Mind the Gap: Student Researchers Use Secondary Data to Explore Disparities in STEM Education

Large data sets offer opportunities for graduate students to become involved in meaningful research, but also comes with a unique set of challenges. This paper seeks to examine that relationship through utilizing the High School Longitudinal Study 2009 – representative of US ninth graders in 2009 (n = 21,444) – to examine a set of research questions about STEM interest and preparation amongst secondary students. Student researchers identified gaps in plans and outcomes with regards to race, gender, exceptionalities, and socioeconomic status. Findings indicated inequities that affect STEM outcomes. A significant interaction was found between students education expectations by gender on science self-efficacy [F(4,1264) = 2.797, p =.025]. This interaction was not observed for math self-efficacy. Females and underrepresented minorities were less likely to pursue computer science courses and computer science careers [Females: Χ2 (2, N = 20,594) = 111.500, p \u3c .0001; Minorities: Χ2 (2, N = 13,069) = 6.455, p = .040]. Students’ expectations for post-secondary education differed by IEP status and socioeconomic status [Χ2 (3, n =165,684) = 26.886, p = 0.001]. Finally, time spent in extracurricular activities impacted academic achievement and students in lower socioeconomic groups were less involved in extracurricular activities [Χ2 (4, n = 20,598) = 132.298, p \u3c .0001]

Upward revision of global fossil fuel methane emissions based on isotope database

Methane has the second-largest global radiative forcing impact of anthropogenic greenhouse gases after carbon dioxide, but our understanding of the global atmospheric methane budget is incomplete. The global fossil fuel industry (production and usage of natural gas, oil and coal) is thought to contribute 15 to 22 per cent of methane emissions to the total atmospheric methane budget. However, questions remain regarding methane emission trends as a result of fossil fuel industrial activity and the contribution to total methane emissions of sources from the fossil fuel industry and from natural geological seepage, which are often co-located. Here we re-evaluate the global methane budget and the contribution of the fossil fuel industry to methane emissions based on long-term global methane and methane carbon isotope records. We compile the largest isotopic methane source signature database so far, including fossil fuel, microbial and biomass-burning methane emission sources. We find that total fossil fuel methane emissions (fossil fuel industry plus natural geological seepage) are not increasing over time, but are 60 to 110 per cent greater than current estimates owing to large revisions in isotope source signatures. We show that this is consistent with the observed global latitudinal methane gradient. After accounting for natural geological methane seepage, we find that methane emissions from natural gas, oil and coal production and their usage are 20 to 60 per cent greater than inventories. Our findings imply a greater potential for the fossil fuel industry to mitigate anthropogenic climate forcing, but we also find that methane emissions from natural gas as a fraction of production have declined from approximately 8 per cent to approximately 2 per cent over the past three decades.Published88-916A. Geochimica per l'ambienteJCR Journa

Identification of genes associated with dissociation of cognitive performance and neuropathological burden: Multistep analysis of genetic, epigenetic, and transcriptional data

Introduction: The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation. Methods and findings: “Residual cognition” was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492) and the Rush Memory and Aging Project (n = 487). Given that our sample size was underpowered to detect genome-wide significance, we applied a multistep approach to identify genes influencing residual cognition, based on our prior observation that independent genetic and epigenetic risk factors can converge on the same locus. In the first step (n = 979), we performed a genome-wide association study with a predefined suggestive p < 10−5, and nine independent loci met this threshold in eight distinct chromosomal regions. Three of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral prefrontal cortex (DLPFC): UNC5C, ENC1, and TMEM106B. In the second step, in the subset of participants with DLPFC DNA methylation data (n = 648), we found that residual cognition was related to differential DNA methylation of UNC5C and ENC1 (false discovery rate < 0.05). In the third step, in the subset of participants with DLPFC RNA sequencing data (n = 469), brain transcription levels of UNC5C and ENC1 were evaluated for their association with residual cognition: RNA levels of both UNC5C (estimated effect = −0.40, 95% CI −0.69 to −0.10, p = 0.0089) and ENC1 (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 × 10−5) were associated with residual cognition. In secondary analyses, we explored the mechanism of these associations and found that ENC1 may be related to the previously documented effect of depression on cognitive decline, while UNC5C may alter the composition of presynaptic terminals. Of note, the TMEM106B allele identified in the first step as being associated with better residual cognition is in strong linkage disequilibrium with rs1990622A (r2 = 0.66), a previously identified protective allele for TDP-43 proteinopathy. Limitations include the small sample size for the genetic analysis, which was underpowered to detect genome-wide significance, the evaluation being limited to a single cortical region for epigenetic and transcriptomic data, and the use of categorical measures for certain non-amyloid-plaque, non-neurofibrillary-tangle neuropathologies. Conclusions: Through a multistep analysis of cognitive, neuropathological, genomic, epigenomic, and transcriptomic data, we identified ENC1 and UNC5C as genes with convergent genetic, epigenetic, and transcriptomic evidence supporting a potential role in the dissociation of cognition and neuropathology in an aging population, and we expanded our understanding of the TMEM106B haplotype that is protective against TDP-43 proteinopathy

