Building Writing Identities: Integrating Explicit Strategies with Authentic Writing Experiences to Engage At-Promise Writers

The message of what constitutes good writing instruction, though promulgated for decades, has not always nor consistently trickled down to P–12 schools, where writing instruction is often focused on preparing students for success on standardized tests and where prescriptive and formulaic approaches to teaching writing are prevalent. Part of the reason for this might be that teachers are not always familiar enough with authentic writing experiences that adequately engage all learners. As scholars in the fields of literacy and special education, respectively, the authors combine their collective expertise to address this concern. They offer skills-based tools and strategies that can be integrated into authentic writing experiences to promote critical thinking and creativity, build students’ writing identities, and help at-promise learners gain and maintain writing momentum. A balanced approach that harmonizes different orientations and paradigms lends credibility to this piece as an example of what educators joining together to form a coalition for student support can look like. This article is positioned to bridge the divide between seemingly dichotomous perspectives. Through the strategies and ideas the authors share, teachers will be better equipped to give at-promise writers reasons to believe in themselves and their writerly capabilities

HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

Background: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10$54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At$150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV

Geochemistry of Carbonates on Mars: Implications for Climate History and Nature of Aqueous Environments

Ongoing research on martian meteorites and a new set of observations of carbonate minerals provided by an unprecedented series of robotic missions to Mars in the past 15 years help define new constraints on the history of martian climate with important crosscutting themes including: the CO_2 budget of Mars, the role of Mg-, Fe-rich fluids on Mars, and the interplay between carbonate formation and acidity. Carbonate minerals have now been identified in a wide range of localities on Mars as well as in several martian meteorites. The martian meteorites contain carbonates in low abundances (<1 vol.%) and with a wide range of chemistries. Carbonates have also been identified by remote sensing instruments on orbiting spacecraft in several surface locations as well as in low concentrations (2–5 wt.%) in the martian dust. The Spirit rover also identified an outcrop with 16 to 34 wt.% carbonate material in the Columbia Hills of Gusev Crater that strongly resembled the composition of carbonate found in martian meteorite ALH 84001. Finally, the Phoenix lander identified concentrations of 3–6 wt.% carbonate in the soils of the northern plains. The carbonates discovered to date do not clearly indicate the past presence of a dense Noachian atmosphere, but instead suggest localized hydrothermal aqueous environments with limited water availability that existed primarily in the early to mid-Noachian followed by low levels of carbonate formation from thin films of transient water from the late Noachian to the present. The prevalence of carbonate along with evidence for active carbonate precipitation suggests that a global acidic chemistry is unlikely and a more complex relationship between acidity and carbonate formation is present

Hydrologic and isotopic modeling of Alpine Lake Waiau, Mauna Kea, Hawai'i

Analysis of hydrologic, meteorologic, and isotopic data collected over 3 yr quantifies and explains the enormous variability and isotopic enrichment (δ18O = +16.9, δD = +50.0) of alpine Lake Waiau, a culturally and ecologically significant perched lake near the summit of Mauna Kea, Hawai'i. Further, a simple one-dimensional hydrologic model was developed that couples standard water budget modeling with modeling of δD and δ18O isotopic composition to provide daily predictions of lake volume and chemistry. Data analysis and modeling show that winter storms are the primary source of water for the lake, adding a distinctively light isotopic signature appropriate for high-altitude precipitation. Evaporation at the windy, dry summit is the primary loss mechanism for most of the year, greatly enriching the lake in heavy isotopes

JC Polyomavirus Uses Extracellular Vesicles To Infect Target Cells

The endemic human JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy in immune-suppressed patients. The mechanisms of virus infection in vivo are not understood because the major target cells for virus in the brain do not express virus receptors and do not bind virus. We found that JCPyV associates with extracellular vesicles (EVs) and can infect target cells independently of virus receptors. Virus particles were found packaged inside extracellular vesicles and attached to the outer side of vesicles. Anti-JCPyV antisera reduced infection by purified virus but had no effect on infection by EV-associated virus. Treatment of cells with the receptor-destroying enzyme neuraminidase inhibited infection with purified virus but did not inhibit infection by EV-associated virus. Mutant pseudoviruses defective in sialic acid receptor binding could not transduce cells as purified pseudovirions but could do so when associated with EVs. This alternative mechanism of infection likely plays a critical role in the dissemination and spread of JCPyV both to and within the central nervous system

Cost-Effectiveness of Genotype Testing for Primary Resistance in Brazil

Objective: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil. Design: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype). Methods: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US$13,400, genotype test cost of US $230, and primary resistance prevalence of 4.4$12,300. Results: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45,000 to$44,770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges. Conclusions: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil

Validation and Calibration of a Computer Simulation Model of Pediatric HIV Infection

Background: Computer simulation models can project long-term patient outcomes and inform health policy. We internally validated and then calibrated a model of HIV disease in children before initiation of antiretroviral therapy to provide a framework against which to compare the impact of pediatric HIV treatment strategies. Methods: We developed a patient-level (Monte Carlo) model of HIV progression among untreated children 1,300 untreated, HIV-infected African children. Results: In internal validation analyses, model-generated survival curves fit IeDEA data well; modeled and observed survival at 16 months of age were 91.2% and 91.1%, respectively. RMSE varied widely with variations in CD4% parameters; the best fitting parameter set (RMSE = 0.00423) resulted when CD4% was 45% at birth and declined by 6%/month (ages 0-3 months) and 0.3%/month (ages >3 months). In calibration analyses, increases in IeDEA-derived mortality risks were necessary to fit UNAIDS survival data. Conclusions: The CEPAC-Pediatric model performed well in internal validation analyses. Increases in modeled mortality risks required to match UNAIDS data highlight the importance of pre-enrollment mortality in many pediatric cohort studies

The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource

Background CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset. Methods Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies. Results Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation. Conclusions Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration

A Pre-mRNA–Associating Factor Links Endogenous siRNAs to Chromatin Regulation

In plants and fungi, small RNAs silence gene expression in the nucleus by establishing repressive chromatin states. The role of endogenous small RNAs in metazoan nuclei is largely unknown. Here we show that endogenous small interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in Caenorhabditis elegans. In addition, we report the identification and characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA–driven H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3, the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin association, but not NRDE-1/pre-mRNA association. These data establish that NRDE-1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct chromatin modifications via the Nrde pathway in C. elegans

Resource Utilization and Cost-Effectiveness of Counselor- vs. Provider-Based Rapid Point-of-Care HIV Screening in the Emergency Department

Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and$31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of$64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services