Forests and Carbon: A Synthesis of Science, Management, and Policy for Carbon Sequestration in Forests

The goal of this volume is to provide guidance for land managers and policymakers seeking to understand the complex science and policy of forest carbon as it relates to tangible problems of forest management and the more abstract problems of addressing drivers of deforestation and negotiating policy frameworks for reducing CO2 emissions from forests. It is the culmination of three graduate seminars at the Yale School of Forestry & Environmental Studies focused on carbon sequestration in forest ecosystems and their role in addressing climate change

Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine

Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine

Variation in LPA Is Associated with Lp(a) Levels in Three Populations from the Third National Health and Nutrition Examination Survey

The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18×10−30). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.The Breast Cancer Association Consortium (BCAC), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), and the Ovarian Cancer Association Consortium (OCAC) that contributed breast, prostate, and ovarian cancer data analyzed in this study were in part funded by Cancer Research UK [C1287/A10118 and C1287/A12014 for BCAC; C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135 for PRACTICAL; and C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689 for OCAC]. Funding for the Collaborative Oncological Gene-environment Study (COGS) infrastructure came from: the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the US National Institutes of Health (CA128978) and the Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112), the US Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund [with donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07)]. Additional financial support for contributing studies is documented under Supplementary Financial Support.This is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/2159-8290.CD-15-122

Clickin’ in the Honors Classroom: Using Audience Response Systems to Facilitate Discussion and Decision-Making

In his 1988 book entitled The Media Lab: Inventing the Future at MIT, Stewart Brand makes the following observation: “Once a new technology rolls over you, if you’re not part of the steamroller, you’re part of the road” (9). One focus of this Forum on “Honors in the Digital Age” is the degree to which honors faculty and students are part of the steamroller or part of the road. Instructional technologies can be both boon and bane, and I will address both aspects of using “clickers” in the honors classroom. “Clickers” is the common or slang term for what is more formally known as interactive, computer- based Audience Response Systems (ARS) or Group Response Systems (GRS), which allow members of an audience/group (e.g., classroom learners) to respond to questions posed to them by “clicking” their preferred answer out on a hand-held device or response pad. Those posing the questions (e.g., teachers or discussion facilitators) can, within seconds, prompt the system to tally, summarize, and display results in a chart form (e.g., pie, bar, or graph) for all to view and consider

An Ethnographic Study of Keyboarding Instruction and Standardized Assessment

The purpose of this ethnographic study was to examine the relationship between focused keyboarding instruction and the required standardized assessments mandated by Federal and State authorities. Initial mandates required that the first assessment to be administered online would be the Writing Assessment by year 2014. The assessment given in school year 2012-2013 could have been given to students either online or continue for one more year in handwritten form. As of school year 2022-2023 all standardized assessments will be administered online. Keyboarding instruction in Tennessee had been part of the middle school curriculum in previous years but had for all intents and purposes been omitted when physical education, music, Spanish, and art classes were mandated to be added or increased. A Middle Tennessee school system made the decision to add a focused keyboarding instruction segment in some shape or form along with the decision to administer the writing assessment online. This decision was due to the realization that without some level of typing skill students might not display their actual writing ability otherwise. This study examined whether keyboarding skills affected online standardized assessments, i.e., does typing skill free students’ cognitive skills to produce a higher quality product on an assessment. It also examined whether focused keyboarding instruction needs to be included in a curriculum and at what age, developmental level, and grade level. Further research was recommended concerning whether advancements in rapidly development technology will replace the need for keyboarding skills entirely, and whether keyboarding skill will replace the need for handwriting in the future

Racioethnic Disparities in Endometrial Cancer Outcomes

Black women are twice as likely to die from endometrial cancer (EC) compared with white women. This represents one of the worst racioethnic disparities amongst all cancers globally. Compared with white women, black women are more likely to be diagnosed with advanced EC, have more barriers to accessing care and experience increased delays in obtaining an EC diagnosis and commencing treatment. Histological and molecular differences place black women at higher risk of being diagnosed with more aggressive EC subtypes that carry less favourable outcomes. Furthermore, EC diagnostic pathways are less reliable in black women, and black women are less likely to receive evidence-based treatment for EC. This racioethnic disparity in EC outcomes exists both in the UK and US, despite differences in healthcare systems. This review methodically describes the key factors along the patient journey that contribute to the disparity in black women and proposes multifaceted approaches to lessen these gaps