THE DESIGN AND IMPLEMENTATION OF AN INTERVENTION TO SUPPORT AND RETAIN EARLY CAREER MATHEMATICS TEACHERS

This study reports on efforts over several years to design and implement a yearlong intervention intended to support secondary mathematics teachers in their early years of teaching. The intervention is designed to support these teachers’ development of meaningful professional relationships with a school-based mentor and to create an online community of practice for support with other professionals. The intervention itself consists of early career teachers and their mentors participating in monthly professional development sessions such as online meetings, Zoom panels with experts, and collaboratively reading and discussing timely, purposeful, and relevant content. The intervention is designed to not over burden the participants and to be feasible for national implementation with little funding. The goal of the intervention is to try to retain secondary mathematics teachers in the profession by providing them with meaningful and targeted support Half of all teachers leave the profession within the first five years, and this rate is highest for mathematics positions in high poverty schools (Fantilli & McDougall, 2009; Goldring et al., 2014). Furthermore, half of all current teachers in the U.S. retiring in the next five years (Foster, 2010), enrollment in teacher preparation programs declining, and teacher turnover is costing America $7.3 billion annually (National Math + Science Initiative, 2013), which represents a crisis for public education in the U.S. These conditions lead to classrooms staffed with underprepared/unqualified teachers, which profoundly affects the mathematical preparation of students in high school, college, and beyond. Experts agree that addressing the mathematics-teaching crisis meaningfully will require building a more cohesive system of teacher preparation, support, and development (Mehta, TheisenHomer, Braslow, & Lopatin 2015). The purpose of this study is to report on the design and implementation of a cost effective, easily replicable intervention for early career secondary mathematics teachers with the goal of positively impacting teacher retention. We also present lessons learned over two years of implementing the intervention and provide suggestions for future research

Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses

Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH4Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC50 of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents

Effectiveness of inactivated influenza vaccines in preventing influenza-associated deaths and hospitalizations among Ontario residents aged ≥ 65 years: estimates with generalized linear models accounting for healthy vaccinee effects.

BACKGROUND: Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications. METHODS: We conducted a retrospective cohort study among Ontario residents aged ≥ 65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥ 65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations. RESULTS: During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥ 65 years was 22% (95% confidence interval [CI], -6%-42%) for all influenza-associated deaths, 25% (95% CI, 13%-37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%-31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively. CONCLUSIONS: By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ~4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario

Improving the Measurement of Health System Performance across the Rural-Urban Continuum

Introduction We report on key performance indicators to highlight quality and variation in health care. Given Ontario’s diverse geography, we have prioritized improving measurement across the rural-urban continuum. This will improve our ability to discern the impact of geography on health care and health status to inform planning and decision making. Objectives and Approach Building on previous work to advance measurement of equity in health care, we struck a technical working group of experts to review methods for stratifying health system performance data by geographic location in the Ontario context. These methods were applied to a set of key performance indicators. The working group’s review of the results of this analysis will lead to recommendations for the best method to refine and standardize how geographic location is measured and stratified. This will improve our ability to discern the impact of geography on health system performance and health status for our suite of public-reporting products. Results The technical working group identified three methodologies for consideration that used linked postal code data: Population Centre (POPCTR), Statistical Area Classification (SAC) and a hybrid POPCTR/SAC methodology. These methods were tested against a set of key performance indicators across dimensions of quality including timeliness, effectiveness, population health and health outcomes. The results show that, in the health system performance dimensions of effectiveness and timeliness, as well as for a subset of health outcomes, there is variation in performance across the urban-rural continuum, though not always in a linear way. This may reflect differences in health care access, health risk factors, sociodemographic or socioeconomic characteristics across the urban-rural continuum. More definitive conclusions and recommendations will be available when the working group meets to review the results. Conclusion/Implications Identifying a robust methodology for measuring performance across geographic locations will improve our ability to discern the impact of geography on health care including where geography may impact access and effectiveness of services as well as health outcomes. This information will enable better health system planning and decision-making

A sensitive one-step real-time PCR for detection of avian influenza viruses using a MGB probe and an internal positive control

