Curriculum Decisions: Assessing and Updating IS Curriculum

The increased level of accountability in higher education has prompted many vomputer-related programs to seek accreditation. As accrediting agencies continue to define and refine exactly what these degrees should entail, institutions struggle with the decisions of aligning their curriculum with a dynamic set of standards set by an outside agency, focusing on the needs identified by their own assessment data, or attempting to marry the two. This paper details how one institution completed comprehensive reviews of their curriculum under two different projects: Expanding Pathways for Educational Development and Information Technology Experiences, an NSF-funded research project investigation and examination of curriculum and regional needs and an ABET evaluation and site visit. The focus of this report is to inform others of local efforts that may be replicated on their campuses, share findings that may be of use to others in similarly situated circumstances, and add to the assessment and accreditation dialog

The impact of over 80 years of land cover changes on bee and wasp pollinator communities in England

Change in land cover is thought to be one of the key drivers of pollinator declines, and yet there is a dearth of studies exploring the relationships between historical changes in land cover and shifts in pollinator communities. Here, we explore, for the first time, land cover changes in England over more than 80 years, and relate them to concurrent shifts in bee and wasp species richness and community composition. Using historical data from 14 sites across four counties, we quantify the key land cover changes within and around these sites and estimate the changes in richness and composition of pollinators. Land cover changes within sites, as well as changes within a 1 km radius outside the sites, have significant effects on richness and composition of bee and wasp species, with changes in edge habitats between major land classes also having a key influence. Our results highlight not just the land cover changes that may be detrimental to pollinator communities, but also provide an insight into how increases in habitat diversity may benefit species diversity, and could thus help inform policy and practice for future land management

Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration

Pathological analysis of the nuclear proliferation biomarker Ki67 has multiple potential roles in breast and other cancers. However, clinical utility of the immunohistochemical (IHC) assay for Ki67 immunohistochemistry has been hampered by unacceptable between-laboratory analytical variability. The International Ki67 Working Group has conducted a series of studies aiming to decrease this variability and improve the evaluation of Ki67. This study tries to assess whether acceptable performance can be achieved on prestained core-cut biopsies using a standardized scoring method. Sections from 30 primary ER+ breast cancer core biopsies were centrally stained for Ki67 and circulated among 22 laboratories in 11 countries. Each laboratory scored Ki67 using three methods: (1) global (4 fields of 100 cells each); (2) weighted global (same as global but weighted by estimated percentages of total area); and (3) hot-spot (single field of 500 cells). The intraclass correlation coefficient (ICC), a measure of interlaboratory agreement, for the unweighted global method (0.87; 95% credible interval (CI): 0.81–0.93) met the prespecified success criterion for scoring reproducibility, whereas that for the weighted global (0.87; 95% CI: 0.7999–0.93) and hot-spot methods (0.84; 95% CI: 0.77–0.92) marginally failed to do so. The unweighted global assessment of Ki67 IHC analysis on core biopsies met the prespecified criterion of success for scoring reproducibility. A few cases still showed large scoring discrepancies. Establishment of external quality assessment schemes is likely to improve the agreement between laboratories further. Additional evaluations are needed to assess staining variability and clinical validity in appropriate cohorts of samples

Comparative Genomics of Emerging Human Ehrlichiosis Agents

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens

Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Abstract: Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary end point, decreased Ki67, occured in 12% of TNBC. In secondary end point analyses, HR deficiency was identified in 69% of TNBC with the mutational-signature-based HRDetect assay. Cancers with HRDetect mutational signatures of HR deficiency had a functional defect in HR, assessed by impaired RAD51 foci formation on end of treatment biopsy. Following rucaparib treatment there was no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identified activity of rucaparib, with end of treatment ctDNA levels suppressed by rucaparib in mutation-signature HR-deficient cancers. In ad hoc analysis, rucaparib induced expression of interferon response genes in HR-deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors

Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Abstract: Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary end point, decreased Ki67, occured in 12% of TNBC. In secondary end point analyses, HR deficiency was identified in 69% of TNBC with the mutational-signature-based HRDetect assay. Cancers with HRDetect mutational signatures of HR deficiency had a functional defect in HR, assessed by impaired RAD51 foci formation on end of treatment biopsy. Following rucaparib treatment there was no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identified activity of rucaparib, with end of treatment ctDNA levels suppressed by rucaparib in mutation-signature HR-deficient cancers. In ad hoc analysis, rucaparib induced expression of interferon response genes in HR-deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors

A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation to secondary sex ratio

Abstract: Background: Polychlorinated biphenyls (PCBs) are ubiquitous industrial chemicals that persist in the environment and in human fatty tissue. PCBs are related to a class of compounds known as dioxins, specifically 2,3,7,8-TCDD (tetrachloro-dibenzodioxin), which has been implicated as a cause of altered sex ratio, especially in relation to paternal exposures. Methods: In the 1960's, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20°C. For this study, samples were thawed and a total of eleven PCBs were determined in 399 specimens. Secondary sex ratio, or sex ratio at birth, was evaluated as a function of maternal serum concentrations using log-binomial and logistic regression, controlling for hormonally active medications taken during pregnancy. Results: The relative risk of a male birth decreased by 33% comparing women at the 90th percentile of total PCBs with women at the 10th percentile (RR = 0.67; 95% CI, 0.48–0.94; p = 0.02), or by approximately 7% for each 1 μg/L increase in total PCB concentration. Although some congener-specific associations with sex ratio were only marginally statistically significant, all nine PCB congeners with < 30% of samples below the LOQ showed the same direction of association, an improbable finding under the null hypothesis. Conclusion: Maternal exposure to PCBs may be detrimental to the success of male sperm or to the survival of male embryos. Findings could be due to contaminants, metabolites or PCBs themselves