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Anti-Hypertensive Medications and Cardiovascular Events in Older Adults with Multiple Chronic Conditions
Importance
Randomized trials of anti-hypertensive treatment demonstrating reduced risk of cardiovascular events in older adults included participants with less comorbidity than clinical populations. Whether these results generalize to all older adults, most of whom have multiple chronic conditions, is uncertain.
Objective
To determine the association between anti-hypertensive medications and CV events and mortality in a nationally representative population of older adults.
Design
Competing risk analysis with propensity score adjustment and matching in the Medicare Current Beneficiary Survey cohort over three-year follow-up through 2010.
Participants and Setting
4,961 community-living participants with hypertension.
Exposure
Anti-hypertensive medication intensity, based on standardized daily dose for each anti-hypertensive medication class participants used.
Main Outcomes and Measures
Cardiovascular events (myocardial infarction, unstable angina, cardiac revascularization, stroke, and hospitalizations for heart failure) and mortality.
Results
Of 4,961 participants, 14.1% received no anti-hypertensives; 54.6% received moderate, and 31.3% received high, anti-hypertensive intensity. During follow-up, 1,247 participants (25.1%) experienced cardiovascular events; 837 participants (16.9%) died. Of deaths, 430 (51.4%) occurred in participants who experienced cardiovascular events during follow-up. In the propensity score adjusted cohort, after adjusting for propensity score and other covariates, neither moderate (adjusted hazard ratio, 1.08 [95% CI, 0.89–1.32]) nor high (1.16 [0.94–1.43]) anti-hypertensive intensity was associated with experiencing cardiovascular events. The hazard ratio for death among all participants was 0.79 [0.65–0.97] in the moderate, and 0.72 [0.58–0.91] in the high intensity groups compared with those receiving no anti-hypertensives. Among participants who experienced cardiovascular events, the hazard ratio for death was 0.65 [0.48–0.87] and 0.58 [0.42–0.80] in the moderate and high intensity groups, respectively. Results were similar in the propensity score-matched subcohort.
Conclusions and Relevance
In this nationally representative cohort of older adults, anti-hypertensive treatment was associated with reduced mortality but not cardiovascular events. Whether RCT results generalize to older adults with multiple chronic conditions remains uncertain
Targeted capture sequencing in whitebark pine reveals range-wide demographic and adaptive patterns despite challenges of a large, repetitive genome
Whitebark pine (Pinus albicaulis) inhabits an expansive range in western North America, and it is a keystone species of subalpine environments. Whitebark is susceptible to multiple threats – climate change, white pine blister rust, mountain pine beetle, and fire exclusion – and it is suffering significant mortality range-wide, prompting the tree to be listed as ‘globally endangered’ by the International Union for Conservation of Nature and ‘endangered’ by the Canadian government. Conservation collections (in situ and ex situ) are being initiated to preserve the genetic legacy of the species. Reliable, transferrable, and highly variable genetic markers are essential for quantifying the genetic profiles of seed collections relative to natural stands, and ensuring the completeness of conservation collections. We evaluated the use of hybridization-based target capture to enrich specific genomic regions from the 27 GB genome of whitebark pine, and to evaluate genetic variation across loci, trees, and geography. Probes were designed to capture 7,849 distinct genes, and screening was performed on 48 trees. Despite the inclusion of repetitive elements in the probe pool, the resulting dataset provided information on 4,452 genes and 32% of targeted positions (528,873 bp), and we were able to identify 12,390 segregating sites from 47 trees. Variations reveal strong geographic trends in heterozygosity and allelic richness, with trees from the southern Cascade and Sierra Range showing the greatest distinctiveness and differentiation. Our results show that even under non-optimal conditions (low enrichment efficiency; inclusion of repetitive elements in baits), targeted enrichment produces high quality, codominant genotypes from large genomes. The resulting data can be readily integrated into management and gene conservation activities for whitebark pine, and have the potential to be applied to other members of 5-needle pine group (Pinus subsect. Quinquefolia) due to their limited genetic divergence
Climate change, climate justice and the application of probabilistic event attribution to summer heat extremes in the California Central Valley
