Rejuvenating UDEL

Abstract The purpose of my poster is to illustrate the development of a number of resources designed to aid in the learning and teaching of information skills, either as part of a skills session in the library or pc lab, or as part of self-directed study. It will highlight the aims of the Information Skills project team at the University of Derby, along with a timeline for the project to the present day. Included will be information on the tutorials currently completed using the Adobe Captivate software, with screenshots of same to show some of the creative standards agreed upon. As a starting point for the project we used the library catalogue as the 'test' piece which was trialled among the student body, feedback from which led to the consolidation of the standards employed in all demonstrations as well as to modifications to the original example tutorial. Examples of some of the questions asked during the trial will be included on the poster to illustrate what feedback we were looking for. The poster will also include projections for the future, highlighting the directions in which we look to take the project as it becomes incorporated into the daily work of subject librarians at the University. It will also indicate how we plan to measure the impact of these resources on the student experience and use the subsequent feedback to further develop and improve those resources for the future. Handouts detailing key points from the poster will be available for colleagues to take away with them, and if possible a demonstration of one of the tutorials will also take place. Two of the tutorials are publically available without VLE access and those links will be included on the handout for colleagues to look at in their own time

Raleigh, Wake County : an action-oriented community diagnosis for people living with disabilities in Raleigh, NC

Universal Disability Advocates (UDA) is a grassroots, nonprofit organization in Raleigh, N.C. that advocates for people of all ages and abilities in the community. Through a partnership with the North Carolina Office on Disability and Health, UDA invited a team of six students from the UNC School of Public Health in Chapel Hill, NC to conduct an Action-Oriented Community Diagnosis (AOCD) of people living with disabilities in Raleigh. Two UDA members and two employees of the NC Office on Disability and Health agreed to serve as preceptors and mentors for the project and as liaisons between the students and the community. The team first entered the community in October 2003 and the AOCD process was completed following a community forum held in April 2004. The goal of an Action Oriented Community Diagnosis (AOCD) is to gather, analyze, and summarize the perspectives of community members and service providers in a community for the purpose of creating a complete vision of the community’s strengths, challenges, and existing resources on which to build. The AOCD process is designed to culminate in a Community Forum where all community stakeholders come together to create action steps to improve existing situations. The team in Raleigh began the AOCD process by examining secondary data and attending community meetings and events. The team then conducted 32 interviews and 2 focus groups with service providers, individuals with disabilities, and family members of people with disabilities in Raleigh, and identified recurrent themes raised by interviewees. Following a thorough review of all interview transcripts, the team identified the most frequently recurring issues and strengths (called domains) raised by interviewees. The AOCD team then worked with a planning group of community members and service providers to prioritize the recurrent domains. The most important and changeable issues identified by people with disabilities in Raleigh included: the accessibility and affordability of housing and Raleigh; issues of public transportation in Raleigh, the Raleigh built environment, specifically, the accessibility of sidewalks, parking lots and buildings; community awareness in Raleigh and communication with people with disabilities; the unemployment and underemployment of people with disabilities in Raleigh; and the challenges around obtaining services in Raleigh. Each of these domains was the topic of a small group discussion at the Raleigh Community Forum. The Raleigh Community Forum was held on Monday April 19th from 6:00 to 8:30 pm at the Hudson Memorial Presbyterian Church on Six Forks Road in Raleigh. Twenty-five community members and service providers attended the forum. After opening remarks, a brief overview of the methodology of the AOCD process and a detailed description of the prioritized issues for discussion, forum attendees divided into small groups. Small group discussions surrounding each domain led to the generation and prioritization of action steps for the future. Action steps resulting from the small group discussion on the accessibility and affordability of housing in Raleigh included: to attend and speak at at least one builders convention to raise awareness about the needs of people living with disabilities and access to affordable, accessible housing; to raise awareness among the general public through publicity and collaborations with existing organizations like Universal Disability Advocates, The Raleigh Mayor’s Committee, Center for Independent Living, and the Center for Universal Design at North Carolina State University; to include housing information on an existing disability advocacy website now in a design phase; and, to, in the long-term, build a visitable housing complex in accordance with the principles of universal design. Following a discussion on the Raleigh built environment, specifically, the accessibility of sidewalks, parking lots, and buildings, an action step was to form an email group that will arrive at action steps involving collaboration with other organizations. Resulting from a discussion on community awareness in Raleigh and communication issues with health care providers, action steps were to: attend existing community activities, such as health fairs, to increase awareness about this uses; to create a “tips for consumers” brochure focusing on how to advocate for ones’ own health needs; and to continue providing continuing education courses for health care professionals regarding communication with people with disabilities. Action steps resulting from the small group discussion on the unemployment and underemployment of people with disabilities in Raleigh were to: advocate at the state and federal levels by contacting legislators and the governor to ask: Where do people with disabilities fit into your action plans? And is there an action plan for employment for people with disabilities?; to educate the community through existing organizations, to register to vote, and to learn how to effectively advocate for equal employment; and, to educate the community about taking legal action through the Americans with Disabilities Act when necessary. As a discussion of issues of public transportation in Raleigh did not occur during the community forum, no action steps were created. In addition to bringing together Raleigh community members and service providers in communication about the future, the AOCD team involved in this project was particularly interested in the influence of the Americans with Disabilities Act on the presence and functions of community among adults living with disabilities in Raleigh, N.C. Through their research, AOCD team members identified dramatically different views on the existence of a Raleigh community of people with disabilities. This document, which complies information collected through interviews, secondary data sources, and observations of team members, is written with the understanding that the definition of “community of people living with disabilities” used by the team is meaningful and a truth to some, while not believed to exist nor advocated for by others. The definition of a cross-disability community is considered by some to be the critical foundation for continued efforts to secure rights for people living with disabilities. For others, defining people with disabilities as a community is perceived as furthering the historical segregation of this group from the rest of society. For still others, community is defined within the boundaries of one’s own disability and/or geographical or relational factors. This AOCD document is intended to serve as a resource to the people of Raleigh. The document is organized into six sections: an Introduction to the Project, Findings from Secondary Data, Results, Community Forum, Methodology, and Conclusions and Next Steps. The team presents this document in the hope that it will contribute to the existing body of knowledge supporting and advancing people living with disabilities in Raleigh, North Carolina. It has been the team’s privilege to learn from so many people working to make Raleigh a more inclusive community for people with disabilities, and the team hopes the action steps for change generated by the community during this project will compliment existing work or serve as a catalyst for new action.Master of Public Healt

Lynch Syndrome-Associated Extracolonic Tumors Are Rare in Two Extended Families With the Same EPCAM Deletion

The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some families were found to show a LS phenotype without an identified MMR mutation, although there was microsatellite instability and absence of MSH2 expression by immunohistochemistry. Studies of a subset of these families found a deletion at the 3′ end of the epithelial cell adhesion molecule (EPCAM) gene, causing transcription read-through resulting in silencing of MSH2 through hypermethylation of its promoter. The tumor spectrum of such families appears to differ from classical LS

High-mass star-forming cloud G0.38+0.04 in the Galactic center dust ridge contains H2CO and SiO masers

We have discovered a new H2CO (formaldehyde) 11,0−11,1 4.82966 GHz maser in Galactic center Cloud C, G0.38+0.04. At the time of acceptance, this is the eighth region to contain an H2CO maser detected in the Galaxy. Cloud C is one of only two sites of confirmed high-mass star formation along the Galactic center ridge, affirming that H2CO masers are exclusively associated with high-mass star formation. This discovery led us to search for other masers, among which we found new SiO vibrationally excited masers, making this the fourth star-forming region in the Galaxy to exhibit SiO maser emission. Cloud C is also a known source of CH3OH Class-II and OH maser emission. There are now two known regions that contain both SiO and H2CO masers in the CMZ, compared to two SiO and six H2CO in the Galactic disk, while there is a relative dearth of H2O and CH3OH Class-II masers in the CMZ. SiO and H2CO masers may be preferentially excited in the CMZ, perhaps because of higher gas-phase abundances from grain destruction and heating, or alternatively H2O and CH3OH maser formation may be suppressed in the CMZ. In any case, Cloud C is a new testing ground for understanding maser excitation conditions

Development and implementation of a highly-multiplexed SNP array for genetic mapping in maritime pine and comparative mapping with loblolly pine

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are the most abundant source of genetic variation among individuals of a species. New genotyping technologies allow examining hundreds to thousands of SNPs in a single reaction for a wide range of applications such as genetic diversity analysis, linkage mapping, fine QTL mapping, association studies, marker-assisted or genome-wide selection. In this paper, we evaluated the potential of highly-multiplexed SNP genotyping for genetic mapping in maritime pine (<it>Pinus pinaster </it>Ait.), the main conifer used for commercial plantation in southwestern Europe.</p> <p>Results</p> <p>We designed a custom GoldenGate assay for 1,536 SNPs detected through the resequencing of gene fragments (707 <it>in vitro </it>SNPs/Indels) and from Sanger-derived Expressed Sequenced Tags assembled into a unigene set (829 <it>in silico </it>SNPs/Indels). Offspring from three-generation outbred (G2) and inbred (F2) pedigrees were genotyped. The success rate of the assay was 63.6% and 74.8% for <it>in silico </it>and <it>in vitro </it>SNPs, respectively. A genotyping error rate of 0.4% was further estimated from segregating data of SNPs belonging to the same gene. Overall, 394 SNPs were available for mapping. A total of 287 SNPs were integrated with previously mapped markers in the G2 parental maps, while 179 SNPs were localized on the map generated from the analysis of the F2 progeny. Based on 98 markers segregating in both pedigrees, we were able to generate a consensus map comprising 357 SNPs from 292 different loci. Finally, the analysis of sequence homology between mapped markers and their orthologs in a <it>Pinus taeda </it>linkage map, made it possible to align the 12 linkage groups of both species.</p> <p>Conclusions</p> <p>Our results show that the GoldenGate assay can be used successfully for high-throughput SNP genotyping in maritime pine, a conifer species that has a genome seven times the size of the human genome. This SNP-array will be extended thanks to recent sequencing effort using new generation sequencing technologies and will include SNPs from comparative orthologous sequences that were identified in the present study, providing a wider collection of anchor points for comparative genomics among the conifers.</p

Checkpoint Signaling, Base Excision Repair, and PARP Promote Survival of Colon Cancer Cells Treated with 5-Fluorodeoxyuridine but Not 5-Fluorouracil

The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca