California ground squirrels (Spermophilus beecheyi) and northern Pacific rattlesnakes (Crotalus viridus oreganus) have an adversarial relationship. Adults are partially protected by venom resistance ...and harass rattlesnakes in part to defend their more vulnerable offspring. Larger, warmer snakes are more dangerous than smaller colder snakes, and in escalated conflict squirrels could benefit from risk assessment strategies. Rattlesnakes often rattle at harassing squirrels and rattling sounds produce cues related to body size and temperature. In study 1 we played back rattling sounds from snakes that varied in dangerousness and evaluated the roles of sex and parity in squirrel risk assessment strategies. In general, squirrels tail flagged and stood bipedally more, and were slower to reapproach the playback speaker following playbacks of rattling sounds from more dangerous snakes. In comparison with males and nonmothers, mothers were most responsive to rattling sounds and more sensitive to variation in snake dangerousness. Mothers tail flagged more than males and nonmothers, and this behavior tracked variation in snake dangerousness most closely, perhaps reflecting the effects of snake size and temperature on pup vulnerability. These findings suggest that many aspects of squirrel antisnake behavior are governed by their effects on descendant kin. In study 2 we tested the effects of offspring age on mothers’ responses to live rattlesnakes and rattling sounds. According to the offspring value hypothesis, mothers should take more risks in defense of older offspring because they are more likely to survive to reproductive age. By contrast, under the offspring vulnerability hypothesis, older offspring are less vulnerable to predators and thus mothers should take fewer risks. Risk-taking, as measured by behaviors that bring the squirrel close to the snake’s strike range, was either unaffected by or negatively correlated with offspring age. Thus, our findings suggest that whereas offspring value is unimportant in squirrel antisnake behavior, offspring vulnerability may affect maternal defense. We suggest that offspring vulnerability in mammals, in comparison with birds, may play a larger role in parental defense against predators.
To prospectively analyze the outcome of patients with Stage A neuroblastoma (NB) treated with surgery alone, especially with regard to the prognostic significance of age, tumor site, MYCN copy ...number, tumor cell ploidy, and histology.
The clinical course of 329 patients with Stage A disease registered on the POG NB Biology Study #9047 between February, 1990 and October, 1997 were evaluated. Age, tumor site, MYCN copy number, tumor cell ploidy, and histology were analyzed for their impact on event-free survival (EFS) and survival (S).
The 5-year estimated EFS and S rates for the 329 patients were 91% (+/-3%) and 96% (+/-2%), respectively. The EFS rate was similar for infants younger than 12 months and children age 12 months or older, but age older than 12 months was predictive of lower S rates (P = 0.044). Patients with adrenal, abdominal non-adrenal, thoracic, and cervical tumors had similar S rates. The majority of patients had tumors with favorable biologic features, and only 3% had MYCN amplification. For infants with diploid tumors, the EFS rate was 82% (+/-16%), but effective therapy yielded an S rate of 100%. Rate of S was 80% (+/-26%) and 64% (+/-27%) for patients with unfavorable tumor histology and MYCN-amplified tumors, respectively.
The outcome for patients with Stage A NB treated with surgery alone is excellent. Although EFS and S rates were significantly worse for patients with MYCN-amplified tumors, a subset achieved long-term remission after surgery alone. For patients with Stage A and MYCN amplification, additional factors are needed to distinguish the patients who will achieve long-term remission with surgery alone from those who will develop recurrent disease.
We propose that the predator–prey relationship between California ground squirrels,Spermophilus beecheyi beecheyi , and northern Pacific rattlesnakes, Crotalus viridis oreganus , offers a compelling ...analogy with the well-studied case of intraspecific fighting and assessment. Because ground squirrels frequently place themselves at risk by harassing rattlesnakes, they stand to benefit from assessment strategies which serve to mediate risk. For example, larger and warmer snakes are more dangerous than smaller and cooler ones. These determinants of dangerousness covary with acoustic characteristics of the rattling sounds elicited by squirrel harassment. To determine whether squirrels use these acoustic cues regarding rattlesnake body size and body temperature, we played back rattling and control sounds to individuals in a population of free-living squirrels. The squirrels clearly associated rattling sounds with rattlesnakes and proved capable of assessing both determinants of rattlesnake dangerousness on the basis of acoustic cues. Several features of squirrel behaviour covaried with these acoustic cues, including tail flagging, bipedal posture, and hesitancy to reapproach the area where the rattle was heard. Many of these behavioural differences were sustained for up to 10min postplayback.
Vascular endothelial growth factor (VEGF) has been shown previously to correlate with tumor growth and metastasis in an experimental model of anaplastic Wilms' tumor. The authors hypothesized that ...treatment with anti-VEGF antibodies would suppress both primary tumor growth and metastasis in this model.
Tumors were induced in the right kidneys of nude mice by the injection of cultured Wilms' tumor cells. After 1 week, anti-VEGF treatment was begun with injection of either vehicle or an anti-VEGF antibody intraperitoneally. Mice were killed after 4.5 weeks of treatment and tumor weights and the incidence of metastases evaluated.
Anti-VEGF treatment resulted in a greater than 95% reduction in tumor weight (P <.0001). Anti-VEGF treatment also abolished the establishment of lung metastases (40% in control animals, P <.003). Cessation of treatment resulted in rebound tumor growth.
Anti-VEGF therapy can suppress both primary tumor growth and the establishment of metastases in experimental anaplastic Wilms' tumor.
We present and compare AMS-
14C geochronologies for sediment cores recovered from Lake Titicaca, South America. Radiocarbon dates from three core sites constrain the timing of late Quaternary ...paleoenvironmental changes in the Central Andes and highlight the site-specific factors that limit the radiocarbon geochronometer. With the exception of mid-Holocene sediments, all cores are generally devoid of macrophyte fragments, thus bulk organic fractions are used to build core chronologies. Comparisons of radiocarbon results for chemically defined fractions (bulk decalcified, humate, humin) suggest that ages derived from all fractions are generally coherent in the post-13,500 yr BP time interval. In the pre-13,500 yr BP time interval, ages derived from humate extracts are significantly younger (300–7000 years) than ages from paired humin residues. Gross age incoherencies between paired humate and humin sub-fractions in pre-13,500 yr BP sediments from all core sites probably reflect the net downward migration of humates. Ages derived from bulk decalcified fractions at our shallow water (90 m) and deep water (230 m) core sites consistently fall between ages derived from humate and humin sub-fractions in the pre-13,500 yr BP interval, reflecting that the bulk decalcified fraction is predominantly a mixture of humate and humin sub-fractions. Bulk decalcified ages from the pre-13,500 yr BP interval at our intermediate depth core site (150 m) are consistently older than humate (youngest) and humin sub-fractions. This uniform, reproducible pattern can be explained by the mobilization of a relatively older organic sub-fraction during and after the re-acidification step following the alkaline treatment of the bulk sediment. The inferred existence of this ‘alkali-mobile, acid-soluble’ sub-fraction implies a different depositional/post-depositional history that is potentially associated with a difference in source material. While internally consistent geochronologies can be developed for the Lake Titicaca sequence using different organic fractions, mobile organic sub-fractions and fractions containing mobile sub-fractions should generally be avoided in geochronology studies. Consequently, we believe humin and/or bulk decalcified ages provide the most consistent chronologies for the post-13,500 yr BP interval, and humin ages provide the most representative ages for sedimentation prior to 13,500 yr BP interval.
Using the age model derived from the deep water core site and a previously published isotope-based lake-level reconstruction, we present a qualitative record of lake level in the context of several ice-core records from the western hemisphere. We find the latest Pleistocene lake-level response to changing insolation began during or just prior to the Bølling/Allerød period. Using the isotope-based lake-level reconstruction, we also find the 85-m drop in lake level that occurred during the mid-Holocene was synchronous with an increase in the variability of ice-core
δ
18O from a nearby icecap, but was not reflected in any of the polar ice-core records recovered from the interior of Antarctica and Greenland.
