Winter residency and site association in the critically endangered North East Atlantic spurdog (Squalus acanthias)

Identification and incorporation of residential behaviour into elasmobranch management plans has the potential to substantially increase their effectiveness by identifying sites where Marine Protected Areas (MPAs) might be used to help conserve species with high migratory potential. There is evidence that spurdog (Squalus acanthias) displays site association in some parts of its global distribution, but this has currently not been shown within the North East Atlantic where it is critically endangered. Here we investigate the movements of electronically tagged spurdog within Loch Etive, a sea loch on the west coast of Scotland. Archival data storage tags (DSTs), that recorded depth and temperature, revealed that mature female spurdog over wintered within the loch, restricting their movements to the upper basin, and remaining either in the loch or the local vicinity for the rest of the year. This finding was supported by evidence for limited movements from conventional mark/recapture data and acoustically tagged individual spurdog. Some of the movements between the loch basins appear to be associated with breeding and parturition events. This high level of site association suggests that spatial protection of the loch would aid the conservation of different age and sex classes of spurdog

FIMO: scanning for occurrences of a given motif

Summary: A motif is a short DNA or protein sequence that contributes to the biological function of the sequence in which it resides. Over the past several decades, many computational methods have been described for identifying, characterizing and searching with sequence motifs. Critical to nearly any motif-based sequence analysis pipeline is the ability to scan a sequence database for occurrences of a given motif described by a position-specific frequency matrix

Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts

Our current understanding of how DNA is packed in the nucleus is most accurate at the fine scale of individual nucleosomes and at the large scale of chromosome territories. However, accurate modeling of DNA architecture at the intermediate scale of ∼50 kb-10 Mb is crucial for identifying functional interactions among regulatory elements and their target promoters. We describe a method, Fit-Hi-C, that assigns statistical confidence estimates to mid-range intra-chromosomal contacts by jointly modeling the random polymer looping effect and previously observed technical biases in Hi-C data sets. We demonstrate that our proposed approach computes accurate empirical null models of contact probability without any distribution assumption, corrects for binning artifacts, and provides improved statistical power relative to a previously described method. High-confidence contacts identified by Fit-Hi-C preferentially link expressed gene promoters to active enhancers identified by chromatin signatures in human embryonic stem cells (ESCs), capture 77% ofRNA polymerase II-mediated enhancer-promoter interactions identified using ChIA-PET in mouse ESCs, and confirm previously validated, cell line-specific interactions in mouse cortex cells. We observe that insulators and heterochromatin regions are hubs for high-confidence contacts, while promoters and strong enhancers are involved in fewer contacts. We also observe that binding peaks of master pluripotency factors such as NANOG and POU5F1 are highly enriched in high-confidence contacts for human ESCs. Furthermore, we show that pairs of loci linked by high-confidence contacts exhibit similar replication timing in human and mouse ESCs and preferentially lie within the boundaries of topological domains for human and mouse cell lines

The 2023 CHCF California Health Policy Survey

California is home to nearly 40 million people of different incomes, ages, and racial and ethnic backgrounds, and who live in different regions. Every year since 2019, the California Health Care Foundation has conducted a representative, statewide survey of residents' views and experiences on a variety of health care topics, some of which are tracked to detect meaningful shifts over time.The California Health Care Foundation and NORC at the University of Chicago, a nonpartisan research organization, conducted the survey again in late 2022. Results are reported and, where applicable, compared to the prior annual survey, which was conducted in late 2021.Key findings from this year's survey include:Health care costs. Like prior years, half of Californians (52%) report skipping or delaying health care due to cost in the past 12 months.  Of those who skipped or delayed care, half of them (50%) say their condition got worse as a result.Medical debt. More than 1 in 3 (36%) report having medical debt, and of those, 1 in 5 (19%) report owing $5,000 or more. Californians with lower incomes (52%) are more likely than those with higher incomes (30%) to report medical debt

Quantifying similarity between motifs

A common question within the context of de novo motif discovery is whether a newly discovered, putative motif resembles any previously discovered motif in an existing database. To answer this question, we define a statistical measure of motif-motif similarity, and we describe an algorithm, called Tomtom, for searching a database of motifs with a given query motif. Experimental simulations demonstrate the accuracy of Tomtom's E values and its effectiveness in finding similar motifs

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ? 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics.RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001).CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS

MEME Suite: tools for motif discovery and searching

The MEME Suite web server provides a unified portal for online discovery and analysis of sequence motifs representing features such as DNA binding sites and protein interaction domains. The popular MEME motif discovery algorithm is now complemented by the GLAM2 algorithm which allows discovery of motifs containing gaps. Three sequence scanning algorithms—MAST, FIMO and GLAM2SCAN—allow scanning numerous DNA and protein sequence databases for motifs discovered by MEME and GLAM2. Transcription factor motifs (including those discovered using MEME) can be compared with motifs in many popular motif databases using the motif database scanning algorithm Tomtom. Transcription factor motifs can be further analyzed for putative function by association with Gene Ontology (GO) terms using the motif-GO term association tool GOMO. MEME output now contains sequence LOGOS for each discovered motif, as well as buttons to allow motifs to be conveniently submitted to the sequence and motif database scanning algorithms (MAST, FIMO and Tomtom), or to GOMO, for further analysis. GLAM2 output similarly contains buttons for further analysis using GLAM2SCAN and for rerunning GLAM2 with different parameters. All of the motif-based tools are now implemented as web services via Opal. Source code, binaries and a web server are freely available for noncommercial use at http://meme.nbcr.net

Disempowered, passive and isolated: how teenage mothers’ postnatal inpatient experiences in the UK impact on the initiation and continuation of breastfeeding

Teenage mothers in the UK and other developed, English-speaking nations are among those least likely to breastfeed. Evidence suggests more young mothers intend to breastfeed than actually start, indicating that their post-birth experiences militate against initiating breastfeeding. We aimed to explore how the inpatient experiences of a group of young women who gave birth as teenagers influenced their feeding decisions and experiences, and ascertain their ideals for breastfeeding support. Six focus groups or interviews were conducted with 15 women aged 16-20 who had intended to breastfeed or breastfed. Women were recruited from teenage parent groups in Oxfordshire, UK. Ethical approval was obtained from the relevant authorities. Data was analysed inductively using a thematic approach. Three overriding themes of ‘postbirth experience on Labour Ward: disempowered and passive’; ‘the postnatal ward: alien, alone and exposed’; and ‘being there: a need for relational support’ were identified. Sub-themes on Labour Ward were ‘feelings at birth: ’so tired and so dazed’; ‘deliver, stitch, dress’ and ‘initiating feeding’. Participants described care that followed set routines, discouraging their initiating breastfeeding by compounding feelings of dependance and encouraging a passive role as midwives took control, often deciding when and how babies should be fed. Sub-themes on the postnatal ward were ‘an alien environment’; ‘feeling exposed and judged’ and ‘miscommunications’. The young mothers’ breastfeeding support requirements reflected those known to be desired by older women, but they particularly wanted guidance and esteem support to be provided by a health professional, while looking to their peers for emotional support