159 research outputs found

    Factors influencing awareness of community-based shorebird conservation projects in Australia

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    We examine the awareness of potential volunteers (n = 360) living near nine community-based shorebird conservation projects. About half of the people sampled (54%) were unaware of the nearest project. Awareness of interviewees varied substantially among projects (28-78%). Apart from gaining awareness of projects through membership of natural history groups (43%), many respondents heard of projects through friends and relatives (20%), rather than through media such as newspapers (14%) and television (2.3%). We demonstrate that community-based projects can be quantitatively and critically assessed for awareness. The use of rapid, cost-effective assessments of awareness levels has application in many conservation projects. <br /

    Inductively coupled plasma mass spectrometric detection for multielement flow injection analysis and elemental speciation by reversed-phase liquid chromatography

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    The feasibility of using an inductively coupled plasma mass spectrometer as a muitieiement detector for flow injection analysis (FIA) and ion-pair reversed-phase liquid chromatography was investigated. Sample introduction was by uitrasonk nebulization with aerosol desolvation. Absolute detecton limits for FIA ranged from 0.01 to 0.1 ng for most elements using 10-pL injections. Over 30 elements were surveyed for their response to both anionic and cationic ion pairing reagents. The separation and selective detection of various As and Se species were demonstrated, yielding detection limits near 0.1 ng (as element) for ail six species present. Determination of 15 elements in a single injection with multiple ion monitoring produced shniiar detection limits. Isotope ratios were measured with sufficient precision (better than 2%) and accuracy (about 1 %) on eluting peaks of Cd and Pb to demonstrate that liquid chromatographyhductively coupled plasma mass spectrometry should make speciation studies with stable tracer isotopes feasible

    Functional loss of IKBE leads to NF-KB deregulation in aggressive chronic lymphocytic leukemia

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    NF-?B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-?B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I?B?, a negative regulator of NF-?B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I?B? protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I?B? loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-?B deregulation during lymphomagenesis. <br/

    Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

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    Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months
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