Advancing the Future of Nursing: A Report by the Building Academic Geriatric Nursing

In the United States, the number of older adults will double during the next 25 years (United States Census Bureau, 2008). This dramatic demographic shift is changing the landscape of health care practice as more people live longer with multiple chronic conditions. To better prepare nurses to care for this future population, the John A. Hartford Foundation partnered with the American Academy of Nursing in 2000 to launch the Building Academic Geriatric Nursing Capacity (BAGNC) program. Since that time, 251 scholarships and fellowships have been awarded to nurses to advance geriatric nursing education, research, and practice. In 2009, the BAGNC nurse scholars and fellows formed an alumni organization to expand and continue their leadership development through peer networking and mentored policy initiatives. The BAGNC Alumni organization represents an elite set of new leaders in gerontological nursing to advance geriatric nursing education, research, and practice (Fagin, 2012). To this end, at the 2011 Council for Advancement of Nursing Science\u27s Special Topics Meeting, the BAGNC Alumni presented their ongoing and completed projects that relate to the Institute of Medicine (2011) (IOM) report The Future of Nursing: Leading Change, Advancing Health. Summaries of the individual presentations from this panel addressed the four key IOM messages and are presented in this article to highlight the action of these scholars and fellows

Retirements of Coal and Oil Power Plants in California: Association With Reduced Preterm Birth Among Populations Nearby.

Coal and oil power plant retirements reduce air pollution nearby, but few studies have leveraged these natural experiments for public health research. We used California Department of Public Health birth records and US Energy Information Administration data from 2001-2011 to evaluate the relationship between the retirements of 8 coal and oil power plants and nearby preterm (gestational age of <37 weeks) birth. We conducted a difference-in-differences analysis using adjusted linear mixed models that included 57,005 births-6.3% of which were preterm-to compare the probability of preterm birth before and after power plant retirement among mothers residing within 0-5 km and 5-10 km of the 8 power plants. We found that power plant retirements were associated with a decrease in the proportion of preterm birth within 5 km (-0.019, 95% CI: -0.031, -0.008) and 5-10 km (-0.015, 95% CI: -0.024, -0.007), controlling for secular trends with mothers living 10-20 km away. For the 0-5-km area, this corresponds to a reduction in preterm birth from 7.0% to 5.1%. Subgroup analyses indicated a potentially larger association among non-Hispanic black and Asian mothers than among non-Hispanic white and Hispanic mothers and no differences in educational attainment. Future coal and oil power plant retirements may reduce preterm birth among nearby populations

Quantitation of drug sensitivity by human metastatic melanoma colony-forming units.

We measured the effect of 6 standard (Adriamycin, BCNU, DTIC, melphalan, vinblastine, actinomycin D) and 3 Phase II agents (cis-platinum, vindesine, AMSA) on melanoma colony-forming units (CFU) in soft agar from biopsies of 50 patients with metastatic melanoma. Melanoma CFU demonstrated marked heterogeneity in chemosensitivity to these 9 drugs. Reduction in survival of CFU below 38% at one-tenth the pharmacologically achievable 1h concentration (our operational definition of chemosensitivity) was obtained in only 19% of 200 in vitro trials, and was usually the same whether or not patients had been exposed to prior chemotherapy, suggesting that melanoma CFU are inherently resistant to presently available chemotherapeutic drugs. The soft-agar assay was 86% accurate (25/29 cases) in identifying drugs to which the tumour was resistant in vivo, and 63% accurate (12/19 trials) in identifying drugs to which the tumour was clinically sensitive, counting mixed responses as responses. In contrast, if mixed responses were classified as progressive disease, the accuracy of identification of sensitivity fell to 42% (8/19 trials). These investigations furnish a quantitative description of the chemosensitivity of human metastatic melanoma CFU. Additionally, these studies serve as a useful step towards the development of an in vitro chemosensitivity test for human melanoma, and provide an operational quantitative basis for further exploration of in vitro-directed therapy in metastatic neoplasms

An Integrated Process for Co-Developing and Implementing Written and Computable Clinical Practice Guidelines

The goal of this article is to describe an integrated parallel process for the co-development of written and computable clinical practice guidelines (CPGs) to accelerate adoption and increase the impact of guideline recommendations in clinical practice. From February 2018 through December 2021, interdisciplinary work groups were formed after an initial Kaizen event and using expert consensus and available literature, produced a 12-phase integrated process (IP). The IP includes activities, resources, and iterative feedback loops for developing, implementing, disseminating, communicating, and evaluating CPGs. The IP incorporates guideline standards and informatics practices and clarifies how informaticians, implementers, health communicators, evaluators, and clinicians can help guideline developers throughout the development and implementation cycle to effectively co-develop written and computable guidelines. More efficient processes are essential to create actionable CPGs, disseminate and communicate recommendations to clinical end users, and evaluate CPG performance. Pilot testing is underway to determine how this IP expedites the implementation of CPGs into clinical practice and improves guideline uptake and health outcomes

The Origin of the Virgo Stellar Substructure

We present three-dimensional space velocities of stars selected to be consistent with membership in the Virgo stellar substructure. Candidates were selected from SA 103, a single 40x40 arcmin field from our proper motion (PM) survey in Kapteyn's Selected Areas (SAs), based on the PMs, SDSS photometry, and follow-up spectroscopy of 215 stars. The signature of the Virgo substructure is clear in the SDSS color-magnitude diagram (CMD) centered on SA 103, and 16 stars are identified that have high Galactocentric-frame radial velocities (V_GSR > 50 km/s) and lie near the CMD locus of Virgo. The implied distance to the Virgo substructure from the candidates is 14+/-3 kpc. We derive mean kinematics from these 16 stars, finding a radial velocity V_GSR = 153+/-22 km/s and proper motions (mu_alpha*cos(delta), mu_delta) = (-5.24, -0.91)+/-(0.43, 0.46) mas/yr. From the mean kinematics of these members, we determine that the Virgo progenitor was on an eccentric (e ~ 0.8) orbit that recently passed near the Galactic center (pericentric distance R_p ~ 6 kpc). This destructive orbit is consistent with the idea that the substructure(s) in Virgo originated in the tidal disruption of a Milky Way satellite. N-body simulations suggest that the entire cloud-like Virgo substructure (encompassing the "Virgo Overdensity" and the "Virgo Stellar Stream") is likely the tidal debris remnant from a recently-disrupted massive (~10^9 M_sun) dwarf galaxy. The model also suggests that some other known stellar overdensities in the Milky Way halo (e.g., the Pisces Overdensity and debris near NGC 2419 and SEGUE 1) are explained by the disruption of the Virgo progenitor.Comment: Accepted to ApJ; preprint format, 41 pages, 17 figures (some with degraded resolution). Full-resolution version (in emulateapj format) available at http://homepages.rpi.edu/~carlij/virgo_paper/carlin_etal2012_virgo.pd

Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery of 187 Novel Risk Variants

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas