Interglacials of the last 800,000 years

Interglacials, including the present (Holocene) period, are warm, low land ice extent (high sea level), end-members of glacial cycles. Based on a sea level definition, we identify eleven interglacials in the last 800,000 years, a result that is robust to alternative definitions. Data compilations suggest that despite spatial heterogeneity, Marine Isotope Stages (MIS) 5e (last interglacial) and 11c (~400 ka ago) were globally strong (warm), while MIS 13a (~500 ka ago) was cool at many locations. A step change in strength of interglacials at 450 ka is apparent only in atmospheric CO$_{2}$ and in Antarctic and deep ocean temperature. The onset of an interglacial (glacial termination) seems to require a reducing precession parameter (increasing Northern Hemisphere summer insolation), but this condition alone is insufficient. Terminations involve rapid, nonlinear, reactions of ice volume, CO$_{2}$, and temperature to external astronomical forcing. The precise timing of events may be modulated by millennial-scale climate change that can lead to a contrasting timing of maximum interglacial intensity in each hemisphere. A variety of temporal trends is observed, such that maxima in the main records are observed either early or late in different interglacials. The end of an interglacial (glacial inception) is a slower process involving a global sequence of changes. Interglacials have been typically 10–30 ka long. The combination of minimal reduction in northern summer insolation over the next few orbital cycles, owing to low eccentricity, and high atmospheric greenhouse gas concentrations implies that the next glacial inception is many tens of millennia in the future.This paper arose as a result of a succession of workshops of the Past Interglacials Group (PIGS), sponsored by the Past Global Changes Project (PAGES). The authors acknowledge the contributions of all participants at those workshops, of whom the listed authors are only a subset. Numerous funding agencies have contributed to the work of this paper including NSF (USA), NERC and The Royal Society (UK), F.R.S –FNRS (Belgium), and SNF (Switzerland). Most data described in this paper are available through relevant data repositories, http://www.ncdc.noaa.gov/data-access/paleoclimatology-data and www.pangaea.de in particular. In addition, the datasets from which Tables 2 and 3 were derived have been compiled into a spreadsheet as a supplement to this paper. Insolation data for Figure 5 can be calculated using programs available at ftp://ftp.elic.ucl.ac.be/berger/berger78/ and ftp://ftp.elic.ucl.ac.be/berger/ellipticintegrals/.  This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/2015RG00048

Unraveling the forcings controlling the vegetation and climate of the best orbital analogues for the present interglacial in SW Europe

The suitability of MIS 11c and MIS 19c as analogues of our present interglacial and its natural evolution is still debated. Here we examine the regional expression of the Holocene and its orbital analogues over SW Iberia using a model-data comparison approach. Regional tree fraction and climate based on snapshot and transient experiments using the LOVECLIM model are evaluated against the terrestrial-marine profiles from Site U1385 documenting the regional vegetation and climatic changes. The pollen-based reconstructions show a larger forest optimum during the Holocene compared to MIS 11c and MIS 19c, putting into question their analogy in SW Europe. Pollen-based and model results indicate reduced MIS 11c forest cover compared to the Holocene primarily driven by lower winter precipitation, which is critical for Mediterranean forest development. Decreased precipitation was possibly induced by the amplified MIS 11c latitudinal insolation and temperature gradient that shifted the westerlies northwards. In contrast, the reconstructed lower forest optimum at MIS 19c is not reproduced by the simulations probably due to the lack of Eurasian ice sheets and its related feedbacks in the model. Transient experiments with time-varying insolation and CO2 reveal that the SW Iberian forest dynamics over the interglacials are mostly coupled to changes in winter precipitation mainly controlled by precession, CO2 playing a negligible role. Model simulations reproduce the observed persistent vegetation changes at millennial time scales in SW Iberia and the strong forest reductions marking the end of the interglacial "optimum".SFRH/BD/9079/2012, SFRH/BPD/108712/2015, SFRH/BPD/108600/2015info:eu-repo/semantics/publishedVersio

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Heartwater : past, present and future : proceedings of a workshop held at Berg en Dal, Kruger National Park, on 8-16 September 1986

At present, heartwater in the Caribbean is known with certainty only on Guadeloupe, Marie Galante and Antigua; the first 2 islands are widely infected. The most important factors responsible for particular aspects of heartwater in Guadeloupe are: • Cowdria ruminantium of high virulence. • A very resistant cattle population (Creole), not normally clinically affected. • A fairly susceptible goat population (Creole) (22% goats born in endemic areas die after experimental inoculation) which, fortunately, includes breeding lines with inherited resistance characteristics. • Amblyomma variegatum which is present all over the island and all through the year, but with a low infection rate (1-2 % of adult ticks are infected) because of the short period of rickettsemia in infected animals. The low rate of tick infection results in a low endemicity of the disease. For goats, the epidemiologic situation can be regarded as unstable because the low rate of infection in ticks does not allow a natural immunization of the majority of young kids when they still have a non-specific resistance. The possible evolution of heartwater in the Caribbean and in the United States is considered.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.lmchunu2014mn201

Heartwater : past, present and future : proceedings of a workshop held at Berg en Dal, Kruger National Park, on 8-16 September 1986

Experiments were conducted with Creole goats and Amblyomma variegatum ticks in Guadeloupe to investigate whether it is possible to transmit Cowdria ruminantium to susceptible hosts with nymphs fed in the larval stage on recovered goats. Of 88 batches of larvae fed after the return of the goats' temperature to normal, or after challenge or immunosuppression, only the 9 batches of larvae fed during the febrile reaction, 2 batches applied 2 and 3 days respectively after recovery, and a single batch applied 5 days after challence, became infective. On average, blood appears to be infective for A. variegatum larvae for only an 8-day period associated with the temperature reaction following a primary infection. Recovered goats are not reservoirs of Cowdria, even if with one exception in our experiment-they are reinfected after recovery.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.lmchunu2014mn201

Heartwater : past, present and future : proceedings of a workshop held at Berg en Dal, Kruger National Park, on 8-16 September 1986

The resistance rate of different populations of the same breed of creole Guadeloupean goats to Cowdria ruiminatium infection varied greatly depending on the previous heartwater history of each population. After experimental infection of goats removed decades ago from endemic areas, the observed resistance rate was 25 %, while it was 54% in a population that had been isolated from the disease for 10 years and reached 78% in a flock actually exposed to heartwater. This resistance seems to be under genetic control as sex and paternity were the most important factors which could explain resistance in a group of 90 kids of the same flock, tested under controlled conditions. Resistance rate varied greatly (20-83 %) depending on the sire, with a heritability estimate of 0,49 for half sibs and 0,85 for full sibs. A recessive sex-linked gene could be involved in the genetic determination of this resistance. From these observations, it can be stated that in endemic heartwater areas, each population, i.e. each flock, will have developed resistance at a definite rate according to population, age and the extent of past and present exposure to the disease, through a natural selection of resistant lines. Populations removed from exposure to heartwater will progressively lose their ability to resist infection through an increase in the frequency of susceptible stock. If our hypothesis of a recessive sex-linked gene is proved correct, it should be easy to select for improved resistance of the Guadeloupe breed of goat to heartwater.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.lmchunu2014mn201