Forty years of paleoecology in the Galapagos

The Galapagos Islands provided one of the first lowland paleoecological records from the Neotropics. Since the first cores were raised from the islands in 1966, there has been a substantial increase in knowledge of past systems, and development of the science of paleoclimatology. The study of fossil pollen, diatoms, corals and compound-specific isotopes on the Galapagos has contributed to the maturation of this discipline. As research has moved from questions about ice-age conditions and mean states of the Holocene to past frequency of El Niño Southern Oscillation, the resolution of fossil records has shifted from millennial to sub-decadal. Understanding the vulnerability of the Galapagos to climate change will be enhanced by knowledge of past climate change and responses in the islands

Experimentation on Analogue Models

Summary Analogue models are actual physical setups used to model something else. They are especially useful when what we wish to investigate is difficult to observe or experiment upon due to size or distance in space or time: for example, if the thing we wish to investigate is too large, too far away, takes place on a time scale that is too long, does not yet exist or has ceased to exist. The range and variety of analogue models is too extensive to attempt a survey. In this article, I describe and discuss several different analogue model experiments, the results of those model experiments, and the basis for constructing them and interpreting their results. Examples of analogue models for surface waves in lakes, for earthquakes and volcanoes in geophysics, and for black holes in general relativity, are described, with a focus on examining the bases for claims that these analogues are appropriate analogues of what they are used to investigate. A table showing three different kinds of bases for reasoning using analogue models is provided. Finally, it is shown how the examples in this article counter three common misconceptions about the use of analogue models in physics

Improved Measurement of the dˉ/uˉ\bar d / \bar u Asymmetry in the Nucleon Sea

Measurements of the ratio of Drell-Yan yields from an 800 \rm{GeV/c} proton beam incident on liquid hydrogen and deuterium targets are reported. Approximately 360,000 Drell-Yan muon pairs remained after all cuts on the data. From these data, the ratio of anti-down ($\bar{d}$) to anti-up ($\bar{u}$) quark distributions in the proton sea is determined over a wide range in Bjorken-$x$. These results confirm previous measurements by E866 and extend them to lower $x$. From these data, $(\bar{d}-\bar{u})$ and $\int(\bar{d}-\bar{u})dx$ are evaluated for $0.015<x<0.35$. These results are compared with parameterizations of various parton distribution functions, models and experimental results from NA51, NMC, and HERMES.Comment: 17 pages, 15 figure

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele