Kepler Archive Manual

A description of Kepler, its design, performance and operational constraints may be found in the Kepler Instrument Handbook (KIH, Van Cleve Caldwell 2016). A description of Kepler calibration and data processing is described in the Kepler Data Processing Handbook (KDPH, Jenkins et al. 2016; Fanelli et al. 2011). Science users should also consult the special ApJ Letters devoted to early Kepler results and mission design (April 2010, ApJL, Vol. 713 L79-L207). Additional technical details regarding the data processing and data qualities can be found in the Kepler Data Characteristics Handbook (KDCH, Christiansen et al. 2013) and the Data Release Notes (DRN). This archive manual specifically documents the file formats, as they exist for the last data release of Kepler, Data Release 25(KSCI-19065-002). The earlier versions of the archive manual and data release notes act as documentation for the earlier versions of the data files

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Author version made available in accordance with publisher policy.Abstract Background The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett’s esophagus. Methods Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett’s esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett’s esophagus (Mann-Whitney U test, P<0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett’s esophagus (linear regression, P0.7, P<0.05). A multi-biomarker panel (RNU6-1/miR- 16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR- 30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC=0.99, 95 % CI 0.96–1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett’s esophagus. Conclusions This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma

‘Re-reading Raphael Samuel: Politics, Personality and Performance’

For British historian Raphael Samuel, history and politics were inextricable. Best known as the founder of the history workshop movement, the controversial historian took his stance on the democratisation of history-making, becoming an outspoken advocate for public history. Despite making a significant contribution to contemporary historiography, he remains a neglected, even disparaged, figure. This paper contends that the most significant aspect of Samuel’s historical work was not one or other theory of history or argument about the past but his entire way of being an historian. Samuel embodied as much as expressed his ideas, consciously using his personality as a powerful political tool. It is further argued that conventional approaches to intellectual history, focusing on textual outputs, do not fully recognise the significance of performative modes of thinking. Theoretical approaches to performance as identity offer important insight here but can be too schematic in their view of applied and enacted thought. A biographical approach, by contrast, provides the intimate perspective necessary to fully appreciate the fluidity and complexity of such a personality. The paper first situates Samuel in the context of his earlier life, focusing on how and why he created such a public persona and how he adapted it in response to changing circumstances. It then considers the implications and effectiveness of this persona by assessing how it was perceived and narrated by others, acknowledging, in the process, why different groups engaged with and interpreted it differently

Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie

Delayed deglaciation or extreme Arctic conditions 21-16 cal. kyr at southeastern Laurentide Ice Sheet margin?

The conventionally accepted ages of the Last Glacial Maximum (LGM) retreat of the southeastern Laurentide Ice Sheet (LIS) are 26–21 cal. kyr (derived from bulk-sediment radiocarbon ages) and 28–23 cal. kyr (varve estimates). Utilizing accelerator mass spectrometry (AMS) 14C dating of earliest macrofossils in 13 lake/bog inorganic clays, we find that vegetation first appeared on the landscape at 16–15 cal. kyr, suggesting ice had not retreated until that time. The gap between previous age estimates and ours is significant and has large implications for our understanding of ocean-atmosphere linkages. Older ages imply extreme Arctic conditions for 9–5 cal kyr; a landscape with no ice, yet no deposition in lakes. Our new AMS chronology of LIS retreat is consistent with marine evidence of deglaciation from the N. Atlantic, showing significant freshwater input and sea level rise only after 19 cal kyr with a cold meltwater lid, perhaps delaying ice melt

Functional organisation for verb generation in children with developmental language disorder

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10–15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance.</p

Full field electroretinogram in autism spectrum disorder

Purpose To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. Methods Dark adapted (DA) ERGs were acquired to a range of flash strengths, (-4.0 to 2.3 log phot cd.s.m-2), including and extending the ISCEV standard, from two subject groups: (ASD) N=11 and (Control) N=15 for DA and N=14 for light adapted (LA) ERGs who were matched for mean age and range. Naka-Rushton curves were fitted to DA b-wave amplitude growth over the first limb (-4.0 to -1.0 log phot cd.s.m-2). The derived parameters (Vmax, Km and n) were compared between groups. Scotopic 15 Hz flicker ERGs (14.93Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td.s to assess the slow and fast rod pathways respectively. LA ERGs were acquired to a range of flash strengths, (-0.5 to 1.0 log phot cd.s.m-2). Photopic 30 Hz, flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120 ms ON- OFF stimuli were also recorded. Results For some individuals the DA b-wave amplitudes fell below the control 5th centile of the controls with up to four ASD participants (36%) at the 1.5 log phot cd.s.m-2 flash strength and two (18%) ASD participants at the lower -2 log phot cd.s.m-2 flash strength. However, across the thirteen flash strengths there were no significant group differences for b-wave amplitude’s growth (repeated measures ANOVA p=0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p>0.09). No group differences were observed in the 15Hz scotopic flicker phase or amplitude (p>0.1), DA ERG a- wave amplitude or time to peak (p>26). The DA b-wave time to peak at 0.5 log phot cd.s.m-2 were longer in the ASD group (corrected p=0.04). The single ISCEV LA 0.5 log phot cd.s.m-2 (p0.08) to the single flash stimuli although there was a significant interaction between group and flash strength for the b-wave amplitude (corrected p=0.006). The prolonged 120 ms ON-responses were smaller in the ASD group (corrected p=0.003), but the OFF response amplitude (p>0.6) and ON and OFF times to peaks (p>0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants, however no other differences were apparent in the OPs or 30Hz flicker waveforms. Conclusion Some ASD individuals show subnormal DA ERG b-wave amplitudes. Under LA conditions the b-wave is reduced across the ASD group along with the ON response of the ERG. These exploratory findings, suggest there is altered cone-ON bipolar signalling in ASD

Motion and pattern cortical potentials in adults with high-functioning autism spectrum disorder

Purpose: Autism spectrum disorder (ASD) is a condition in which visual perception to both static and moving stimuli is altered. The aim of this study was to investigate the early cortical responses of subjects with ASD to simple patterns and moving radial rings using visual evoked potentials (VEPs). Methods: Male ASD participants (n = 9) and typically developing (TD) individuals (n = 7) were matched for full, performance and verbal IQ (p > 0.263). VEPs were recorded to the pattern reversing checks of 50′ side length presented with Michelson contrasts of 98 and 10 % and to the onset of motion—either expansion or contraction of low-contrast concentric rings (33.3 % duty cycle at 10 % contrast). Results: There were no significant differences between groups in the VEPs elicited by pattern reversal checkerboards of high (98 %) or low (10 %) contrast. The ASD group had a significantly larger N160 peak (1.85 x) amplitude to motion onset VEPs elicited by the expansion of radial rings (p = 0.001). No differences were evident in contraction VEP peak amplitudes nor in the latencies of the motion onset N160 peaks. There was no evidence of a response that could be associated with adaptation to the motion stimulus in the interstimulus interval following an expansion or contraction phase of the rings. Conclusion: These data support a difference in processing of motion onset stimuli in this adult high-functioning ASD group compared to the TD group

ISCEV standard pattern reversal VEP development: paediatric reference limits from 649 healthy subjects

Purpose: To establish the extent of agreement for ISCEV standard reference pattern reversal VEPs (prVEPs) acquired at three European centres, to determine any effect of sex, and to establish reference intervals from birth to adolescence. Methods: PrVEPs were recorded from healthy reference infants and children, aged 2 weeks to 16 years, from three centres using closely matched but non-identical protocols. Amplitudes and peak times were modelled with orthogonal quadratic and sigmoidal curves, respectively, and two-sided limits, 2.5th and 97.5th centiles, estimated using nonlinear quantile Bayesian regression. Data were compared by centre and by sex using median quantile confidence intervals. The ‘critical age’, i.e. age at which P100 peak time ceased to shorten, was calculated. Results: Data from the three centres were adequately comparable. Sex differences were not clinically meaningful. The pooled data showed rapid drops in P100 peak time which stabilised by 27 and by 34 weeks for large and small check widths, respectively. Post-critical-age reference limits were 87–115 ms and 96–131 ms for large and small check widths, respectively. Amplitudes varied markedly and reference limits for all ages were 5–57 μV and 3.5–56 μV for large and small check widths, respectively. Conclusions: PrVEP reference data could be combined despite some methodology differences within the tolerances of the ISCEV VEP Standard, supporting the clinical benefit of ISCEV Standards. Comparison with historical data is hampered by lack of minimum reporting guidelines. The reference data presented here could be validated or transformed for use elsewhere

Generalized models for quantifying laterality using functional transcranial Doppler ultrasound

We consider how analysis of brain lateralization using functional transcranial Doppler ultrasound (fTCD) data can be brought in line with modern statistical methods typically used in functional magnetic resonance imaging (fMRI). Conventionally, a laterality index is computed in fTCD from the difference between the averages of each hemisphere's signal within a period of interest (POI) over a series of trials. We demonstrate use of generalized linear models (GLMs) and generalized additive models (GAM) to analyze data from individual participants in three published studies (N = 154, 73 and 31), and compare this with results from the conventional POI averaging approach, and with laterality assessed using fMRI (N = 31). The GLM approach was based on classic fMRI analysis that includes a hemodynamic response function as a predictor; the GAM approach estimated the response function from the data, including a term for time relative to epoch start (simple GAM), plus a categorical index corresponding to individual epochs (complex GAM). Individual estimates of the fTCD laterality index are similar across all methods, but error of measurement is lowest using complex GAM. Reliable identification of cases of bilateral language appears to be more accurate with complex GAM. We also show that the GAM-based approach can be used to efficiently analyze more complex designs that incorporate interactions between tasks