Statistics as Unbiased Estimators: Exploring the Teaching of Standard Deviation

This manuscript presents findings from a study about the knowledge for and planned teaching of standard deviation. We investigate how understanding variance as an unbiased (inferential) estimator – not just a descriptive statistic for the variation (spread) in data – is related to teachers’ instruction regarding standard deviation, particularly around the issue of division by n-1. In this regard, the study contributes to our understanding about how knowledge of mathematics beyond the current instructional level, what we refer to as nonlocal mathematics, becomes important for teaching. The findings indicate that acquired knowledge of nonlocal mathematics can play a role in altering teachers’ planned instructional approaches in terms of student activity and cognitive demand in their instruction

Secondary Mathematics Teachers’ Planned Approaches For Teaching Standard Deviation

Research-based guidelines for learning variation exist (e.g., Franklin et al., 2007; Garfield, delMas, & Chance, 2007), but little is known about how teachers plan to teach standard deviation, or how these plans align with recent recommendations. In this article, we survey lesson plans designed by inservice and preservice secondary mathematical teachers. We report on the accuracy, technology usage, and visual representations in the lesson plans. We consider how many elements are used, the level of conceptual development, and the mathematical nature. Findings support differences between preservice and master’s level students in education, as well as a tendency by in-service teachers to teach in alignment with prior learning experiences, despite professional development. Implications for teacher education and curricular development are offered

Quantitative neuroanatomy for connectomics in Drosophila

Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity.Publisher PDFPeer reviewe

Fast Healthcare Interoperability Resources (FHIR) as a Meta Model to Integrate Common Data Models: Development of a Tool and Quantitative Validation Study

BACKGROUND: In a multisite clinical research collaboration, institutions may or may not use the same common data model (CDM) to store clinical data. To overcome this challenge, we proposed to use Health Level 7's Fast Healthcare Interoperability Resources (FHIR) as a meta-CDM-a single standard to represent clinical data. OBJECTIVE: In this study, we aimed to create an open-source application termed the Clinical Asset Mapping Program for FHIR (CAMP FHIR) to efficiently transform clinical data to FHIR for supporting source-agnostic CDM-to-FHIR mapping. METHODS: Mapping with CAMP FHIR involves (1) mapping each source variable to its corresponding FHIR element and (2) mapping each item in the source data's value sets to the corresponding FHIR value set item for variables with strict value sets. To date, CAMP FHIR has been used to transform 108 variables from the Informatics for Integrating Biology & the Bedside (i2b2) and Patient-Centered Outcomes Research Network data models to fields across 7 FHIR resources. It is designed to allow input from any source data model and will support additional FHIR resources in the future. RESULTS: We have used CAMP FHIR to transform data on approximately 23,000 patients with asthma from our institution's i2b2 database. Data quality and integrity were validated against the origin point of the data, our enterprise clinical data warehouse. CONCLUSIONS: We believe that CAMP FHIR can serve as an alternative to implementing new CDMs on a project-by-project basis. Moreover, the use of FHIR as a CDM could support rare data sharing opportunities, such as collaborations between academic medical centers and community hospitals. We anticipate adoption and use of CAMP FHIR to foster sharing of clinical data across institutions for downstream applications in translational research

Measurement of the Branching Fraction for B->eta' K and Search for B->eta'pi+

We report measurements for two-body charmless B decays with an eta' meson in the final state. Using 11.1X10^6 BBbar pairs collected with the Belle detector, we find BF(B^+ ->eta'K^+)=(79^+12_-11 +-9)x10^-6 and BF(B^0 -> eta'K^0)=(55^+19_-16 +-8)x10^-6, where the first and second errors are statistical and systematic, respectively. No signal is observed in the mode B^+ -> eta' pi^+, and we set a 90% confidence level upper limit of BF(B^+-> eta'pi^+) eta'K^+- decays is investigated and a limit at 90% confidence level of -0.20<Acp<0.32 is obtained.Comment: Submitted to Physics Letters

Cowries in the archaeology of West Africa: the present picture

Despite the perceived importance of cowrie shells as indicators of long-distance connections in the West African past, their distribution and consumption patterns in archaeological contexts remain surprisingly underexplored, a gap that is only partly explicable by the sparse distribution of archaeological sites within the sub-continent. General writings on the timeline of importation of cowries into West Africa often fail to take into account the latest archaeological evidence and rely instead on accounts drawn from historical or ethnographic documents. This paper is based on a first-hand assessment of over 4500 shells from 78 sites across West Africa, examining chronology, shell species and processes of modification to assess what distribution patterns can tell us about the history of importation and usage of cowries. These first-hand analyses are paralleled by a consideration of published materials. We re-examine the default assumption that two distinct routes of entry existed — one overland from North Africa before the fifteenth century, another coming into use from the time sea links were established with the East African coast and becoming predominant by the middle of the nineteenth century. We focus on the eastern part of West Africa, where the importance of imported cowries to local communities in relatively recent periods is well known and from where we have a good archaeological sample. The conclusion is that on suitably large assemblages shell size can be an indication of provenance and that, while the present archaeological picture seems largely to confirm historical sources, much of this may be due to the discrepancy in archaeological data available from the Sahara/Sahel zone compared to the more forested regions of the sub-continent. Future archaeological work will clarify this matter

Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner

Study question: Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? Summary answer: T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. What is known already: Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 mayalso have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. Study design, size, duration: This laboratory-based study used human decidua from first (8–11 weeks; n ¼ 18) and second (12–16 weeks; n ¼ 12) trimester surgical terminations of apparently uncomplicated pregnancies. Participants/materials, setting, methods: Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD102) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel was evaluated. Main results and the role of chance: Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRa1, TRb1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P , 0.05) and increased angiopoietin-2 secretion by stromal depleted cells (P , 0.05) but in the second trimester total decidual cells showed only increased angiogenin secretion (P , 0.05). In the first trimester, T3 reduced IL-10 secretion by total decidual cells (P , 0.05), and reduced granulocyte macrophage colony stimulating factor (P , 0.01), IL-8 (P , 0.05), IL-10 (P , 0.01), IL-1b (P , 0.05) and monocyte chemotactic protein -1 (P , 0.001) secretion by macrophages, but increased tumour necrosis factor-a secretion by stromal-depleted cells (P , 0.05) and increased IL-6 by uNK cells (P , 0.05). In contrast, in the second trimester T3 increased IL-10 secretion by total decidual cells (P , 0.01) but did not affect cytokine secretion byuNKcells and macrophages. Conditioned media from first trimester T3-treated total decidual cells and macrophages did not alter EVT invasion compared with untreated controls. Thus, treatment of decidual cells with T3 resulted in changes in both angiogenic growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro. Limitations, reasons for caution: Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo. Wider implications of the findings: Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental development through the regulation of the secretion of critical cytokines and angiogenic growth factors by human decidual cells. Our data suggest that there is an ontogenically determined regulatory ‘switch’ in T3 responsiveness between the first and second trimesters, and support the notion that the timely and early correction of maternal thyroid dysfunction is critical in influencing pregnancy outcomes

Searching for continuous Gravitational Waves in the second data release of the International Pulsar Timing Array

The International Pulsar Timing Array 2nd data release is the combination of datasets from worldwide collaborations. In this study, we search for continuous waves: gravitational wave signals produced by individual supermassive black hole binaries in the local universe. We consider binaries on circular orbits and neglect the evolution of orbital frequency over the observational span. We find no evidence for such signals and set sky averaged 95% upper limits on their amplitude h 95 . The most sensitive frequency is 10nHz with h 95 = 9.1 10-15 . We achieved the best upper limit to date at low and high frequencies of the PTA band thanks to improved effective cadence of observations. In our analysis, we have taken into account the recently discovered common red noise process, which has an impact at low frequencies. We also find that the peculiar noise features present in some pulsars data must be taken into account to reduce the false alarm. We show that using custom noise models is essential in searching for continuous gravitational wave signals and setting the upper limit

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival