A Developmental Approach to Machine Learning?

Visual learning depends on both the algorithms and the training material. This essay considers the natural statistics of infant- and toddler-egocentric vision. These natural training sets for human visual object recognition are very different from the training data fed into machine vision systems. Rather than equal experiences with all kinds of things, toddlers experience extremely skewed distributions with many repeated occurrences of a very few things. And though highly variable when considered as a whole, individual views of things are experienced in a specific order – with slow, smooth visual changes moment-to-moment, and developmentally ordered transitions in scene content. We propose that the skewed, ordered, biased visual experiences of infants and toddlers are the training data that allow human learners to develop a way to recognize everything, both the pervasively present entities and the rarely encountered ones. The joint consideration of real-world statistics for learning by researchers of human and machine learning seems likely to bring advances in both disciplines

Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers

Background: Patient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of in situ microenvironment affects the clinically-predictive value of this model. We implemented a GSC monolayer system to investigate in situ-in vitro molecular correspondence and the relationship between in vitro and patient response to temozolomide (TMZ). Methods: DNA/RNA-sequencing was performed on 56 glioblastoma tissues and 19 derived GSC cultures. Sensitivity to TMZ was screened across 66 GSC cultures. Viability readouts were related to clinical parameters of corresponding patients and whole-transcriptome data. Results: Tumour DNA and RNA sequences revealed strong similarity to corresponding GSCs despite loss of neuronal and immune interactions. In vitro TMZ screening yielded three response categories which significantly correlated with patient survival, therewith providing more specific prediction than the binary MGMT marker. Transcriptome analysis identified 121 genes related to TMZ sensitivity of which 21were validated in external datasets. Conclusion:GSCs retain patient-unique hallmark gene expressions despite loss of their natural environment. Drug screening using GSCs predicted patient response to TMZ more specifically than MGMT status, while transcriptome analysis identified potential biomarkers for this response. GSC drug screening therefore provides a tool to improve drug development and precision medicine for glioblastoma.</p

Testing the lognormality of the galaxy and weak lensing convergence distributions from Dark Energy Survey maps

It is well known that the probability distribution function (PDF) of galaxy density contrast is approximately lognormal; whether the PDF of mass fluctuations derived from weak lensing convergence (kappa_WL) is lognormal is less well established. We derive PDFs of the galaxy and projected matter density distributions via the Counts in Cells (CiC) method. We use maps of galaxies and weak lensing convergence produced from the Dark Energy Survey (DES) Science Verification data over 139 deg^2. We test whether the underlying density contrast is well described by a lognormal distribution for the galaxies, the convergence and their joint PDF. We confirm that the galaxy density contrast distribution is well modeled by a lognormal PDF convolved with Poisson noise at angular scales from 10-40 arcmin (corresponding to physical scales of 3-10 Mpc). We note that as kappa_WL is a weighted sum of the mass fluctuations along the line of sight, its PDF is expected to be only approximately lognormal. We find that the kappa_WL distribution is well modeled by a lognormal PDF convolved with Gaussian shape noise at scales between 10 and 20 arcmin, with a best-fit chi^2/DOF of 1.11 compared to 1.84 for a Gaussian model, corresponding to p-values 0.35 and 0.07 respectively, at a scale of 10 arcmin. Above 20 arcmin a simple Gaussian model is sufficient. The joint PDF is also reasonably fitted by a bivariate lognormal. As a consistency check we compare the variances derived from the lognormal modelling with those directly measured via CiC. Our methods are validated against maps from the MICE Grand Challenge N-body simulation

Weak lensing magnification in the dark energy survey science verification data

In this paper, the effect of weak lensing magnification on galaxy number counts is studied by cross-correlating the positions of two galaxy samples, separated by redshift, using the Dark Energy Survey Science Verification data set. This analysis is carried out for galaxies that are selected only by its photometric redshift. An extensive analysis of the systematic effects, using new methods based on simulations is performed, including a Monte Carlo sampling of the selection function of the survey

The Dark Energy Survey: more than dark energy – an overview

This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be _+cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)

The Dark Energy Survey : more than dark energy – an overview

This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)

Preclinical interrogation of novel immunotherapy treatment strategies in glioblastoma (GBM) using a novel clinically relevant disease model

