Statistical Analysis When the Data is an Image: Eliciting Student Thinking About Sampling and Variability

Within statistics education, there is a growing interest in understanding students\u27 application of understanding about variability and sampling given the relative lack of research in either area (Shaughnessy, 2007). The task examined in this paper elicited students\u27 knowledge of these concepts within a small-group problem solving task completed by teams of first-year engineering students. In the Nanoroughness task, teams of students designed a procedure for quantifying the roughness of a material surface using digital images generated by atomic force microscopy. The procedure required students to apply statistical methods in order to aggregate the data. The focus of this article is the subsequent analysis of the responses to the task and the questions raised by that analysis. The Nanoroughness task is unique but critical as a statistical modeling task for two reasons. First, the students needed to use statistical measures to develop a measure that would describe a qualitative characteristic (roughness) without any prompting as to what statistical procedures were relevant. There are different ways to conceptualize roughness of a surface. Sandpaper’s roughness depends on the grain size of the sand. A road may be rough if it has randomly occurring large holes but smoother if the bumps are evenly distributed. The challenge in developing quantitative measures to define qualitative characteristics is that different quantitative analyses emphasize different variables and the students needed to both analyze and apply statistical procedures relevant to the context. For instance, determining which member of a set is the most rough or the least rough will depend on what measurements were selected, and how those measures were analyzed. The second unique characteristic of the task is that the students also needed to define a sampling procedure for an image that would facilitate quantifying the variability in the surface portrayed in the digital image. Usually when students need to take measurements of a population, the population is a discrete set of objects. In this case, the data set was a continuous surface. From the data set, the students need to determine the relevant population (e.g., every point on the surface, every peak on the surface, peaks and valleys). Such continuous populations are not unique within engineering and the sciences and occur in a variety of contexts where characteristics need to be measured and operationally defined. The task was implemented in a first-year engineering course that served as an introduction to basic tools of engineering with an emphasis on MatLab® and Excel® as technological tools. The Nanoroughness task was used in the course to introduce students to the real work of engineers who must not only calculate statistics but also analyze and interpret the results. Our research asked a two-part question. First, what is the quality of student responses to the Nanoroughness task? To answer this we looked at the viability of the model they had created and how well they had explained their procedure for comparing the roughness of images. Second, what statistical models were elicited by the task? We specifically looked at the sampling methods students used and then how the students analyzed the data set they had created. In this paper, we describe the quantitative and qualitative analyses we completed of a sample of student responses

Bacterial diversity of autotrophic enriched cultures from remote, glacial Antarctic, Alpine and Andean aerosol, snow and soil samples

International audienceFour different communities and one culture of autotrophic microbial assemblages were obtained by incubation of samples collected from high elevation snow in the Alps (Mt. Blanc area) and the Andes (Nevado Illimani summit, Bolivia), from Antarctic aerosol (French station Dumont d'Urville) and a maritime Antarctic soil (King George Island, South Shetlands, Uruguay Station Artigas), in a minimal mineral (oligotrophic) media. Molecular analysis of more than 200 16S rRNA gene sequences showed that all cultured cells belong to the Bacteria domain. Phylogenetic comparison with the currently available rDNA database allowed sequences belonging to Proteobacteria (Alpha-, Betaand Gamma-proteobacteria) , Actinobacteria and Bacteroidetes phyla to be identified. The Andes snow culture was the richest in bacterial diversity (eight microorganisms identified) and the marine Antarctic soil the poorest (only one). Snow samples from Col du Midi (Alps) and the Andes shared the highest number of identified microorganisms (Agrobacterium, Limnobacter, Aquiflexus and two uncultured Alphaproteobacteria clones). These two sampling sites also shared four sequences with the Antarctic aerosol sample (Limnobacter, Pseudonocardia and an uncultured Alphaproteobacteria clone). The only microorganism identified in the Antarctica soil (Brevundimonas sp.) was also detected in the Antarctic aerosol. Most of the identified microorganisms had been detected previously in cold environments, marine sediments soils and rocks. Air current dispersal is the best model to explain the presence of very specific microorganisms, like those identified in this work, in environments very distant and very different from each other

Linking Antarctic glaciochemical records to past climate conditions (scientific paper)

Deep Antarctic ice cores document the former states of the climatic system, the atmosphere, and the marine and terrestrial biospheres. However, questions do remain in the interpretation and the reliability of ice core chemical profiles in terms of atmospheric information. Data from the Dome C, Vostok, Dome F, and EPICA deep ice cores are used and compared in the discussions. First of all, the transfer functions of various gaseous and particulate compounds are not entirely understood and in the case of acid gases, strong post-deposition effects are observed at central Antarctic sites. It is emphasised that marine primary and secondary aerosol species may strongly interact during their long-range transport. Continental aerosol is important for the Antarctic impurity budget only in glacial environmental conditions. Its composition, as derived from Antarctic ice core glaciochemistry is discussed. As for the case of marine aerosol, the reaction of primary and gas-derived aerosol has to be considered. Finally, the possible impact of continental dust on marine biogenic activity shortly is discussed in the light of glaciochemical results

Coordination by Cdc42 of actin, contractility, and adhesion for melanoblast movement in mouse skin

YesThe individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.Cancer Research UK (to L.M.M. [A17196], R.H.I. [A19257], and S.W.G.T.) and NIH grants P01-GM103723 and P41-EB002025 (to K.M.H.). N.R.P. is supported by a Pancreatic Cancer Research Fund grant (to L.M.M.). Funding to Prof. Rottner by the Deutsche Forschungsgemeinschaft (grant RO2414/3-2)

GLI2-Mediated Melanoma Invasion and Metastasis

Background The transforming growth factor-β (TGF-β) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-β signaling. Methods We used real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting to determine GLI2 expression in human melanoma cell lines and subsequently classified them as GLI2high or as GLI2low according to their relative GLI2 mRNA and protein expression levels. GLI2 expression was reduced in a GLI2high cell line with lentiviral expression of short hairpin RNA targeting GLI2. We assessed the role of GLI2 in melanoma cell invasiveness in Matrigel assays. We measured secretion of matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography and expression of E-cadherin by western blotting and RT-PCR. The role of GLI2 in development of bone metastases was determined following intracardiac injection of melanoma cells in immunocompromised mice (n = 5-13). Human melanoma samples (n = 79) at various stages of disease progression were analyzed for GLI2 and E-cadherin expression by immunohistochemistry, in situ hybridization, or RT-PCR. All statistical tests were two-sided. Results Among melanoma cell lines, increased GLI2 expression was associated with loss of E-cadherin expression and with increased capacity to invade Matrigel and to form bone metastases in mice (mean osteolytic tumor area: GLI2high vs GLI2low, 2.81 vs 0.93 mm2, difference = 1.88 mm2, 95% confidence interval [CI] = 1.16 to 2.60, P < .001). Reduction of GLI2 expression in melanoma cells that had expressed high levels of GLI2 substantially inhibited both basal and TGF-β-induced cell migration, invasion (mean number of Matrigel invading cells: shGLI2 vs shCtrl (control), 52.6 vs 100, difference = 47.4, 95% CI = 37.0 to 57.8, P = .024; for shGLI2 + TGF-β vs shCtrl + TGF-β, 31.0 vs 161.9, difference = −130.9, 95% CI = −96.2 to −165.5, P = .002), and MMP secretion in vitro and the development of experimental bone metastases in mice. Within human melanoma lesions, GLI2 expression was heterogeneous, associated with tumor regions in which E-cadherin was lost and increased in the most aggressive tumors. Conclusion GLI2 was directly involved in driving melanoma invasion and metastasis in this preclinical stud

The Global Longitudinal Study of Osteoporosis in Women (GLOW): rationale and study design

SUMMARY: The Global Longitudinal study of Osteoporosis in Women (GLOW) is a prospective cohort study involving 723 physicians and 60,393 women subjects \u3eor=55 years. The data will provide insights into the management of fracture risk in older women over 5 years, patient experience with prevention and treatment, and distribution of risk among older women on an international basis. INTRODUCTION: Data from cohort studies describing the distribution of osteoporosis-related fractures and risk factors are not directly comparable and do not compare regional differences in patterns of patient management and fracture outcomes. METHODS: The GLOW is a prospective, multinational, observational cohort study. Practices typical of each region were identified through primary care networks organized for administrative, research, or educational purposes. Noninstitutionalized patients visiting each practice within the previous 2 years were eligible. Self-administered questionnaires were mailed, with 2:1 oversampling of women \u3eor=65 years. Follow-up questionnaires will be sent at 12-month intervals for 5 years. RESULTS: A total of 723 physicians at 17 sites in ten countries agreed to participate. Baseline surveys were mailed (October 2006 to February 2008) to 140,416 subjects. After the exclusion of 3,265 women who were ineligible or had died, 60,393 agreed to participate. CONCLUSIONS: GLOW will provide contemporary information on patterns of management of fracture risk in older women over a 5-year period. The collection of data in a similar manner in ten countries will permit comparisons of patient experience with prevention and treatment and provide insights into the distribution of risk among older women on an international basis

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p &lt; 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM &gt; 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM &gt; 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

YY1 Regulates Melanocyte Development and Function by Cooperating with MITF

Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP–seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)—a general mechanism which may confer tissue-specific gene expression in multiple lineages