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Though primarily driven by insolation changes associated with well-known variations in Earth's astronomical parameters, the response of the climate system during interglacials includes a diversity of feedbacks involving the atmosphere, ocean, sea ice, vegetation and land ice. A thorough multi-model-data comparison is essential to assess the ability of climate models to resolve interglacial temperature trends and to help in understanding the recorded climatic signal and the underlying climate dynamics. We present the first multi-model-data comparison of transient millennial-scale temperature changes through two intervals of the Present Interglacial (PIG; 8-1.2 ka) and the Last Interglacial (LIG; 123-116.2 ka) periods. We include temperature trends simulated by 9 different climate models, alkenone-based temperature reconstructions from 117 globally distributed locations (about 45% of them within the LIG) and 12 ice-core-based temperature trends from Greenland and Antarctica (50% of them within the LIG). The definitions of these specific interglacial intervals enable a consistent inter-comparison of the two intervals because both are characterised by minor changes in atmospheric greenhouse gas concentrations and more importantly by insolation trends that show clear similarities. Our analysis shows that in general the reconstructed PIG and LIG Northern Hemisphere mid-to-high latitude cooling compares well with multi-model, mean-temperature trends for the warmest months and that these cooling trends reflect a linear response to the warmest-month insolation decrease over the interglacial intervals. The most notable exception is the strong LIG cooling trend reconstructed from Greenland ice cores that is not simulated by any of the models. A striking model-data mismatch is found for both the PIG and the LIG over large parts of the mid-to-high latitudes of the Southern Hemisphere where the data depicts negative temperature trends that are not in agreement with near zero tren

Subtropical and extratropical proxy records of wind field, sea level pressure (SLP), temperature and hydrological anomalies from South Africa, Australia/New Zealand, Patagonian South America and Antarctica were used to reconstruct the Indo-Pacific extratropical southern hemisphere sea-level pressure anomaly (SLPa) fields for the Medieval Climate Anomaly (MCA ~700–1350 CE) and transition to the Little Ice Age (LIA 1350–1450 CE). The multivariate array of proxy data were simultaneously evaluated against global climate model output in order to identify climate state analogues that are most consistent with the majority of proxy data. The mean SLP and SLP anomaly patterns derived from these analogues illustrate the evolution of low frequency changes in the extratropics. The Indo-Pacific extratropical mean climate state was dominated by a strong tropical interaction with Antarctica emanating from: (1) the eastern Indian and south-west Pacific regions prior to 1100 CE, then, (2) the eastern Pacific evolving to the central Pacific La Niña-like pattern interacting with a +ve SAM to 1300 CE. A relatively abrupt shift to –ve SAM and the central Pacific El Niño-like pattern occurred at ~1300. A poleward (equatorward) shift in the subtropical ridge occurred during the MCA (MCA–LIA transition). The Hadley Cell expansion in the Australian and Southwest Pacific, region together with the poleward shift of the zonal westerlies is contemporaneous with previously reported Hadley Cell expansion in the North Pacific and Atlantic regions, and suggests that bipolar climate symmetry was a feature of the MCA.

© Author(s) 2013. LFD was funded by a FPU grant: AP2009-4061. LFD and JFGR acknowledge project grants UCM-921407, CGL2008-06558-C02-02/CLI, CGL2011-29672-C02-02, 200800050083542 and 200800050084028. CCR acknowledges SNF-FUPSOL. DB acknowledges projects CGL2008-05968-C02-01 and ENAC-PTDC/AAC-CLI/103567/2008. JL acknowledges EU/FP7-ACQWA-NO212250, DFG-PRIME1,2, LU1608/1-1/AOBJ:568460 and LU1608/2-1/AOBJ:575150. JS, DS and PY acknowledge the ANR ESCARSEL grant., Understanding natural climate variability and its driving factors is crucial to assessing future climate change. Therefore, comparing proxy-based climate reconstructions with forcing factors as well as comparing these with paleo-climate model simulations is key to gaining insights into the relative roles of internal versus forced variability. A review of the state of modelling of the climate of the last millennium prior to the CMIP5-PMIP3 (Coupled Model Intercomparison Project Phase 5-Paleoclimate Modelling Intercomparison Project Phase 3) coordinated effort is presented and compared to the available temperature reconstructions. Simulations and reconstructions broadly agree on reproducing the major temperature changes and suggest an overall linear response to external forcing on multidecadal or longer timescales. Internal variability is found to have an important influence at hemispheric and global scales. The spatial distribution of simulated temperature changes during the transition from the Medieval Climate Anomaly to the Little Ice Age disagrees with that found in the reconstructions. Thus, either internal variability is a possible major player in shaping temperature changes through the millennium or the model simulations have problems realistically representing the response pattern to external forcing. A last millennium transient climate response (LMTCR) is defined to provide a quantitative framework for analysing the consistency between simulated and reconstructed climate. Beyond an overall agreement between simulated and reconstructed LMTCR ranges, this analysis is able to single out specific discrepancies between some reconstructions and the ensemble of simulations. The disagreement is found in the cases where the reconstructions show reduced covariability with external forcings or when they present high rates of temperature change., FPU, SNF-FUPSOL, ANR ESCARSEL, Depto. de Física de la Tierra y Astrofísica, Fac. de Ciencias Físicas, TRUE, pub

There is an overwhelming body of evidence to support the existence of higher brain circuitries involved in the sensory detection of airways irritation and the motor control of coughing. The concept that cough is purely a reflex response to airways irritation is now superseded by the recognition that perception of an urge-to-cough and altered behavioral modification of coughing are key elements of cough disorders associated with airways disease. Understanding the pathways by which airway sensory nerves ascend into the brain and the patterns of neural activation associated with airways irritation will undoubtedly provide new insights into disordered coughing. This brief review aims to explore our current understanding of higher order cough networks by summarizing data from recent neuroanatomical and functional studies in animals and humans. We provide evidence for the existence of distinct higher order network components involved in the discrimination of signals arising from the airways and the motor control of coughing. The identification of these network components provides a blueprint for future research and the development of targeted managements for cough and the urge-to-cough.

The last interglaciation (~130 to 116 ka) is a time period with a strong astronomically induced seasonal forcing of insolation compared to the present. Proxy records indicate a significantly different climate to that of the modern, in particular Arctic summer warming and higher eustatic sea level. Because the forcings are relatively well constrained, it provides an opportunity to test numerical models which are used for future climate prediction. In this paper we compile a set of climate model simulations of the early last interglaciation (130 to 125 ka), encompassing a range of model complexities. We compare the simulations to each other and to a recently published compilation of last interglacial temperature estimates. We show that the annual mean response of the models is rather small, with no clear signal in many regions. However, the seasonal response is more robust, and there is significant agreement amongst models as to the regions of warming vs cooling. However, the quantitative agreement of the model simulations with data is poor, with the models in general underestimating the magnitude of response seen in the proxies. Taking possible seasonal biases in the proxies into account improves the agreement, but only marginally. However, a lack of uncertainty estimates in the data does not allow us to draw firm conclusions. Instead, this paper points to several ways in which both modelling and data could be improved, to allow a more robust model–data comparison.

Earth’s interannual climate variability is dominated by El Niño/Southern Oscillation (ENSO). Palaeoclimate records indicate a lower ENSO variance during the middle Holocene compared with today1, 2, 3, 4, 5, 6; however, model simulations have not reproduced the full magnitude of the changes7, 8, 9, 10, and whether external forcing drives large intrinsic ENSO variability11 is therefore a matter of considerable debate. Here we present a 175-year-long, monthly resolved oxygen isotope record, obtained from a Porites coral microatoll located on Kiritimati (Christmas) Island, in the NINO3.4 region of the central equatorial Pacific. Our quantitative record of ENSO variability about 4,300 years ago shows that ENSO variance was persistently reduced by 79%, compared with today, and it exhibits a dominant annual cycle. Season-specific analysis shows that El Niño events were damped during their September–November growth phase, and delayed relative to the climatological year. We suggest that the higher boreal summer insolation at the time strengthened the tropical Pacific zonal winds as well as the gradients in sea surface temperature, and thereby led to an enhanced annual cycle and suppressed ENSO. As the weak ENSO is subject to interdecadal amplitude modulation, we conclude that amplitude modulation is likely to remain robust under altered climates. Our findings show that ENSO is capable of responding to external forcing.

Item does not contain fulltext, PURPOSE: Perceiving favourable changes from one's illness may go hand in hand with experiencing harmful psychosocial effects. Each of these constructs should be considered when examining children's levels of psychological adjustment following stressful life events. A paediatric instrument that accounts for both positive and negative impact of stressful events has not been investigated in The Netherlands before. The aim of the study was to investigate psychometric properties of the Dutch version of the Benefit and Burden Scale for Children (BBSC), a 20-item questionnaire that intends to measure potential benefit and burden of illness in children. METHODS: Dutch paediatric survivors of childhood cancer aged 8-18 (N = 77) completed the BBSC and other psychological questionnaires: Pediatric Quality of Life Inventory (health-related quality of life), State-Trait Anxiety Inventory for Children (anxiety), Children's Revised Impact of Event Scale (posttraumatic stress) and Strengths and Difficulties Questionnaire (behavioural functioning). Reliability and validity were evaluated. RESULTS: Internal consistency (Cronbach's alpha, benefit 0.84, burden 0.72), test-retest reliability (benefit r = 0.74, burden r = 0.78) and homogeneity (mean inter-item correlation, benefit r = 0.34, burden r = 0.22) were satisfactory. Burden was associated with HRQoL (-), anxiety (+), posttraumatic stress symptoms (+) and behavioural problems. Benefit did not correlate with the psychological outcomes. CONCLUSIONS: The Dutch version of the BBSC shows promising psychometric properties. Perceived benefit and disease-related burden are distinct constructs; both should be considered when examining children's psychological adjustment to potentially traumatic experiences. The BBSC may be useful as monitoring and screening instrument.

Human TLR7 and 8 (hTLR7/8) have been implicated in the sequence-dependent detection of RNA oligonucleotides in immune cells. Although hTLR7 sequence-specific sensing of short RNAs has been inferred from studies of murine TLR7, this has yet to be established for hTLR7. We found that different short ssRNA sequences selectively induced either TNF-alpha or IFN-alpha in human PBMCs. The sequence-specific TNF-alpha response to ssRNAs observed in PBMCs could be replicated in activated human macrophage-like (THP-1) cells pretreated with IFN-gamma. Surprisingly, suppression of hTLR7 expression by RNA interference in this model reduced sensing of all immunostimulatory ssRNAs tested. Modulation of the relative expression ratio of hTLR7 to hTLR8 in THP-1 cells correlated with differential sensing of immunostimulatory sequences. Furthermore, the sequence-specific IFN-alpha induction profile in human PBMCs was accurately modeled by a sequence-specific activation of murine TLR7 in mouse macrophages. Thus, we demonstrate for the first time that hTLR7 is involved in sequence-specific sensing of ssRNAs. We establish a novel cell model for the prediction of TNF-alpha induction by short RNAs in human macrophages. Our results suggest that differential sequence-specific sensing of RNA oligonucleotides between human and mouse macrophages is due to the modulation of TLR7 sensing by human TLR8. Copyright © 2008 by The American Association of Immunologists, Inc.