Critical Habitat at the Crossroads: Responding to the G.W. Bush Administration\u27s Attacks on Critical Habitat Designation under the ESA

In this article, we argue that the George W. Bush Administration\u27s ( Administration ) attacks on the critical habitat protections in the Endangered Species Act ( ESA ) warrant priority attention from the environmental movement. Many species across the United States and, indeed, around the world, continue to slip towards extinction. As Congress recognized when it passed the ESA, the decline of most species can be directly traced to the destruction of their habitat. Protection and restoration of ecosystems that support endangered species is thus fundamental to species conservation

Influence of Comorbidities on Therapeutic Progression of Diabetes Treatment in Australian Veterans: A Cohort Study

BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84–0.91], P<0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS / SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.Agnes I. Vitry, Elizabeth E. Roughead, Adrian K. Preiss, Philip Ryan, Emmae N. Ramsay, Andrew L. Gilbert, Gillian E. Caughey, Sepehr Shakib, Adrian Esterman, Ying Zhang and Robyn A. McDermot

Modeling Teacher Ratings of Online Resources: A Human-Machine Approach to Quality

In education, the scalable deployment of media-rich online resources supports peer production in ways that promise to radically transform teaching and learning (CRA, 2005; Pea et al., 2008). Online educational repositories such as the Digital Library for Earth Systems Education (DLESE.org) and the National Science Digital Library (NSDL.org) collect and curate online learning resources created for a wide range of educational audiences and subject areas (McArthur & Zia, 2008). Through a simple, web-based authoring tool, called the Instructional Architect (IA.usu.edu) teachers locate and share educational resources and activities in an IA project. These IA projects can then be viewed, copied, and adapted by other IA users, in ways that support innovative teacher peer production. A vexing problem for such initiatives remains the elusive notion of quality. In peer production environments, how does one identify quality online content? Moreover, how does one do so in sustainable, cost-effective, and scalable ways? Previous work (Bethard, et al, 2009) presented an innovative approach for using machine learning models to automatically assess the quality and pedagogic utility of educational digital library resources. They demonstrated the feasibility and accuracy of automatic quality assessments for a single STEM domain and audience-level: high school Earth science. This work reports recent efforts to extend these models to support a broader range of STEM topics and grade levels, specifically applied to IA projects and compared model outputs to quality assessments made by K-12 teachers. Since the nature of the resources being compared in the IA (peer) versus DLESE (expert) are different, results of this study provide insights on the generalizability of this machine learning approach and its potential for facilitating teacher peer production

In vivo and in vitro characterization of the immune stimulating activity of the Neisserial porin PorB.

Vaccines play a vital role in modern medicine. The development of novel vaccines for emerging and resistant pathogens has been aided in recent years by the use of novel adjuvants in subunit vaccines. A deeper understanding of the molecular pathways behind adjuvanticity is required to better select immunostimulatory molecules for use in individual vaccines. To this end, we have undertaken a study of the essential signaling pathways involved in the innate and adaptive immune responses to the Neisseria meningitidis outer membrane protein Porin B (PorB). We have previously demonstrated that PorB is an agonist of Toll-Like Receptor 2 (TLR2) and acts as an adjuvant in vaccines for protein, carbohydrate and lipopolysaccharide antigens using murine models. Here we demonstrate NFκB translocation following stimulation with PorB only occurs in the presence of TLR2. IL-6 and TNF-α secretion was shown to be MAPK dependent. Surface expression of activation markers on macrophages, including CD40, CD69, and CD86, was increased following PorB stimulation in vitro. Interestingly, some upregulation of CD54 and CD69 was still observed in macrophages obtained from TLR2 KO mice, indicating a possible non-TLR2 mediated activation pathway induced by PorB. In a murine vaccination model, using ovalbumin as the antigen and PorB as the adjuvant, a decreased antigen-specific IgG production was observed in TLR2 KO mice; adjuvant-dependent increased IgG production was entirely ablated in MyD88 KO mice. These observations demonstrate the importance of the above pathways to the adjuvant activity of PorB. The potential TLR2 independent effect is currently being explored

The role of ender rodding in tibial fractures with an intact fibula

Thirty-three patients with tibia fractures and intact fibula were studied to determine the efficacy of Ender rod fixation in preventing a varus deformity of the tibia. Twenty-one patients were treated nonoperatively with five (23.8%) developing a significant varus angulation (greater than five degrees). No varus malunions were noted in those patients treated with Ender rods. Those patients treated with Ender rods and early weight-bearing had a shorter average time to union than those treated nonoperatively. We therefore feel that Ender rod fixation is a viable treatment modality in tibia fractures with an intact fibula. In these fractures the use of Ender rods helps prevent significant varus malunion and allows early weight-bearing, thus permitting early mobilization of the traumatized patient. © 1990 Raven Press, Ltd., New York

The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation

TOLL-like receptor (TLR) ligands activate both innate and adaptive immune cells, while modulating the cellular immune response. The outer membrane protein (OMP) from Neisseria meninigitidis, PorB, is a naturally occurring TLR2 ligand and functions as an adjuvant. Here, we demonstrate that PorB increases the level of OVA in the endo-/lysosomal cellular compartment of BMDCs, increases antigen presenting cell (APC) trafficking to draining lymph nodes, and enhances antigen cross-presentation. PorB is capable of mounting an antigen specific T cell response by efficiently stimulating antigen cross-presentation in vivo and in vitro assessed by BMDC OT-I cocultivation assays. The enhanced antigen cross-presentation and the increased APC recruitment to secondary lymphoid tissues expand the scope of known adjuvant effects of PorB on the immune system. Our findings lead to a better understanding of how TLR-ligand based adjuvants can alter and modulate immune responses

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

We investigated whether octogenarian patients with acute myeloid leukemia enrolled onto Cooperative Group clinical trials and treated with intensive induction therapy could be cured, and whether karyotype and selected molecular markers had any prognostic significance in these patients. Among 138 patients with cytogenetic information, normal karyotype was the most common (47.1%) followed by complex karyotype (14.5%) and sole +8 (9.4%). Among these patients, the relapse-free survival rate at 1 year was 37% and 13% at 3 years, and the respective overall survival rates were 24% and 8%. Whereas the 90 patients who survived beyond 30 days had the same relapse-free survival rates, their 1-year and 3-year overall survival rates were 36% and 11%,respectively. Of the 66 patients surviving beyond 30 days who could be classified into European LeukemiaNet genetic groups, those in the intermediate-I group had better overall survival than patients in the adverse group (P=0.01). Among patients with cytogenetically normal acute myeloid leukemia who were tested for the European LeukemiaNet-associated molecular alterations, FLT3-internal tandem duplication and NPM1 mutations, it was found that FLT3-internal tandem duplication (detected in 29% of patients) did not associate with overall survival (P=0.31),whereas NPM1 mutations (30%) were associated with a significantly longer overall survival (P=0.002). We conclude that intensive induction is effective and indicated in selected octogenarians with acute myeloid leukemia, that their overall survival varies among the European LeukemiaNet genetic groups and that NPM1 mutations may be of prognostic significance among octogenarian patients with cytogenetically normal acute myeloid leukemia

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

We investigated whether octogenarian patients with acute myeloid leukemia enrolled onto Cooperative Group clinical trials and treated with intensive induction therapy could be cured, and whether karyotype and selected molecular markers had any prognostic significance in these patients. Among 138 patients with cytogenetic information, normal karyotype was the most common (47.1%) followed by complex karyotype (14.5%) and sole +8 (9.4%). Among these patients, the relapse-free survival rate at 1 year was 37% and 13% at 3 years, and the respective overall survival rates were 24% and 8%. Whereas the 90 patients who survived beyond 30 days had the same relapse-free survival rates, their 1-year and 3-year overall survival rates were 36% and 11%,respectively. Of the 66 patients surviving beyond 30 days who could be classified into European LeukemiaNet genetic groups, those in the intermediate-I group had better overall survival than patients in the adverse group (P=0.01). Among patients with cytogenetically normal acute myeloid leukemia who were tested for the European LeukemiaNet-associated molecular alterations, FLT3-internal tandem duplication and NPM1 mutations, it was found that FLT3-internal tandem duplication (detected in 29% of patients) did not associate with overall survival (P=0.31),whereas NPM1 mutations (30%) were associated with a significantly longer overall survival (P=0.002). We conclude that intensive induction is effective and indicated in selected octogenarians with acute myeloid leukemia, that their overall survival varies among the European LeukemiaNet genetic groups and that NPM1 mutations may be of prognostic significance among octogenarian patients with cytogenetically normal acute myeloid leukemia