Boosting Reading Scores by Adding in Technology Based Interventions

The purpose of this action research project was to determine if adding a technology based literacy apps in a general education second grade classroom could increase the reading scores of the Informal Decoding Inventory that was given to second grade students, throughout a four month period to check personal growth. It will also look at other reading assessments in reading throughout the time frame, but for the purpose and time of this project the researcher will strictly be looking at growth through the inventory. Technology enriched phonemic awareness with a focus on decoding words, recognizing word patterns and fluency interventions and apps were provided weekly over a period of two months. Data was collected through qualitative observations and quantitative Decoding Inventory scores. Analysis of the data collected suggests that second grade student’s word decoding scores increased when students were introduced to technology based interventions

Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma

Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients

Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy1,2,3. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations2. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes1,3. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1)1,3,4. Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.This work was supported by an Alex's Lemonade Stand Young Investigator Award (S.C.M.), The CIHR Banting Fellowship (S.C.M.), The Cancer Prevention Research Institute of Texas (S.C.M., RR170023), Sibylle Assmus Award for Neurooncology (K.W.P.), the DKFZ-MOST (Ministry of Science, Technology & Space, Israel) program in cancer research (H.W.), James S. McDonnell Foundation (J.N.R.) and NIH grants: CA154130 (J.N.R.), R01 CA169117 (J.N.R.), R01 CA171652 (J.N.R.), R01 NS087913 (J.N.R.) and R01 NS089272 (J.N.R.). R.C.G. is supported by NIH grants T32GM00725 and F30CA217065. M.D.T. is supported by The Garron Family Chair in Childhood Cancer Research, and grants from the Pediatric Brain Tumour Foundation, Grand Challenge Award from CureSearch for Children’s Cancer, the National Institutes of Health (R01CA148699, R01CA159859), The Terry Fox Research Institute and Brainchild. M.D.T. is also supported by a Stand Up To Cancer St. Baldrick’s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113)

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Diatom Transcriptional and Physiological Responses to Changes in Iron Bioavailability across Ocean Provinces

Changes in iron (Fe) bioavailability influence diatom physiology and community composition, and thus have a profound impact on primary productivity and ecosystem dynamics. Iron limitation of diatom growth rates has been demonstrated in both oceanic and coastal waters of the Northeast Pacific Ocean and is predicted to become more pervasive in future oceans. However, it is unclear how the strategies utilized by phytoplankton to cope with low Fe bioavailability and resupply differ across these ocean provinces. We investigated the response of diatom communities to variable Fe conditions through incubation experiments performed in the Fe mosaic of the California Upwelling Zone and along a natural Fe gradient in the Northeast Pacific Ocean. Through coupling gene expression of two dominant diatom taxa (Pseudo-nitzschia and Thalassiosira) with biological rate process measurements, we provide an in-depth examination of the physiological and molecular responses associated with varying Fe status. Following Fe enrichment, oceanic diatoms showed distinct differential expression of gene products involved in nitrogen assimilation, photosynthetic carbon fixation, and vitamin production compared to diatoms from low-Fe coastal sites, possibly driven by the chronic nature of Fe stress at the oceanic site. Genes of interest involved in Fe and N metabolism additionally exhibited divergent expression patterns between the two diatom taxa investigated, demonstrating that diverse diatoms may invoke alternative strategies when dealing with identical changes in their environment. We report here several mechanisms used distinctly by coastal or oceanic diatom communities as well as numerous taxa-specific strategies for coping with Fe stress and rearranging nutrient metabolism following Fe enrichment