Reliable and clinically faithful pre-clinical glioblastoma (GBM) models are essential for the screening of new therapies and to understand treatment resistance mechanisms. Historically models have failed to predict response in the clinical setting. As a result, many clinical trials fail to meet their primary endpoint, despite promising preclinical data. Moreover, current GBM models seldom incorporate surgical resection and/or standard of care chemotherapy treatment, commonly employing young animals whose immune contexture differs from older patients. Here, we have established an orthotopic GBM model, which employs the syngeneic, mesenchymal-NFpp10a-cell line, in both young and aged mice. We have characterised the model in response to standard of care (SOC) resection and temozolomide (TMZ) treatment. We have further studied response to experimental treatments with anti-PD1 (adjuvant and neoadjuvant). NFpp10a-Luc2 expressing cells were orthotopically implanted into C57BL/6-mice (male and female, aged [>18months] and young [6-8weeks]) and weekly bioluminescence imaging (BLI) performed to monitor tumour growth. Several therapeutic interventions were subsequently assessed to study anti-tumour efficacy and overall survival (OS). The treatment panel included (1) surgical resection of tumour (Sweeney et al., 2014), (2) TMZ therapy (oral gavage; 50 mg/kg; 5 consecutive days in each 28-day cycle) (3) Anti-PD1 therapy (intraperitoneal; 250 ug; day 10, 12 & 14 post-tumour implantation), (4) Neoadjuvant (NA) anti-PD1 therapy (intraperitoneal; 100 ug; Day 5 and 3 pre-tumour resection), Response to therapy was assessed via longitudinal BLI. Tissue collected postmortem has undergone bulk RNA sequencing. Transcriptomic data underwent microenvironment cell population (MCP) analyses to determine the absolute abundance of eight immune and two stromal cell populations within tumours and to study how these populations changed following treatment. Gene set enrichment analysis (GSEA) was further employed to determine gene expression pathway changes We demonstrated survival advantage in aged mice undergoing surgical resection (Resection:33.5 days vs Non-Resection: 18 days; p= 0.0166) and observed age to be a significant prognostic factor (Young:62 days vs Aged: 22 days; p=0.0002). Subsequently, we observed that TMZ and anti-PD1 monotherapy had no impact on NFpp10-Luc2 growth (TMZ-overall: p=0.9001, anti-PD1-overall: p=0.7933) or survival (TMZ- overall: p=0.3035, anti-PD1-overall: p=0.6328). Neoadjuvant anti-PD1 treated mice 21 demonstrated no significant survival advantage compared to IgG control (33 days vs 35 days; p=0.9429) or BLI signal (p=0.1703). NFpp10a forms immune-cold TME relative to commonly employed models. Neoadjuvant anti-PD1 induced influx of CD8+ T cells, B cells and monocytes into the TME and was associated with upregulation of CXCR3 in gene set enrichment analysis (p=0.0045). Overall, we have, for the first time, established and characterised response of the NFpp10a-C57BL/6 model to surgical resection, TMZ and anti-PD1 therapy in young and aged mice. We have shown that the model is markedly insensitive to intervention with chemotherapy and immune checkpoint therapy, mirroring what is seen clinically in patients. The model may therefore be employed in future pre-clinical studies to guide clinical trials in the setting of mesenchymal GBM. </p

A 2MASS study of candidate precursors to UCHII regions

There has been two major efforts in the past 7 years to study UCHII regions (Molinari et al. 1996; Sridharan et al., 2002). They compiled a list of 217 best candidates of the precursors to UCHII regions. We conducted a near IR study into these sources using the 2MASS all sky survey. A method of Nyquist bining stellar counts around these sources revealed the presence of embedded clusters in at least 63 (30%) of the sample. More than 50 of these were previously unknown groupings, 29 are classified as large clusters, 18 as small and the rest as stellar groups. This technique of detection provided stellar density contour maps which allowed us to discuss the morphology of the groupings. We estimated that the ratio of Hierarchical type to central condensed type cluster (H/C = 0.9 \approx 1) which possibly implies both a basic unity of gravity and turbulence but also maybe the decay of the turbulence with time. The positions of the candidate (pre) UCHII regions show a striking preference for the very centre of the clusters. We statistically calculate the number of cluster members detectable by the 2MASS telescope, and we extend this estimate and the mass to almost the deuterium burning limit with the use of an universal IMF from Muench et al. (2002). We observe a correlation between the relative age of the (pre) UCHII regions and the number of members in the clusters. With the use of cc-diagrams, we obtained the average dust extinction and we discussed the colours of massive protostars. The mass of the dust cloud was available for 15 clusters from Beuther et al. (2002) and so, we estimated the local star formation efficiency

Current recommendations for surveillance and surgery of intraductal papillary mucinous neoplasms may overlook some patients with cancer.

BackgroundThe 2012 Sendai Criteria recommend that patients with 3 cm or larger branch duct intraductal papillary mucinous neoplasms (BD-IPMN) without any additional "worrisome features" or "high-risk stigmata" may undergo close observation. Furthermore, endoscopic ultrasound (EUS) is not recommended for BD-IPMN &lt;2 cm. These changes have generated concern among physicians treating patients with pancreatic diseases. The purposes of this study were to (i) apply the new Sendai guidelines to our institution's surgically resected BD-IPMN and (ii) reevaluate cyst size cutoffs in identifying patients with lesions harboring high-grade dysplasia or invasive cancer.MethodsWe retrospectively reviewed 150 patients at a university medical center with preoperatively diagnosed and pathologically confirmed IPMNs. Sixty-six patients had BD-IPMN. Pathologic grade was dichotomized into low-grade (low or intermediate grade dysplasia) or high-grade/invasive (high-grade dysplasia or invasive cancers). Fisher's exact test, chi-square test, student's t test, linear regression, and receiver operating characteristic (ROC) analyses were performed.ResultsThe median BD-IPMN size on imaging was 2.4 cm (interquartile range 1.5-3.0). Fifty-one (77 %) low-grade and 15 (23 %) high-grade/invasive BD-IPMN were identified. ROC analysis demonstrated that cyst size on preoperative imaging is a reasonable predictor of grade with an area under the curve of 0.691. Two-thirds of high-grade/invasive BD-IPMN were &lt;3 cm (n = 10). Compared to a cutoff of 3, 2 cm was associated with higher sensitivity (73.3 vs. 33.3 %) and negative predictive value (83.3 vs. 80 %, NPV) for high-grade/invasive BD-IPMN. Mural nodules on endoscopic ultrasound (EUS) or atypical cells on endoscopic ultrasound-fine needle aspiration (EUS-FNA) were identified in all cysts &lt;2 and only 50 % of those &lt;3 cm. Forty percent of cysts &gt;3 cm were removed based on size alone.Discussion/conclusionsOur results suggest that "larger" size on noninvasive imaging can indicate high-grade/invasive cysts, and EUS-FNA may help identify "smaller" cysts with high-grade/invasive pathology