Change-point model on nonhomogeneous Poisson processes with application in copy number profiling by next-generation DNA sequencing

We propose a flexible change-point model for inhomogeneous Poisson Processes, which arise naturally from next-generation DNA sequencing, and derive score and generalized likelihood statistics for shifts in intensity functions. We construct a modified Bayesian information criterion (mBIC) to guide model selection, and point-wise approximate Bayesian confidence intervals for assessing the confidence in the segmentation. The model is applied to DNA Copy Number profiling with sequencing data and evaluated on simulated spike-in and real data sets.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS517 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A systematic review and meta-analysis on delaying surgery for urothelial carcinoma of bladder and upper tract urothelial carcinoma : Implications for the COVID19 pandemic and beyond

PurposeThe COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC.MethodsWe searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed.ResultsWe identified a total of 30 studies with 32,591 patients. Across 13 studies (n = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09-1.45, p = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies (n = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96-1.94, p = 0.08). For UTUC, 6 studies (n = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19-2.02, p = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50-4.37, p = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery.ConclusionsA delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy.Peer reviewe

Using RNase sequence specificity to refine the identification of RNA-protein binding regions

Massively parallel pyrosequencing is a high-throughput technology that can sequence hundreds of thousands of DNA/RNA fragments in a single experiment. Combining it with immunoprecipitation-based biochemical assays, such as cross-linking immunoprecipitation (CLIP), provides a genome-wide method to detect the sites at which proteins bind DNA or RNA. In a CLIP-pyrosequencing experiment, the resolutions of the detected protein binding regions are partially determined by the length of the detected RNA fragments (CLIP amplicons) after trimming by RNase digestion. The lengths of these fragments usually range from 50-70 nucleotides. Many genomic regions are marked by multiple RNA fragments. In this paper, we report an empirical approach to refine the localization of protein binding regions by using the distribution pattern of the detected RNA fragments and the sequence specificity of RNase digestion. We present two regions to which multiple amplicons map as examples to demonstrate this approach

Do individual differences in face recognition ability moderate the other ethnicity effect?

Individuals are better at recognizing faces from their own ethnic group compared with other ethnicity faces—the other-ethnicity effect (OEE). This finding is said to reflect differences in experience and familiarity to faces from other ethnicities relative to faces corresponding with the viewers' ethnicity. However, own-ethnicity face recognition performance ranges considerably within a population, from very poor to extremely good. In addition, within-population recognition performance on other-ethnicity faces can also vary considerably with some individuals being classed as “other ethnicity face blind” (Wan et al., 2017). Despite evidence for considerable variation in performance within population for faces of both types, it is currently unclear whether the magnitude of the OEE changes as a function of this variability. By recruiting large-scale multinational samples, we investigated the size of the OEE across the full range of own and other ethnicity face performance while considering measures of social contact. We find that the magnitude of the OEE is remarkably consistent across all levels of within-population own- and other-ethnicity face recognition ability, and this pattern was unaffected by social contact measures. These findings suggest that the OEE is a persistent feature of face recognition performance, with consequences for models built around very poor, and very good face recognizers

Dynamical Measurements of Black Hole Masses in Four Brightest Cluster Galaxies at 100 Mpc

We present stellar kinematics and orbit superposition models for the central regions of four Brightest Cluster Galaxies (BCGs), based upon integral-field spectroscopy at Gemini, Keck, and McDonald Observatories. Our integral-field data span radii from < 100 pc to tens of kpc. We report black hole masses, M_BH, of 2.1 +/- 1.6 x 10^10 M_Sun for NGC 4889, 9.7 + 3.0 - 2.6 x 10^9 M_Sun for NGC 3842, and 1.3 + 0.5 - 0.4 x 10^9 M_Sun for NGC 7768. For NGC 2832 we report an upper limit of M_BH < 9 x 10^9 M_Sun. Stellar orbits near the center of each galaxy are tangentially biased, on comparable spatial scales to the galaxies' photometric cores. We find possible photometric and kinematic evidence for an eccentric torus of stars in NGC 4889, with a radius of nearly 1 kpc. We compare our measurements of M_BH to the predicted black hole masses from various fits to the relations between M_BH and stellar velocity dispersion, luminosity, or stellar mass. The black holes in NGC 4889 and NGC 3842 are significantly more massive than all dispersion-based predictions and most luminosity-based predictions. The black hole in NGC 7768 is consistent with a broader range of predictions.Comment: 24 pages, 18 figures. Accepted for publication in Ap

Integrated Pockels Laser

The development of integrated semiconductor lasers has miniaturized traditional bulky laser systems, enabling a wide range of photonic applications. A progression from pure III-V based lasers to III-V/external cavity structures has harnessed low-loss waveguides in different material systems, leading to significant improvements in laser coherence and stability. Despite these successes, however, key functions remain absent. In this work, we address a critical missing function by integrating the Pockels effect into a semiconductor laser. Using a hybrid integrated III-V/Lithium Niobate structure, we demonstrate several essential capabilities that have not existed in previous integrated lasers. These include a record-high frequency modulation speed of 2 exahertz/s (2.0$\times$10$^{18}$ Hz/s) and fast switching at 50 MHz, both of which are made possible by integration of the electro-optic effect. Moreover, the device co-lases at infrared and visible frequencies via the second-harmonic frequency conversion process, the first such integrated multi-color laser. Combined with its narrow linewidth and wide tunability, this new type of integrated laser holds promise for many applications including LiDAR, microwave photonics, atomic physics, and AR/VR

Mental Health Problems among Children One-Year after Sichuan Earthquake in China: A Follow-up Study

Background: On May 12, 2008, a destructive earthquake registering 8.0 on the Richter scale struck Sichuan Province, southwest China. Beichuan County was the epicenter which was one of the areas nearly completely destroyed by the earthquake. In Beichuan, about 15000 people died and 3000 people were missing. Specially, the earthquake took 1587 students&#39; and 214 teachers&#39; lives from the elementary and middle schools there. The main purpose of the study was to provide a better understanding of mental health problems and associated risk factors among children after earthquake

Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers

Resistance to oestrogen-deprivation therapy is common in oestrogen-receptor-positive (ER+) breast cancer. To better understand the contributions of tumour heterogeneity and evolution to resistance, here we perform comprehensive genomic characterization of 22 primary tumours sampled before and after 4 months of neoadjuvant aromatase inhibitor (NAI) treatment. Comparing whole-genome sequencing of tumour/normal pairs from the two time points, with coincident tumour RNA sequencing, reveals widespread spatial and temporal heterogeneity, with marked remodelling of the clonal landscape in response to NAI. Two cases have genomic evidence of two independent tumours, most obviously an ER− ‘collision tumour', which was only detected after NAI treatment of baseline ER+ disease. Many mutations are newly detected or enriched post treatment, including two ligand-binding domain mutations in ESR1. The observed clonal complexity of the ER+ breast cancer genome suggests that precision medicine approaches based on genomic analysis of a single specimen are likely insufficient to capture all clinically significant information