Adverse events among Ontario home care clients associated with emergency room visit or hospitalization: a retrospective cohort study

Background: Home care (HC) is a critical component of the ongoing restructuring of healthcare in Canada. It impacts three dimensions of healthcare delivery: primary healthcare, chronic disease management, and aging at home strategies. The purpose of our study is to investigate a significant safety dimension of HC, the occurrence of adverse events and their related outcomes. The study reports on the incidence of HC adverse events, the magnitude of the events, the types of events that occur, and the consequences experienced by HC clients in the province of Ontario. Methods: A retrospective cohort design was used, utilizing comprehensive secondary databases available for Ontario HC clients from the years 2008 and 2009. The data were derived from the Canadian Home Care Reporting System, the Hospital Discharge Abstract Database, the National Ambulatory Care Reporting System, the Ontario Mental Health Reporting System, and the Continuing Care Reporting System. Descriptive analysis was used to identify the type and frequency of the adverse events recorded and the consequences of the events. Logistic regression analysis was used to examine the association between the events and their consequences. Results: The study found that the incident rate for adverse events for the HC clients included in the cohort was 13%. The most frequent adverse events identified in the databases were injurious falls, injuries from other than a fall, and medication-related incidents. With respect to outcomes, we determined that an injurious fall was associated with a significant increase in the odds of a client requiring long-term-care facility admission and of client death. We further determined that three types of events, delirium, sepsis, and medication-related incidents were associated directly with an increase in the odds of client death. Conclusions: Our study concludes that 13% of clients in homecare experience an adverse event annually. We also determined that an injurious fall was the most frequent of the adverse events and was associated with increased admission to long-term care or death. We recommend the use of tools that are presently available in Canada, such as the Resident Assessment Instrument and its Clinical Assessment Protocols, for assessing and mitigating the risk of an adverse event occurring.This work was supported by the Canadian Patient Safety Institute; Canadian Institutes of Health Research (CIHR) (Institutes of Health Services and Policy Research, Aging, Circulatory and Respiratory Health and Musculoskeletal Health and Arthritis); the Change Foundation; and the Canadian Health Services Research Foundation (grant number HC-10-05 Doran-Blais

Phenotypic and Genotypic Characterization and Treatment of a Cohort with Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome

Familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is a rare disorder caused by mutations in the genes encoding fibroblast growth factor-23 (FGF23), N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO. The result is functional deficiency of, or resistance to, intact FGF23 (iFGF23), causing hyperphosphatemia, increased renal tubular reabsorption of phosphorus (TRP), elevated or inappropriately normal 1,25-dihydroxyvitamin D3 (1,25D), ectopic calcifications and/or diaphyseal hyperostosis. Eight subjects with FTC/HHS were studied and treated. Clinical manifestations varied, even within families, ranging from asymptomatic to large, disabling calcifications. All subjects had hyperphosphatemia, increased TRP, and elevated or inappropriately normal 1,25D. C-terminal FGF23 was markedly elevated while iFGF23 was comparatively low, consistent with increased FGF23 cleavage. Radiographs ranged from diaphyseal hyperostosis to massive calcification. Two subjects with severe calcifications also had overwhelming systemic inflammation and elevated C-reactive protein (CRP). GALNT3 mutations were identified in 7 subjects; no causative mutation was found in the eighth. Biopsies from 4 subjects showed ectopic calcification and chronic inflammation, with areas of heterotopic ossification observed in 1 subject. Treatment with low phosphate diet, phosphate binders, and phosphaturia-inducing therapies was prescribed with variable response. One subject experienced complete resolution of a calcific mass after 13 months of medical treatment. In the 2 subjects with systemic inflammation, interleukin-1 (IL-1) antagonists significantly decreased CRP levels with resolution of calcinosis cutis and peri-lesional inflammation in one subject and improvement of overall well-being in both subjects. This cohort expands the phenotype and genotype of FTC/HHS and demonstrates the range of clinical manifestations despite similar biochemical profiles and genetic mutations. Overwhelming systemic inflammation has not been described previously in FTC/HHS; the response to IL-1 antagonists suggests that anti-inflammatory drugs may be useful adjuvants. In addition, this is the first description of heterotopic ossification reported in FTC/HHS, possibly mediated by the adjacent inflammation

Bioactive Endophytes Warrant Intensified Exploration and Conservation

A key argument in favor of conserving biodiversity is that as yet undiscovered biodiversity will yield products of great use to humans. However, the link between undiscovered biodiversity and useful products is largely conjectural. Here we provide direct evidence from bioassays of endophytes isolated from tropical plants and bioinformatic analyses that novel biology will indeed yield novel chemistry of potential value.We isolated and cultured 135 endophytic fungi and bacteria from plants collected in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the genetic novelty of cultured specimens. Ten endophytes were found to be as much as 15–30% different than any sequence in GenBank. Phylogenetic trees, using the most similar sequences in GenBank, were constructed for each endophyte to measure phylogenetic distance. Assays were also conducted on each cultured endophyte to record bioactivity, of which 65 were found to be bioactive.The novelty of our contribution is that we have combined bioinformatic analyses that document the diversity found in environmental samples with culturing and bioassays. These results highlight the hidden hyperdiversity of endophytic fungi and the urgent need to explore and conserve hidden microbial diversity. This study also showcases how undergraduate students can obtain data of great scientific significance

Trans-pQTL study identifies immune crosstalk between Parkinson and Alzheimer loci

Objective: Given evidence from genetic studies, we hypothesized that there may be a shared component to the role of myeloid function in Parkinson and Alzheimer disease (PD and AD) and assessed whether PD susceptibility variants influenced protein expression of well-established AD-associated myeloid genes in human monocytes. Methods: We repurposed data in which AD-related myeloid proteins CD33, TREM1, TREM2, TREML2, TYROBP, and PTK2B were measured by flow cytometry in monocytes from 176 participants of the PhenoGenetic Project (PGP) and Harvard Aging Brain Study. Linear regression was used to identify associations between 24 PD risk variants and protein expression. The 2 cohorts were meta-analyzed in a discovery analysis, and the 4 most strongly suggestive results were validated in an independent cohort of 50 PGP participants. Results: We discovered and validated an association between the PD risk allele rs12456492G in the RIT2 locus and increased CD33 expression (pjoint = 3.50 × 10−5) and found strongly suggestive evidence that rs11060180A in the CCDC62/HIP1R locus decreased PTK2B expression (pjoint = 1.12 × 10−4). Furthermore, in older individuals, increased CD33 expression on peripheral monocytes was associated with a greater burden of parkinsonism (p = 0.047), particularly bradykinesia (p = 6.64 × 10−3). Conclusions: We find that the rs12456492 PD risk variant affects expression of AD-associated protein CD33 in peripheral monocytes, which suggests that genetic factors for these 2 diseases may converge to influence overlapping innate immune-mediated mechanisms that contribute to neurodegeneration. Furthermore, the effect of the rs12456492G PD risk allele on increased CD33 suggests that the inhibition of certain myeloid functions may contribute to PD susceptibility, as is the case for AD