Designing data collection for decision-making: shaping the coastal First Nations regional monitoring system to meet the needs of the Nations

The Coastal First Nations (CFN) Regional Monitoring System (RMS) was redeveloped to support decisions related to threats to ecological and cultural values, resulting from changes to existing and impending resource use on the North and Central Coast of British Columbia. As First Nations reassert their governance authority, participate in shared decision-making with other governments, undertake land and marine use planning, and manage their territories and resources, the need for coordinated regional monitoring efforts are increasingly important. We used a systematic and inclusive strategy to determine a suitable monitoring approach to meet the needs of a diverse group of Nations across a broad geographic region. Linking data collection to decision-making and planning processes was central to our strategy. We began with engaging individuals at each Nation’s resource management office to gain a comprehensive understanding of the monitoring activities undertaken, the data being collected, the data desired, and the way data are used to support decision-making and planning processes. Concurrently, we worked with the member Nations to develop a decision-making framework to identify the monitoring activities best suited for the RMS based on the goals of the system. Applying the framework to the suite of monitoring activities being undertaken or desired resulted in a suite of monitoring activities that was further refined in a workshop with the Nations. We produced monitoring cards for each monitoring activity, which detail the monitoring research question(s), the data to collect, the sampling design and data collection protocols, and the decision-making and planning processes the data support. The RMS is designed to be adaptable as new priorities emerge. It is the only system of its kind on the coast of British Columbia, and it is increasingly looked to as a model for how First Nations-led monitoring programs can inform planning and decision-making processes

Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel

BACKGROUND: The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel. METHODS: The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2). RESULTS: Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis. CONCLUSIONS: Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment

Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice

Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how the absence of liver Lrp1 expression affects RVF pathogenesis. Mice lacking Lrp1 expression in hepatocytes showed minimal RVFV replication in the liver, longer time to death, and altered clinical signs toward neurological disease. In contrast, RVFV infection levels in other tissues showed no difference between the two genotypes. Therefore, Lrp1 is essential for RVF hepatic disease in mice

Expanding Efficiency: Women\u27s Communication in Engineering

As engineering fields strive to be more inclusive of women, focusing on perceptions of women\u27s work is vital to understanding how women can succeed and the limitations they may face. One area in need of more attention is the connection between communication and women\u27s experiences in engineering. This article examines the gendered nature of writing labor in engineering, focusing on case studies of three women who were able to use writing effectively, yet how communication emerged as a gendered form of labor subject to gendered perceptions. While these women\u27s communication skills led to professional success, their association with writing echoes a historical division, where writing is viewed as less valuable than technical knowledge. This division has the potential to disadvantage women who are asked to take on more writing-related tasks. In addition, their writing and communication are subject to gendered perceptions of being ‘chatty’ or blunt rather than effective or efficient. Articulating these perceptions and attitudes can lead to a breakdown of the binary between writing and technical labor as well as appropriately valuing the contributions women make in engineering through writing

Trivalent Adenovirus Type 5 HIV Recombinant Vaccine Primes for Modest Cytotoxic Capacity That Is Greatest in Humans with Protective HLA Class I Alleles

If future HIV vaccine design strategies are to succeed, improved understanding of the mechanisms underlying protection from infection or immune control over HIV replication remains essential. Increased cytotoxic capacity of HIV-specific CD8+ T-cells associated with efficient elimination of HIV-infected CD4+ T-cell targets has been shown to distinguish long-term nonprogressors (LTNP), patients with durable control over HIV replication, from those experiencing progressive disease. Here, measurements of granzyme B target cell activity and HIV-1-infected CD4+ T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5) HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP. We observed readily detectable HIV-specific CD8+ T-cell recall cytotoxic responses in vaccinees at a median of 331 days following the last immunization. The magnitude of these responses was not related to the number of vaccinations, nor did it correlate with the percentages of cytokine-secreting T-cells determined by ICS assays. Although the recall cytotoxic capacity of the CD8+ T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection. These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8+ T-cell cytotoxic responses

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility