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81.
Climate change will affect not only natural and cultural resources within protected areas but also tourism and visitation patterns. The U.S. National Park Service systematically collects data regarding its 270+ million annual recreation visits, and therefore provides an opportunity to examine how human visitation may respond to climate change from the tropics to the polar regions. To assess the relationship between climate and park visitation, we evaluated historical monthly mean air temperature and visitation data (1979–2013) at 340 parks and projected potential future visitation (2041–2060) based on two warming-climate scenarios and two visitation-growth scenarios. For the entire park system a third-order polynomial temperature model explained 69% of the variation in historical visitation trends. Visitation generally increased with increasing average monthly temperature, but decreased strongly with temperatures > 25°C. Linear to polynomial monthly temperature models also explained historical visitation at individual parks (R2 0.12-0.99, mean = 0.79, median = 0.87). Future visitation at almost all parks (95%) may change based on historical temperature, historical visitation, and future temperature projections. Warming-mediated increases in potential visitation are projected for most months in most parks (67–77% of months; range across future scenarios), resulting in future increases in total annual visits across the park system (8–23%) and expansion of the visitation season at individual parks (13–31 days). Although very warm months at some parks may see decreases in future visitation, this potential change represents a relatively small proportion of visitation across the national park system. A changing climate is likely to have cascading and complex effects on protected area visitation, management, and local economies. Results suggest that protected areas and neighboring communities that develop adaptation strategies for these changes may be able to both capitalize on opportunities and minimize detriment related to changing visitation.  相似文献   
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The level of cyclic nucleotides in three populations of cultured human lymphocytes were studied. An early conspicuous elevation of c-GMP level and a reciprocal relationship between c-AMP and c-GMP fluctuations were demonstrated in T cells from normal donors. Null cells from patients with ALL showed a constantly low level of c-AMP, while c-GMP fluctuated in apparent relationship with cell doubling time. Persistently low levels of c-AMP and persistently high level of c-GMP were found in B cells from patients with CLL. Possible significance of these findings is discussed.  相似文献   
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Background

Most patients with metastatic non-small cell lung cancer (NSCLC) will face treatment with systemic therapy. Current clinical studies are demonstrating improvements in chemotherapy and overall survival. However, it remains unclear whether these results are translated into clinical practice.

Methods

We reviewed all stage IV NSCLC patients without second malignancies that were diagnosed from 2004 to 2006 at our institution. 493 consecutive patients were included into this retrospective analysis and were followed-up until end of 2011.

Results

352 patients (71.4%) received systemic therapy for up to 7 lines. For most patients, adjustments of dosages or applications had to be made at some point of the treatment, but the total applied dose remained generally close to the intended dose. The best disease control (BDC) rate decreased with increasing therapy lines from 59.7% to about 35%. Patients with palliative local therapy but no systemic treatment demonstrated inferior survival (median 2.9 versus 8.7 months, p < 0.001). The median interval between last treatment and death was 50 days and 15 days for chemotherapy and anti-EGFR therapy, respectively. BDC to the previous therapy lines was predictive for improved BDC to third- but not second-line therapy. Performing multivariate analysis, BDC to previous therapy, never-/ former-smoking status, and age > 70 years were associated with improved survival performing third-line therapy.

Conclusions

Stage IV NSCLC patients may receive substantial systemic therapy resulting in response and median survival rates that are comparable to data from clinical studies. However, preselection factors are increasingly important to improve therapy outcome and life quality.  相似文献   
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Contrary to expectation, populations of clonal organisms are often genetically highly diverse. In phytoplankton, this diversity is maintained throughout periods of high population growth (that is, blooms), even though competitive exclusion among genotypes should hypothetically lead to the dominance of a few superior genotypes. Genotype-specific parasitism may be one mechanism that helps maintain such high-genotypic diversity of clonal organisms. Here, we present a comparison of population genetic similarity by estimating the beta-dispersion among genotypes of early and peak bloom populations of the diatom Asterionella formosa for three spring-blooms under high or low parasite pressure. The Asterionella population showed greater beta-dispersion at peak bloom than early bloom in the 2 years with high parasite pressure, whereas the within group dispersion did not change under low parasite pressure. Our findings support that high prevalence parasitism can promote genetic diversification of natural populations of clonal hosts.  相似文献   
87.
Resource managers at parks and other protected areas are increasingly expected to factor climate change explicitly into their decision making frameworks. However, most protected areas are small relative to the geographic ranges of species being managed, so forecasts need to consider local adaptation and community dynamics that are correlated with climate and affect distributions inside protected area boundaries. Additionally, niche theory suggests that species'' physiological capacities to respond to climate change may be underestimated when forecasts fail to consider the full breadth of climates occupied by the species rangewide. Here, using correlative species distribution models that contrast estimates of climatic sensitivity inferred from the two spatial extents, we quantify the response of limber pine (Pinus flexilis) to climate change in Rocky Mountain National Park (Colorado, USA). Models are trained locally within the park where limber pine is the community dominant tree species, a distinct structural-compositional vegetation class of interest to managers, and also rangewide, as suggested by niche theory. Model forecasts through 2100 under two representative concentration pathways (RCP 4.5 and 8.5 W/m2) show that the distribution of limber pine in the park is expected to move upslope in elevation, but changes in total and core patch area remain highly uncertain. Most of this uncertainty is biological, as magnitudes of projected change are considerably more variable between the two spatial extents used in model training than they are between RCPs, and novel future climates only affect local model predictions associated with RCP 8.5 after 2091. Combined, these results illustrate the importance of accounting for unknowns in species'' climatic sensitivities when forecasting distributional scenarios that are used to inform management decisions. We discuss how our results for limber pine may be interpreted in the context of climate change vulnerability and used to help guide adaptive management.  相似文献   
88.
Limb venous compliance decreases with advancing age, even in healthy humans. To test the hypothesis that adrenergic mechanisms contribute to age-associated reductions in limb venous compliance, we measured calf venous compliance before and during acute systemic α- and β-adrenergic blockade in eight young (27 ± 1 yr old, mean ± SE) and eight older healthy men (67 ± 2 yr old). Calf venous compliance was determined in supine subjects by inflating a thigh-collecting cuff to 60 mmHg for 8 min and then decreasing it (1 mmHg/s) to 0 mmHg while calf volume was indexed with a strain gauge. The slope (·10?3) of the pressure-compliance relation (compliance= β? + 2·β?·cuff pressure), which is the first derivative of the quadratic pressure-volume relation [(Δlimb volume) = β?+ β?·(cuff pressure) + β?·(cuff pressure)2] during reductions in cuff pressure, was used to quantify calf venous compliance. Calf venous compliance was ~30% lower (P < 0.01) in older compared with young men before adrenergic blockade. In response to adrenergic blockade calf venous compliance did not increase in young (-2.62 ± 0.14 and -2.29 ± 0.18 ml·dl?1·mmHg?1, before and during blockade, respectively) or older men (-1.78 ± 0.27 and -1.68 ± 0.21 ml·dl?1 ·mmHg?1). Moreover, during adrenergic blockade differences in calf venous compliance between young and older men observed before adrenergic blockade persisted. Collectively, these data strongly suggest that adrenergic mechanisms neither directly restrain calf venous compliance in young or older men nor do they contribute to age-associated reductions in calf venous compliance in healthy men.  相似文献   
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MOTIVATION: The sensitivity and specificity of branched DNA (bDNA) assays are derived in part through the judicious design of the capture and label extender probes. To minimize non-specific hybridization (NSH) events, which elevate assay background, candidate probes must be computer screened for complementarity with generic sequences present in the assay. RESULTS: We present a software application which allows for rapid and flexible design of bDNA probesets for novel targets. It includes an algorithm for estimating the magnitude of NSH contribution to background, a mechanism for removing probes with elevated contributions, a methodology for the simultaneous design of probesets for multiple targets, and a graphical user interface which guides the user through the design steps. AVAILABILITY: The program is available as a commercial package through the Pharmaceutical Drug Discovery program at Chiron Diagnostics.  相似文献   
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