BACKGROUND: Avian influenza viruses (AIVs) are endemic in wild birds and their introduction and conversion to highly pathogenic avian influenza virus in domestic poultry is a cause of serious economic losses as well as a risk for potential transmission to humans. The ability to rapidly recognise AIVs in biological specimens is critical for limiting further spread of the disease in poultry. The advent of molecular methods such as real time polymerase chain reaction has allowed improvement of detection methods currently used in laboratories, although not all of these methods include an Internal Positive Control (IPC) to monitor for false negative results. Therefore we developed a one-step reverse transcription real time PCR (RRT-PCR) with a Minor Groove Binder (MGB) probe for the detection of different subtypes of AIVs. This technique also includes an IPC. METHODS: RRT-PCR was developed using an improved TaqMan technology with a MGB probe to detect AI from reference viruses. Primers and probe were designed based on the matrix gene sequences from most animal and human A influenza virus subtypes. The specificity of RRT-PCR was assessed by detecting influenza A virus isolates belonging to subtypes from H1–H13 isolated in avian, human, swine and equine hosts. The analytical sensitivity of the RRT-PCR assay was determined using serial dilutions of in vitro transcribed matrix gene RNA. The use of a rodent RNA as an IPC in order not to reduce the efficiency of the assay was adopted. RESULTS: The RRT-PCR assay is capable to detect all tested influenza A viruses. The detection limit of the assay was shown to be between 5 and 50 RNA copies per reaction and the standard curve demonstrated a linear range from 5 to 5 × 10(8 )copies as well as excellent reproducibility. The analytical sensitivity of the assay is 10–100 times higher than conventional RT-PCR. CONCLUSION: The high sensitivity, rapidity, reproducibility and specificity of the AIV RRT-PCR with the use of IPC to monitor for false negative results can make this method suitable for diagnosis and for the evaluation of viral load in field specimens

Utilizing population-based clinical and administrative data to explore the relevance of frailty to cholinesterase inhibitor use and discontinuation at nursing home transition.

Introduction Cholinesterase inhibitors (ChEIs) are medications used to treat cognitive symptoms associated with Alzheimer’s disease. Previous studies examining the determinants of continued use or withdrawal of ChEIs during the transition into a nursing home have lacked detailed clinical information needed to understand the range of factors associated with pharmacotherapeutic decision-making. Objectives and Approach Population-based clinical and administrative health databases were linked to examine patterns of ChEI use among 47,851 adults (aged 66+) with dementia newly admitted to nursing homes in Ontario between April 2011-March 2015. We examined whether resident frailty, among other factors, was associated with ChEI discontinuation in the following year. Frailty was calculated using a validated 72-item index derived from the Resident Assessment Instrument (RAI-MDS 2.0). Discontinuation was defined as a 30-day period when no dispensations occurred and no supply of ChEI was available. Subdistribution hazard models estimated the association between resident characteristics and discontinuation, accounting for competing risk of death. Results Over one-third (36.7%) of residents were receiving a ChEI at admission and this proportion was lower among those defined as frail (33.6%) vs. non-frail (40.7%) at admission. Among those on a ChEI at admission, 82.3% continued use and 17.7% discontinued during the following year. After accounting for resident characteristics, ChEI type and previous use, the incidence of discontinuation was 15% higher in frail residents vs. non-frail residents (hazard ratio (HR)= 1.15, 95\% confidence interval (CI) [1.01,1.30]). Residents with severe aggressive behaviours (HR=1.82, 95% CI [1.60, 2.07]), and higher levels of cognitive impairment (HR=1.29, 95% CI [1.10, 1.51]) were more likely to discontinue. Residents aged 85+ (HR=0.69, 95% CI [0.61, 0.77]) and those who were widowed (HR=0.84, 95% CI [0.77, 0.91]) were less likely to discontinue. Conclusion/Implications Most residents who entered on a ChEI continued treatment during follow-up. The availability of linked clinical and administrative data allowed for a novel exploration of predictors of ChEI discontinuation. Frailty, severity of cognitive impairment and aggressive behaviours were associated with ChEI discontinuation; whereas selected sociodemographic factors predicted continued use

Using routinely collected laboratory and health administrative data to assess influenza vaccine effectiveness: introducing the Flu and Other Respiratory Viruses Research (FOREVER) Cohort

Introduction Annual evaluation of influenza vaccine effectiveness (VE) is required because of frequent changes to circulating and vaccine strains. Traditionally, VE studies enroll patients who fulfill case definitions for respiratory infections and are tested for influenza. VE estimates generated from convenience samples of routinely collected specimens might be biased. Objectives and Approach We assessed the validity of using data from respiratory specimens collected during clinical encounters to estimate VE. We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking respiratory virus laboratory test results from 2009-2014 from 11 public health and 8 hospital laboratories across Ontario to health administrative databases, including databases with billing claims for physician- and pharmacist-administered influenza vaccines. We evaluated the presence of information and selection biases when using these data and estimated VE in community-dwelling older adults (>65) using the test-negative design under conditions that emulated the inclusion criteria in traditional VE studies. Results The FOREVER Cohort included test results from 283,711 respiratory specimens obtained from 216,730 individuals. The overall linkage proportion to health administrative databases using deterministic and probabilistic linkage methods was 97.5%. Influenza positivity for older adults with unknown lag between illness onset and specimen collection was similar to those for whom illness onset date was documented to be ≤7 days before specimen collection, suggesting minimal outcome misclassification associated with information bias. The likelihood of influenza testing was similar between vaccinated and unvaccinated individuals, suggesting an absence of selection bias that could arise when a case definition for influenza testing is not employed. Lastly, VE estimates were similar under various conditions, demonstrating the robustness of using these data, and were comparable to published estimates. Conclusion/Implications The FOREVER Cohort can be used to estimate VE with negligible bias. Compared to traditional VE studies that are limited to recruited patients, routinely collected specimens create a larger, more generalizable sample. Linkage to health administrative databases can identify those with comorbidities and permit evaluation of VE in high-risk groups

The Function and Evolution of C2H2 Zinc Finger Proteins and Transposons

Transcription factors (TFs) confer specificity to transcriptional regulation by binding specific DNA sequences and ultimately affecting the ability of RNA polymerase to transcribe a locus. The C2H2 zinc finger proteins (C2H2 ZFPs) are a TF class with the unique ability to diversify their DNA-binding specificities in a short evolutionary time. C2H2 ZFPs comprise the largest class of TFs in Mammalian genomes, including nearly half of all Human TFs (747/1,639). Positive selection on the DNA-binding specificities of C2H2 ZFPs is explained by an evolutionary arms race with endogenous retroelements (EREs; copy-and-paste transposable elements), where the C2H2 ZFPs containing a KRAB repressor domain (KZFPs; 344/747 Human C2H2 ZFPs) are thought to diversify to bind new EREs and repress deleterious transposition events. However, evidence of the gain and loss of KZFP binding sites on the ERE sequence is sparse due to poor resolution of ERE sequence evolution, despite the recent publication of binding preferences for 242/344 Human KZFPs. The goal of my doctoral work has been to characterize the Human C2H2 ZFPs, with specific interest in their evolutionary history, functional diversity, and coevolution with LINE EREs. I contributed to the expert curation of the full complement of 1,639 Human TFs and used the results to quantitatively compare their evolutionary history and tissue specificities to all other Human TFs. I analyzed protein-protein interaction (PPI) data for 118 DNA-binding C2H2 ZFPs and found extremely diverse interactions with nuclear factors despite paradoxically few dedicated PPI domains, revealing a new and unexplained dimension of functional diversity in addition to DNA-binding specificity diversity. Finally, I pioneered a computational technique to reconstruct extinct LINE L1 sequences and showed that they can be used to anchor the integration of KZFP genomic binding data and binding specificities for a complete picture of dynamic KZFP-ERE sequence specificity relationships. Together, my results paint a detailed picture of the diverse functionality and rapid evolution of Human C2H2 ZFPs, contribute to ongoing theorization on KZFP-ERE coevolution, and provide parallel datasets to power future investigations.Ph.D