Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10(-7)). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients

The plankton, aerosol, cloud, ocean ecosystem mission status, science, advances

The Plankton, Aerosol, Cloud, Ocean Ecosystem (PACE) mission represents the National Aeronautics and Space Administration\u27s (NASA) next investment in satellite ocean color and the study of Earth\u27s ocean-atmosphere system, enabling new insights into oceanographic and atmospheric responses to Earth\u27s changing climate. PACE objectives include extending systematic cloud, aerosol, and ocean biological and biogeochemical data records, making essential ocean color measurements to further understand marine carbon cycles, food-web processes, and ecosystem responses to a changing climate, and improving knowledge of how aerosols influence ocean ecosystems and, conversely, how ocean ecosystems and photochemical processes affect the atmosphere. PACE objectives also encompass management of fisheries, large freshwater bodies, and air and water quality and reducing uncertainties in climate and radiative forcing models of the Earth system. PACE observations will provide information on radiative properties of land surfaces and characterization of the vegetation and soils that dominate their reflectance. The primary PACE instrument is a spectrometer that spans the ultraviolet to shortwave-infrared wavelengths, with a ground sample distance of 1 km at nadir. This payload is complemented by two multiangle polarimeters with spectral ranges that span the visible to near-infrared region. Scheduled for launch in late 2022 to early 2023, the PACE observatory will enable significant advances in the study of Earth\u27s biogeochemistry, carbon cycle, clouds, hydrosols, and aerosols in the ocean-atmosphere-land system. Here, we present an overview of the PACE mission, including its developmental history, science objectives, instrument payload, observatory characteristics, and data products

Canta Nación con Nación: una Aproximación Comparativa entre el Son Jarocho y el Joropo Llanero

Dissertação apresentada ao Programa de Pós-Graduação Interdisciplinar em Estudos Latino-Americanos da Universidade Federal da Integração Latino-Americana, como requisito parcialà obtenção do título de Mestra em Estudos Latino-Americanos.El son jarocho de México y el Joropo llanero de Venezuela son dos expresiones musicales que muestran rasgos en común, como resultado de un proceso histórico que los hermana. Ambos tienen su raíz principal en el fandango, celebración músico-bailable que cruzó el océano atlántico de ida y vuelta, formando variadas manifestaciones musicales y danzarías durante la época colonial, tanto en América como en la Península Ibérica. En ese proceso se va conformando también el complejo genérico ternario del Caribe, el cual se subdivide y se expande en las diversas expresiones regionales que aún hoy se conocen. En el Gran Caribe ha habido siempre intercambios musicales, por lo que el flujo de estéticas ha sido permanente y la hermandad dentro del fenómeno fandanguero se viene manifestando en los aspectos musicales como el ritmo, la armonía, lo tímbrico, entre otros. Para destacar las afinidades y diferencias que unen o separan los rasgos identificables se han seleccionado dos ejemplos: el Buscapies (son jarocho) y el Seis Numerao (joropo llanero). Ambos comparten el mismo patrón acordal y son ejemplo de consanguinidad rítmica con acentuaciones específicas. En este sentido, se presentará un análisis musical comparativo de las formas mencionadas, partiendo de la metodología de Simha Ahrom Buscando aproximaciones que se perfilen en los aspectos musicales principalmente

Comparative Effectiveness of Guidelines for the Management of Hyperlipidemia and Hypertension for Type 2 Diabetes Patients

Background: Several guidelines to reduce cardiovascular risk in diabetes patients exist in North America, Europe, and Australia. Their ability to achieve this goal efficiently is unclear. Methods and Findings: Decision analysis was used to compare the efficiency and effectiveness of international contemporary guidelines for the management of hypertension and hyperlipidemia for patients aged 40-80 with type 2 diabetes. Measures of comparative effectiveness included the expected probability of a coronary or stroke event, incremental medication costs per event, and number-needed-to-treat (NNT) to prevent an event. All guidelines are equally effective, but they differ significantly in their medication costs. The range of NNT to prevent an event was small across guidelines (6.5-7.6 for males and 6.5-7.5 for females); a larger range of differences were observed for expected cost per event avoided (ranges, $117,269-$157,186 for males and $115,999-$163,775 for females). Australian and U.S. guidelines result in the highest and lowest expected costs, respectively. Conclusions: International guidelines based on the same evidence and seeking the same goal are similar in their effectiveness; however, there are large differences in expected medication costs. © 2011 Shah et al

Making Connections - Envisioning Springfield\u27s North End

This work explores a service learning strategy in the context of the senior Urban Design Studio taught in the Department of Landscape Architecture and Regional Planning at the University of Massachusetts Amherst. The primary goal of this project is to stimulate a conversation in the neighborhoods of the North End, to develop green design strategies, to improve services and businesses for residents and the employees of local businesses, and to foster cultural engagement and interaction in the North End that will enhance the vibrancy, resilience, and quality of life of this urban community. Making connections - Envisioning Springfield\u27s North End proposes improved connectivity in a physical, cultural, and social sense will be key to attaining these goals and to engaging and synergizing individuals and community groups in the North End - residents, businesses, schools, churches, employers, and employees. Six sustainable learning and planning principles have emerged from this studio: 1. Input and interaction – Visioning workshops connect campus and community 2. Community-building art - Expression of place and people 3. Healthy living - Urban agriculture and education 4. Urban greenways – Abandoned railways and urban rivers and streams 5. Green infrastructure - Green streets as networks and structural framework 6. Sustainable urban form – Mixed use and pedestrian friendly neighborhood

Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages

Distinguishing dendritic cells (DCs) from other cells of the mononuclear phagocyte system is complicated by the shared expression of cell surface markers such as CD11c. In this study, we identified Zbtb46 (BTBD4) as a transcription factor selectively expressed by classical DCs (cDCs) and their committed progenitors but not by plasmacytoid DCs (pDCs), monocytes, macrophages, or other lymphoid or myeloid lineages. Using homologous recombination, we replaced the first coding exon of Zbtb46 with GFP to inactivate the locus while allowing detection of Zbtb46 expression. GFP expression in Zbtb46(gfp/+) mice recapitulated the cDC-specific expression of the native locus, being restricted to cDC precursors (pre-cDCs) and lymphoid organ- and tissue-resident cDCs. GFP(+) pre-cDCs had restricted developmental potential, generating cDCs but not pDCs, monocytes, or macrophages. Outside the immune system, Zbtb46 was expressed in committed erythroid progenitors and endothelial cell populations. Zbtb46 overexpression in bone marrow progenitor cells inhibited granulocyte potential and promoted cDC development, and although cDCs developed in Zbtb46(gfp/gfp) (Zbtb46 deficient) mice, they maintained expression of granulocyte colony-stimulating factor and leukemia inhibitory factor receptors, which are normally down-regulated in cDCs. Thus, Zbtb46 may help enforce cDC identity by restricting responsiveness to non-DC growth factors and may serve as a useful marker to identify rare cDC progenitors and distinguish between cDCs and other mononuclear phagocyte lineages

Novel phase diagram behavior and materials design in heterostructural semiconductor alloys

Structure and composition control the behavior of materials. Isostructural alloying is historically an extremely successful approach for tuning materials properties, but it is often limited by binodal and spinodal decomposition, which correspond to the thermodynamic solubility limit and the stability against composition fluctuations, respectively. We show that heterostructural alloys can exhibit a markedly increased range of metastable alloy compositions between the binodal and spinodal lines, thereby opening up a vast phase space for novel homogeneous single-phase alloys. We distinguish two types of heterostructural alloys, that is, those between commensurate and incommensurate phases. Because of the structural transition around the critical composition, the properties change in a highly nonlinear or even discontinuous fashion, providing a mechanism for materials design that does not exist in conventional isostructural alloys. The novel phase diagram behavior follows from standard alloy models using mixing enthalpies from first-principles calculations. Thin-film deposition demonstrates the viability of the synthesis of these metastable single-phase domains and validates the computationally predicted phase separation mechanism above the upper temperature bound of the nonequilibrium single-phase region