Probabilistic event attribution (PEA) is an important tool for assessing the contribution of climate change to extreme weather events. Here, PEA is applied to explore the climate attribution of recent extreme heat events in California’s Central Valley. Heat waves have become progressively more severe due to increasing relative humidity and nighttime temperatures, which increases the health risks of exposed communities, especially Latino farmworkers and other socioeconomically disadvantaged communities. Using a superensemble of simulations with the Hadley Centre Regional Model (HadRM3P), we find that (1) simulations of the hottest summer days during the 2000s were twice as likely to occur using observed levels of greenhouse gases than in a counterfactual world without major human activities, suggesting a strong relationship between heat extremes and the increase in human emissions of greenhouse gases, (2) detrimental impacts of heat on public health-relevant variables, such as the number of days above 40 °C, can be quantified and attributed to human activities using PEA, and (3) PEA can serve as a tool for addressing climate justice concerns of populations within developed nations who are disproportionately exposed to climate risks.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Springer. The published article can be found at: http://link.springer.com/journal/1058
Measurement of the forward-backward asymmetries in the production of Ξ and Ω baryons in p p¯ collisions
We measure the forward-backward asymmetries A[subscript]FB of charged Ξ and Ω baryons produced in p (p) over bar collisions recorded by the D0 detector at the Fermilab Tevatron collider at √s = 1.96 TeV as a function of the baryon rapidity y. We find that the asymmetries A[subscript]FB for charged Ξ and Ω baryons are consistent with zero within statistical uncertainties.This is the publisher’s final pdf. The published article is copyrighted by American Physical Society and can be found at: http://journals.aps.org/prd/This is the publisher’s final pdf. The published article is copyrighted by American Physical Society and can be found at: http://journals.aps.org/prd
A Phytophthora sojae effector suppresses endoplasmic reticulum stress-mediated immunity by stabilizing plant Binding immunoglobulin Proteins
Phytophthora pathogens secrete an array of specific effector proteins to manipulate host innate immunity to promote pathogen colonization. However, little is known about the host targets of effectors and the specific mechanisms by which effectors increase susceptibility. Here we report that the soybean pathogen Phytophthora sojae uses an essential effector PsAvh262 to stabilize endoplasmic reticulum (ER)-luminal binding immunoglobulin proteins (BiPs), which act as negative regulators of plant resistance to Phytophthora. By stabilizing BiPs, PsAvh262 suppresses ER stress-triggered cell death and facilitates Phytophthora infection. The direct targeting of ER stress regulators may represent a common mechanism of host manipulation by microbes.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/ncomms/index.htm
Wave-Breaking Turbulence in the Ocean Surface Layer
Observations of winds, waves, and turbulence at the ocean surface are compared with several analytic formulations and a numerical model for the input of turbulent kinetic energy by wave breaking and the subsequent dissipation. The observations are generally consistent with all of the formulations, although some differences are notable at winds greater than 15 m s⁻¹. The depth dependence of the turbulent dissipation rate beneath the waves is fit to a decay scale, which is sensitive to the choice of vertical reference frame. In the surface-following reference frame, the strongest turbulence is isolated within a shallow region of depths much less than one significant wave height. In a fixed reference frame, the strong turbulence penetrates to depths that are at least half of the significant wave height. This occurs because the turbulence of individual breakers persists longer than the dominant period of the waves and thus the strong surface turbulence is carried from crest to trough with the wave orbital motion.This is the publisher’s final pdf. The published article is copyrighted by the American Meteorological Society and can be found at: https://www.ametsoc.org/ams/index.cfm/publications/journals/journal-of-physical-oceanography/The SWIFT wave, wind, and turbulence data are available online (at www.apl.uw.edu/swift) by serial number. The waverider spectra are available as station 166 from the Coastal Data Information Program (CDIP) at the Scripps Institution of Oceanography or the National Data Buoy Center (NDBC) as station 46246.KEYWORDS: Wave breaking, Waves, oceanic, Atmosphere-ocean interaction, Turbulence, Wind waves, Circulation/ Dynamics, Atm/Ocean Structure/ Phenomena, Sea stat
KirkwoodO18TracerMetabolomicsSupportingInformation.zip
The differentiation of precursor cells into mature adipocytes (adipogenesis) has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell line is the most well characterized cellular model of adipogenesis. Using a time course metabolomics approach, we show that the 3T3-L1 preadipocyte metabolome is greatly altered during the first 48 hours of differentiation, where cells go through about two rounds of cell division, a process known as mitotic clonal expansion. Short-chain peptides were among several small molecules that were increased during mitotic clonal expansion. Additional indicators of protein turnover were also increased, including bilirubin, a degradation product of heme-containing proteins, and 3-methylhistidine, a post-translationally modified amino acid that is not reutilized for protein synthesis. To study the origin of the peptides, we treated differentiating preadipocytes with ¹⁸O labeled water and found that ¹⁸O was incorporated into the short chain peptides, confirming them, at least in part, as products of hydrolysis. Inhibitors of the proteasome or matrix metalloproteinases affected the peptide levels during differentiation, but inhibitors of autophagy or peptidases did not. ¹⁸O was also incorporated into several choline metabolites including cytidine 5'-diphosphocholine (CDP-choline), glycerophosphocholine, and several phosphatidylcholine species, indicative of phosphatidylcholine synthesis/degradation and of flux through the CDP-choline cycle, a hallmark of proliferating cells. ¹⁸O-Tracer metabolomics further showed metabolic labeling of glutamate, suggestive of glutaminolysis, also characteristic of proliferating cells. Together, these results highlight the utility of ¹⁸O isotope labeling in combination with metabolomics to uncover changes in cellular metabolism that are not detectable by time-resolved metabolomics
Martínez-CregoRoleofSeagrassTraitsSupportingInfo.zip
Understanding how intra-specific differences in plant traits mediate vulnerability to herbivores of relevant habitat-forming plants is vital to attain a better knowledge on the drivers of the structure and functioning of ecosystems. Such studies, however, are rare in seagrass-mesograzer systems despite the increasingly recognized relevance of mesograzers as seagrass consumers. We investigated the role and potential trade-offs of multiple leaf traits in mediating the vulnerability of the seagrass Zostera noltei to different mesograzer species, the amphipod Gammarus insensibilis and the isopod Idotea chelipes. We worked with plants from two different meadows for which contrasting chemical and structural traits were expected based on previous information. We found that plants with high vulnerability to mesograzers (i.e. those preferred and subjected to higher rates of leaf area loss) had not only higher nitrogen content and lower C:N, fibre, and phenolics, but also tender and thinner leaves. No trade-offs between chemical and structural traits of the seagrass were detected, as they were positively correlated. When leaf physical structure was removed using agar-reconstituted food, amphipod preference towards high-susceptibility plants disappeared; thus indicating that structural rather than chemical traits mediated the feeding preference. Removal of plant structure reduced the size of isopod preference to less than half, indicating a stronger contribution of structural traits (> 50%) but combined with chemical/nutritional traits in mediating the preference. We then hypothesized that the high environmental nutrient levels recorded in the meadow exhibiting high susceptibility modulate the differences observed between meadows in seagrass traits. To test this hypothesis, we exposed low-vulnerability shoots to eutrophic nutrient levels in a 6-week enrichment experiment. Nutrient enrichment increased Z. noltei nitrogen content and lowered C:N, fibre, and phenolics, but had no effect on structural traits. Overall, our findings help to better understand the trait-mediated seagrass susceptibility to mesograzers and reinforce the increasingly recognized role of structural defences against herbivory
Behavioral Thresholds in Mixtures of Sand and Kaolinite Clay
Nearly all soils are comprised of mixtures of coarse and fine particles. Behavior under mechanical and thermal loading of soil is strongly influenced, and in some cases governed, by the ratio of coarse to fine particles. A better understanding of the fundamental behavior of soil mixtures will provide insight to design decisions for new and emerging geotechnologies. In this work, behavioral threshold fines fractions were identified by experimental methods, where the threshold was defined as the point where changes in the coarse/fine mixture ratio result in abrupt behavior changes. Binary mixtures of sand and kaolinite clay ranging from 0 to 100% fines content were subjected to consistency and undrained shear strength testing with the fall-cone apparatus, compressibility tests using an oedometric cell, thermal conductivity tests with a thermal needle probe, and stress-strain-strength testing in undrained triaxial shear. Results indicate that behavioral thresholds exist at a critical fines content where a minimum void ratio occurs and at a percolation threshold where continuous force chains are present. The behavior changes are explained using theories of effective properties and percolation. Interpretations of these results lead to a clearer understanding of soil behavior
Implementing the Optimal Provision of Ecosystem Services
Many ecosystem services are public goods whose provision depends on the spatial pattern of land use. The pattern of land use is often determined by the decisions of multiple private landowners. Increasing the provision of ecosystem services, while beneficial for society as a whole, may be costly to private landowners. A regulator interested in providing incentives to landowners for increased provision of ecosystem services often lacks complete information on landowners’ costs. The combination of spatially-dependent benefits and asymmetric cost information means that the optimal provision of ecosystem services cannot be achieved using standard regulatory or payment for ecosystem services (PES) approaches. Here we show that an auction that sets payments between landowners and the regulator for the increased value of ecosystem services with conservation provides incentives for landowners to truthfully reveal cost information, and allows the regulator to implement the optimal provision of ecosystem services, even in the case with spatially-dependent benefits and asymmetric information