Image1.PDF

<p>Changes in iron (Fe) bioavailability influence diatom physiology and community composition, and thus have a profound impact on primary productivity and ecosystem dynamics. Iron limitation of diatom growth rates has been demonstrated in both oceanic and coastal waters of the Northeast Pacific Ocean and is predicted to become more pervasive in future oceans. However, it is unclear how the strategies utilized by phytoplankton to cope with low Fe bioavailability and resupply differ across these ocean provinces. We investigated the response of diatom communities to variable Fe conditions through incubation experiments performed in the Fe mosaic of the California Upwelling Zone and along a natural Fe gradient in the Northeast Pacific Ocean. Through coupling gene expression of two dominant diatom taxa (Pseudo-nitzschia and Thalassiosira) with biological rate process measurements, we provide an in-depth examination of the physiological and molecular responses associated with varying Fe status. Following Fe enrichment, oceanic diatoms showed distinct differential expression of gene products involved in nitrogen assimilation, photosynthetic carbon fixation, and vitamin production compared to diatoms from low-Fe coastal sites, possibly driven by the chronic nature of Fe stress at the oceanic site. Genes of interest involved in Fe and N metabolism additionally exhibited divergent expression patterns between the two diatom taxa investigated, demonstrating that diverse diatoms may invoke alternative strategies when dealing with identical changes in their environment. We report here several mechanisms used distinctly by coastal or oceanic diatom communities as well as numerous taxa-specific strategies for coping with Fe stress and rearranging nutrient metabolism following Fe enrichment.</p

Image3.PDF

<p>Changes in iron (Fe) bioavailability influence diatom physiology and community composition, and thus have a profound impact on primary productivity and ecosystem dynamics. Iron limitation of diatom growth rates has been demonstrated in both oceanic and coastal waters of the Northeast Pacific Ocean and is predicted to become more pervasive in future oceans. However, it is unclear how the strategies utilized by phytoplankton to cope with low Fe bioavailability and resupply differ across these ocean provinces. We investigated the response of diatom communities to variable Fe conditions through incubation experiments performed in the Fe mosaic of the California Upwelling Zone and along a natural Fe gradient in the Northeast Pacific Ocean. Through coupling gene expression of two dominant diatom taxa (Pseudo-nitzschia and Thalassiosira) with biological rate process measurements, we provide an in-depth examination of the physiological and molecular responses associated with varying Fe status. Following Fe enrichment, oceanic diatoms showed distinct differential expression of gene products involved in nitrogen assimilation, photosynthetic carbon fixation, and vitamin production compared to diatoms from low-Fe coastal sites, possibly driven by the chronic nature of Fe stress at the oceanic site. Genes of interest involved in Fe and N metabolism additionally exhibited divergent expression patterns between the two diatom taxa investigated, demonstrating that diverse diatoms may invoke alternative strategies when dealing with identical changes in their environment. We report here several mechanisms used distinctly by coastal or oceanic diatom communities as well as numerous taxa-specific strategies for coping with Fe stress and rearranging nutrient metabolism following Fe enrichment.</p

Table3.XLSX

<p>Changes in iron (Fe) bioavailability influence diatom physiology and community composition, and thus have a profound impact on primary productivity and ecosystem dynamics. Iron limitation of diatom growth rates has been demonstrated in both oceanic and coastal waters of the Northeast Pacific Ocean and is predicted to become more pervasive in future oceans. However, it is unclear how the strategies utilized by phytoplankton to cope with low Fe bioavailability and resupply differ across these ocean provinces. We investigated the response of diatom communities to variable Fe conditions through incubation experiments performed in the Fe mosaic of the California Upwelling Zone and along a natural Fe gradient in the Northeast Pacific Ocean. Through coupling gene expression of two dominant diatom taxa (Pseudo-nitzschia and Thalassiosira) with biological rate process measurements, we provide an in-depth examination of the physiological and molecular responses associated with varying Fe status. Following Fe enrichment, oceanic diatoms showed distinct differential expression of gene products involved in nitrogen assimilation, photosynthetic carbon fixation, and vitamin production compared to diatoms from low-Fe coastal sites, possibly driven by the chronic nature of Fe stress at the oceanic site. Genes of interest involved in Fe and N metabolism additionally exhibited divergent expression patterns between the two diatom taxa investigated, demonstrating that diverse diatoms may invoke alternative strategies when dealing with identical changes in their environment. We report here several mechanisms used distinctly by coastal or oceanic diatom communities as well as numerous taxa-specific strategies for coping with Fe stress and rearranging nutrient metabolism following Fe enrichment.</p