Pathology Informatics Essentials for Residents: A Flexible Informatics Curriculum Linked to Accreditation Council for Graduate Medical Education Milestones (a secondary publication)*

Context: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. Objective: To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. Design: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. Results: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http:// www.apcprods.org/PIER (accessed April 6, 2016). Conclusions: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time

The ITGAV rs3738919 variant and susceptibility to rheumatoid arthritis in four Caucasian sample sets

INTRODUCTION: Angiogenesis is an important process in the development of destructive synovial pannus in rheumatoid arthritis (RA). The ITGAV +gene encodes a cell cycle-associated antigen, integrin alphanubeta 3, which plays a role in RA angiogenesis. Previously, two independent studies identified an association between the major allele of the ITGAV single-nucleotide polymorphism (SNP) rs3738919 and RA. We therefore tested this association in an independent study using New Zealand (NZ) and Oxford (UK) RA case control samples. METHODS: We compared genotype frequencies in 740 NZ Caucasian RA patients and 553 controls genotyped for rs3738919, using a polymerase chain reaction-restriction fragment length polymorphism assay. A TaqMan genotyping SNP assay was used to type 713 Caucasian RA patients and 515 control samples from Oxford for the rs3738919 variant. Association of rs3738919 with RA was tested in these two sample sets using the chi-square goodness-of-fit test. The Mantel-Haenszel test was used to perform a meta-analysis, combining the genetic results from four independent Caucasian case control cohorts, consisting of 3,527 cases and 4,126 controls. Haplotype analysis was also performed using SNPs rs3911238, rs10174098 and rs3738919 in the Wellcome Trust Case Control Consortium, NZ and Oxford case control samples. RESULTS: We found no evidence for association between ITGAV and RA in either the NZ or Oxford sample set (odds ratio [OR] = 0.88, P(allelic) = 0.11 and OR = 1.18, P(allelic) = 0.07, respectively). Inclusion of these data in a meta-analysis (random effects) of four independent cohorts (3,527 cases and 4,126 controls) weakens support for the hypothesis that rs3738919 plays a role in the development of RA (OR(combined) = 0.92, 95% confidence interval 0.80 to 1.07; P = 0.29). No consistent haplotype associations were evident. CONCLUSIONS: Association of ITGAV SNP rs7378919 with RA was not replicated in NZ or Oxford case control sample sets. Meta-analysis of these and previously published data lends limited support for a role for the ITGAV in RA in Caucasians of European ancestry

Pressure dependent electronic properties of MgO polymorphs: A first-principles study of Compton profiles and autocorrelation functions

The first-principles periodic linear combination of atomic orbitals method within the framework of density functional theory implemented in the CRYSTAL06 code has been applied to explore effect of pressure on the Compton profiles and autocorrelation functions of MgO. Calculations are performed for the B1, B2, B3, B4, B8_1 and h-MgO polymorphs of MgO to compute lattice constants and bulk moduli. The isothermal enthalpy calculations predict that B4 to B8_1, h-MgO to B8_1, B3 to B2, B4 to B2 and h-MgO to B2 transitions take place at 2, 9, 37, 42 and 64 GPa respectively. The high pressure transitions B8_1 to B2 and B1 to B2 are found to occur at 340 and 410 GPa respectively. The pressure dependent changes are observed largely in the valence electrons Compton profiles whereas core profiles are almost independent of the pressure in all MgO polymorphs. Increase in pressure results in broadening of the valence Compton profiles. The principal maxima in the second derivative of Compton profiles shifts towards high momentum side in all structures. Reorganization of momentum density in the B1 to B2 structural phase transition is seen in the first and second derivatives before and after the transition pressure. Features of the autocorrelation functions shift towards lower r side with increment in pressure.Comment: 19 pages, 8 figures, accepted for publication in Journal of Materials Scienc

Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance

INTRODUCTION: The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus. METHODS: A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA. RESULTS: No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR)=0.95 (0.80 to 1.12), P=0.54), or rs17388568 (OR=1.03 (0.90 to 1.19), P=0.65) or rs907715 (OR=0.98 (0.86 to 1.12), P=0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR=0.86 (0.82 to 0.91), P=8.8x10(-8), P=2.1x10(-8) including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR=1.03, (0.98 to 1.09); P=0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR=0.93 (0.87 to 1.00), P=0.07). However, this trend was not independent of the association at rs6822844. CONCLUSIONS: The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P ≤ 5x10(-8)) level of support for association with RA. As for most other autoimmune diseases, with the notable exception of T1D, rs6822844 is the dominant association in the locus. The KIAA1109-TENR-IL2-IL21 locus also confers susceptibility to other autoimmune phenotypes with a heterogeneous pattern of association

Why do women invest in pre-pregnancy health and care? A qualitative investigation with women attending maternity services

Background Despite the importance attributed to good pre-pregnancy care and its potential to improve pregnancy and child health outcomes, relatively little is known about why women invest in pre-pregnancy health and care. We sought to gain insight into why women invested in pre-pregnancy health and care. Methods We carried out 20 qualitative in-depth interviews with pregnant or recently pregnant women who were drawn from a survey of antenatal clinic attendees in London, UK. Interviewees were purposively sampled to include high and low investors in pre-pregnancy health and care, with variation in age, partnership status, ethnicity and pre-existing medical conditions. Data analysis was conducted using the Framework method. Results We identified three groups in relation to pre-pregnancy health and care: 1) The “prepared” group, who had high levels of pregnancy planning and mostly positive attitudes to micronutrient supplementation outside of pregnancy, carried out pre-pregnancy activities such as taking folic acid and making changes to diet and lifestyle. 2) The “poor knowledge” group, who also had high levels of pregnancy planning, did not carry out pre-pregnancy activities and described themselves as having poor knowledge. Elsewhere in their interviews they expressed a strong dislike of micronutrient supplementation. 3) The “absent pre-pregnancy period” group, had the lowest levels of pregnancy planning and also expressed anti-supplement views. Even discussing the pre-pregnancy period with this group was difficult as responses to questions quickly shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all groups. Conclusion Different pre-pregnancy care approaches are likely to be needed for each of the groups. Among the “prepared” group, who were proactive and receptive to health messages, greater availability of information and better response from health professionals could improve the range of pre-pregnancy activities carried out. Among the “poor knowledge” group, better response from health professionals might yield greater uptake of pre-pregnancy information. A different, general health strategy might be more appropriate for the “absent pre-pregnancy period” group. The fact that general attitudes to micronutrient supplementation were closely related to whether or not women invested in pre-pregnancy health and care was an unanticipated finding and warrants further investigation.This report is independent research commissioned and funded by the Department of Health Policy Research Programme Pre-Pregnancy Health and Care in England: Exploring Implementation and Public Health Impact, 006/0068

DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

Evidence and Policy in Aid-Dependent Settings

This chapter examines how the political dynamics of aid relationships can affect the use of evidence within health policymaking. Empirical examples from Cambodia, Ethiopia and Ghana illustrate how relationships between national governments and donor agencies influence the ways in which evidence is generated, selected, or utilised to inform policymaking. We particularly consider how relationships with donors influence the underlying systems and processes of evidence use. We find a number of issues affecting which bodies or forms of evidence are taken to be policy relevant, including: levels of local technical capacity to utilise or synthesise evidence; differing stakeholder framing of issues; and the influence of non-state actors on sector-wide systems of agenda setting. The chapter also reflects on some of the key governance implications of these arrangements in which global actors promote forms of evidence use – often under a banner of technical efficiency – with limited consideration for local representation or accountability

Community shift of ammonia-oxidizing bacteria along an anthropogenic pollution gradient from the Pearl River Delta to the South China Sea

The phylogenetic diversity and abundance of ammonia-oxidizing beta-proteobacteria (beta-AOB) was analyzed along an anthropogenic pollution gradient from the coastal Pearl River Delta to the South China Sea using the ammonia monooxygenase subunit A (amoA) gene. Along the gradient from coastal to the open ocean, the phylogenetic diversity of the dominant genus changed from Nitrosomonas to Nitrosospira, indicating the niche specificity by these two genera as both salinity and anthropogenic influence were major factors involved. The diversity of bacterial amoA gene was also variable along the gradient, with the highest in the deep-sea sediments, followed by the marshes sediments and the lowest in the coastal areas. Within the Nitrosomonas-related clade, four distinct lineages were identified including a putative new one (A5-16) from the different sites over the large geographical area. In the Nitrosospira-related clade, the habitat-specific lineages to the deep-sea and coastal sediments were identified. This study also provides strong support that Nitrosomonas genus, especially Nitrosomonas oligotropha lineage (6a) could be a potential bio-indicator species for pollution or freshwater/wastewater input into coastal environments. A suite of statistical analyses used showed that water depth and temperature were major factors shaping the community structure of beta-AOB in this study area

Increased Level of Extracellular ATP at Tumor Sites: In Vivo Imaging with Plasma Membrane Luciferase

There is growing awareness that tumour cells build up a "self-advantageous" microenvironment that reduces effectiveness of anti-tumour immune response. While many different immunosuppressive mechanisms are likely to come into play, recent evidence suggests that extracellular adenosine acting at A2A receptors may have a major role in down-modulating the immune response as cancerous tissues contain elevated levels of adenosine and adenosine break-down products. While there is no doubt that all cells possess plasma membrane adenosine transporters that mediate adenosine uptake and may also allow its release, it is now clear that most of extracellularly-generated adenosine originates from the catabolism of extracellular ATP. METHODOLOGY/PRINCIPAL FINDINGS: Measurement of extracellular ATP is generally performed in cell supernatants by HPLC or soluble luciferin-luciferase assay, thus it generally turns out to be laborious and inaccurate. We have engineered a chimeric plasma membrane-targeted luciferase that allows in vivo real-time imaging of extracellular ATP. With this novel probe we have measured the ATP concentration within the tumour microenvironment of several experimentally-induced tumours. CONCLUSIONS/SIGNIFICANCE: Our results show that ATP in the tumour interstitium is in the hundreds micromolar range, while it is basically undetectable in healthy tissues. Here we show that a chimeric plasma membrane-targeted luciferase allows in vivo detection of high extracellular ATP concentration at tumour sites. On the contrary, tumour-free tissues show undetectable extracellular ATP levels. Extracellular ATP may be crucial for the tumour not only as a stimulus for growth but also as a source of an immunosuppressive agent such as adenosine. Our approach offers a new tool for the investigation of the biochemical composition of tumour milieu and for development of novel therapies based on the modulation of extracellular purine-based signalling