Study objective Corticosteroids (steroids) are often used to mitigate symptoms and prevent subsequent reactions in emergency department (ED) patients with allergic reactions, despite a lack of ...evidence to support their use. We sought to determine the association of steroid administration with improved clinical outcomes. Methods Adult allergy-related encounters to 2 urban EDs during a 5-year period were identified and classified as “anaphylaxis” or “allergic reaction.” Regional and provincial databases identified subsequent ED visits or deaths within a 7-day period. The primary outcome was allergy-related ED revisits in the steroid- and nonsteroid-exposed groups, adjusting for potential confounders with a propensity score analysis; secondary outcomes included the number of clinically important biphasic reactions and deaths. Results Two thousand seven hundred one encounters (473 anaphylactic) were included; 48% were treated with steroids. Allergy-related ED revisits occurred in 5.8% and 6.7% of patients treated with and without steroids, respectively (adjusted odds ratio OR 0.91; 95% confidence interval CI 0.64 to 1.28), with a number needed to treat (NNT) to benefit of 176 (95% CI NNT to benefit 39 to ∞ to NNT to harm 65). The adjusted OR in the anaphylaxis subgroup was 1.12 (95% CI 0.41 to 3.27). In the allergic reaction group, the adjusted OR was 0.91 (95% CI 0.63 to 1.31), with an NNT to benefit of 173 (95% CI NNT to benefit 38 to ∞ to NNT to harm 58). In the steroid and nonsteroid groups, there were 4 and 1 clinically important biphasic reactions, respectively. There were no deaths. Conclusion Among ED patients with allergic reactions or anaphylaxis, corticosteroid use was not associated with decreased relapses to additional care within 7 days.
Study objective Although the management and outcomes of emergency department (ED) patients with atrial fibrillation or flutter have been explored, such studies have typically excluded patients with ...acute underlying medical illnesses. We seek to describe the ED treatment and outcomes of these complex patients with atrial fibrillation or flutter. Methods This retrospective descriptive cohort study used an ECG database from 2 urban EDs to identify consecutive ED patients with an ECG demonstrating atrial fibrillation or flutter from January 1, 2009, to December 31, 2009. We categorized patients with atrial fibrillation or flutter as “complex” according to prespecified criteria and then grouped them as being managed with rate or rhythm control attempts, or not. The primary outcome was safety of rate or rhythm control, measured by whether patients had a predefined adverse event or not. The secondary outcome was the success of rate or rhythm control, defined as rate control decreasing the pulse rate by 20 beats/min and successful rhythm control, both within 4 hours of treatment initiation. Descriptive statistics were used to compare the 2 groups. Results Four hundred sixteen complex patients with atrial fibrillation or flutter were identified. Patients managed with rate or rhythm control were similar in all baseline characteristics and illness distribution to patients who were not managed in this manner. The 135 patients with attempted rate control (105) or rhythm control (30) had 55 adverse events (40.7%; 95% confidence interval CI 32.5% to 49.5%), whereas the 281 patients not managed with rate or rhythm control had 20 adverse events (7.1%; 95% CI 4.5% to 10.9%), for a risk difference of 33.6% (95% CI 24.3% to 42.5%) and a relative risk of 5.7 (95% CI 3.6 to 9.1). Twenty of 105 patients (19.1%; 95% CI 12.3% to 28.1%) were successfully rate controlled, whereas 4 of 30 (13.3%; 95% CI 4.4% to 31.6%) were successfully rhythm controlled. Conclusion In ED patients with complex atrial fibrillation or flutter, attempts at rate and rhythm control are associated with a nearly 6-fold higher adverse event rate than that for patients who are not managed with rate or rhythm control. Success rates of rate or rhythm control attempts appear low.
In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points ...of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.
We investigated whether the protection from graft-versus-host disease (GVHD) afforded by donor treatment with granulocyte colony-stimulating factor (G-CSF) could be enhanced by dose escalation. Donor ...treatment with human G-CSF prevented GVHD in the B6 → B6D2F1 murine model in a dose-dependent fashion, and murine G-CSF provided equivalent protection from GVHD at 10-fold lower doses. Donor pretreatment with a single dose of pegylated G-CSF (peg-G-CSF) prevented GVHD to a significantly greater extent than standard G-CSF (survival, 75% versus 11%, P < .001). Donor T cells from peg-G-CSF-treated donors failed to proliferate to alloantigen and inhibited the responses of control T cells in an interleukin 10 (IL-10)-dependent fashion in vitro. T cells from peg-G-CSF-treated IL-10-/- donors induced lethal GVHD; T cells from peg-G-CSF-treated wild-type (wt) donors promoted long-term survival. Whereas T cells from peg-G-CSF wt donors were able to regulate GVHD induced by T cells from control-treated donors, T cells from G-CSF-treated wt donors and peg-G-CSF-treated IL-10-/- donors did not prevent mortality. Thus, peg-G-CSF is markedly superior to standard G-CSF for the prevention of GVHD following allogeneic stem cell transplantation (SCT), due to the generation of IL-10-producing regulatory T cells. These data support prospective clinical trials of peg-G-CSF-mobilized allogeneic blood SCT. (Blood. 2004;103:3573-3581)
The Oligocene–Miocene Maikop Series is a world-class source rock responsible for much of the oil and gas found in the South Caspian Basin. It is composed of up to 3 km of marine mudstone, and ...contains a nearly continuous record of deposition during progressive tectonic closure of the basin as the Arabian Peninsula converged northward into Eurasia. Historically, the stratigraphy of this interval has been difficult to define due to the homogenous nature of the fine-grained, clay-dominated strata. Outcrop exposures in eastern Azerbaijan allow direct observation and detailed sampling of the interval, yielding a more comprehensive stratigraphic context and a more advanced understanding of syndepositional conditions in the eastern Paratethys Sea. Specifically, the present investigation reveals that coupling field-based stratigraphic characterization with geochemical analyses (e.g., bulk elemental geochemistry, Rock-Eval pyrolysis, bulk stable isotope geochemistry) yields a more robust understanding of internal variations within the Maikop Series. Samples from seven sections located within the Shemakha–Gobustan oil province reveal consistent stratigraphic and spatial geochemical trends. It is proposed that the Maikop Series be divided into three members based on these data along with lithostratigraphic and biostratigraphic data reported herein. When comparing Rupelian (Early Oligocene) and Chattian (Late Oligocene) strata, the Rupelian-age strata commonly possess higher TOC values, more negative δ
15N
tot values, more positive δ
13C
org values, and higher radioactivity relative to Chattian-age rocks. The trace metals Mo and V (normalized to Al) are positively correlated with TOC, with maximum values occurring at the Rupelian–Chattian boundary and overall higher average values in the Rupelian. Across the Oligocene–Miocene boundary, a slight drop in V/Al, Mo/Al ratios is observed, along with drops in %S and TOC. These results indicate that geochemical signatures of the Maikop Series are regional in nature, and furthermore that analogous fine-grained sections may be better characterized and subdivided using similar techniques. In general, geochemical indicators suggest that the basin was in limited communication with the Tethys Sea throughout the Oligocene–Early Miocene, with suboxic to anoxic conditions present during the Oligocene and to a lesser extent in the Miocene. This increased isolation was likely due to tectonic uplift to both the south and north of the study area, and greatly enhanced by global sea-level fluctuations. These data serve as the basis for a more detailed understanding of the tectonic evolution of the region, and support a standardized chemostratigraphic division of the important petroleum source interval.
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