlation between the ventilatory index and the amount of phospholipids in the aspirate. The saturated phosphatidylcholine/sphingomyelin ratio increased during the surfactant-induced remission of respiratory failure, decreased during the recovery. The control infants tended to have lower saturated phosphatidylcholine/sphingomyelin ratios during the first week than the surfactant-treated infants.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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Many biological interactions are multivalent, linking two particles via many copies of the same ligand-receptor binding pair. Examples of multivalent binding range from cell-cell adhesion to the assembly of large protein complexes from constituent multimers to the binding of AB5 bacterial toxins at the cell surface. Multivalent interactions can be effectively mimicked, inhibited, or disrupted through the design of suitable multivalent ligands. We review here recent work on multivalent ligand design based on a number of different chemical scaffolds, with a specific emphasis on the use of structure-based ligand design to target multimeric bacterial toxins.  相似文献   
50.
OBJECTIVE: Spatial compound sonography is a method that obtains sonographic information from several different angles of insonation and combines them to produce a single image. By reducing speckle and improving definition of tissue planes, this method can potentially improve image quality in musculoskeletal sonography. The purpose of our study was to compare real-time spatial compound sonography with conventional high-resolution musculoskeletal sonography. MATERIALS AND METHODS: Thirty-four patients underwent sonography of the musculoskeletal system for a variety of indications. All patients were evaluated using conventional high-resolution sonography and real-time spatial compound sonography performed with a 12-5-MHz multifrequency linear array transducer. Conventional images and compound images depicting the same musculoskeletal structure were obtained in pairs. A total of 118 images (59 image pairs) were randomly assorted and reviewed on a computer monitor by three experienced sonologists working independently. The reviewers were unaware of the type of images they were evaluating. Image quality was rated using a 5-point scale. The image parameters evaluated were definition of tissue planes, speckle, other noise, and image detail. RESULTS: Analysis of variance revealed that real-time spatial compound sonography significantly improved definition of soft-tissue planes, reduced speckle and other noise, and improved image detail when compared with conventional high-resolution sonography (p < 0.0001 for all evaluated parameters). CONCLUSION: Real-time spatial compound sonography significantly improved sonographic image quality in the musculoskeletal system when compared with conventional high-resolution sonography. Because musculoskeletal sonography is highly dependent on image quality and tissue-plane definition, spatial compound sonography represents an important development.  相似文献   
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