Inter-model variability and biases of the global water cycle in CMIP3 coupled climate models

Observed changes such as increasing global temperatures and the intensification of the global water cycle in the 20th century are robust results of coupled general circulation models (CGCMs). In spite of these successes, model-to-model variability and biases that are small in first order climate responses, however, have considerable implications for climate predictability especially when multi-model means are used. We show that most climate simulations of the 20th and 21st century A2 scenario performed with CMIP3 (Coupled Model Inter-comparison Project Phase 3) models have deficiencies in simulating the global atmospheric moisture balance. Large biases of only a few models (some biases reach the simulated global precipitation changes in the 20th and 21st centuries) affect the multi-model mean global moisture budget. An imbalanced flux of -0.14 Sv exists while the multi-model median imbalance is only -0.02 Sv. Moreover, for most models the detected imbalance changes over time. As a consequence, in 13 of the 18 CMIP3 models examined, global annual mean precipitation exceeds global evaporation, indicating that there should be a 'leaking' of moisture from the atmosphere whereas for the remaining five models a 'flooding' is implied. Nonetheless, in all models, the actual atmospheric moisture content and its variability correctly increases during the course of the 20th and 21st centuries. These discrepancies therefore imply an unphysical and hence 'ghost' sink/source of atmospheric moisture in the models whose atmospheres flood/leak. The ghost source/sink of moisture can also be regarded as atmospheric latent heating/cooling and hence as positive/negative perturbation of the atmospheric energy budget or non-radiative forcing in the range of -1 to +6 W m^-2 (median +0.1 W m^-2). The inter-model variability of the global atmospheric moisture transport from oceans to land areas, which impacts the terrestrial water cycle, is also quite high and ranges from 0.26 to 1.78 Sv. In the 21st century this transport to land increases by about 5% per century with a model-to-model range from 1 to 13%. We suggest that this variability is weakly correlated to the land-sea contrast in air temperature change of these models. Spatially heterogeneous forcings such as aerosols contribute to the variability in moisture transport, at least in one model. The polewards shifts of dry zones in climate simulations of the 21st century are also assessed. It is shown that the multi-model means of the two subsets of models with negative and positive imbalances in the atmospheric moisture budget produce spatial variability in the dry zone positions similar in size to the spatial shifts expected from 21st century global warming. Thus, the selection of models also affects the multi-model mean dry zone extension. In general, we caution the use of multi-model means of E - P fields and suggest self-consistency tests for climate models

The Vertical Distribution of Climate Forcings and Feedbacks from the Surface to Top of Atmosphere

The radiative forcings and feedbacks that determine Earth’s climate sensitivity are typically defined at the top-of-atmosphere (TOA) or tropopause, yet climate sensitivity itself refers to a change in temperature at the surface. In this paper, we describe how TOA radiative perturbations translate into surface temperature changes. It is shown using first principles that radiation changes at the TOA can be equated with the change in energy stored by the oceans and land surface. This ocean and land heat uptake in turn involves an adjustment of the surface radiative and non-radiative energy fluxes, with the latter being comprised of the turbulent exchange of latent and sensible heat between the surface and atmosphere. We employ the radiative kernel technique to decompose TOA radiative feedbacks in the IPCC Fourth Assessment Report climate models into components associated with changes in radiative heating of the atmosphere and of the surface. (We consider the equilibrium response of atmosphere-mixed layer ocean models subjected to an instantaneous doubling of atmospheric CO2). It is shown that most feedbacks, i.e., the temperature, water vapor and cloud feedbacks, (as well as CO2 forcing) affect primarily the turbulent energy exchange at the surface rather than the radiative energy exchange. Specifically, the temperature feedback increases the surface turbulent (radiative) energy loss by 2.87 W m−2 K−1 (0.60 W m−2 K−1) in the multimodel mean; the water vapor feedback decreases the surface turbulent energy loss by 1.07 W m−2 K−1 and increases the surface radiative heating by 0.89 W m−2 K−1; and the cloud feedback decreases both the turbulent energy loss and the radiative heating at the surface by 0.43 and 0.24 W m−2 K−1, respectively. Since changes to the surface turbulent energy exchange are dominated in the global mean sense by changes in surface evaporation, these results serve to highlight the fundamental importance of the global water cycle to Earth’s climate sensitivity

Diabetic Mouse Model of Orthopaedic Implant-Related Staphylococcus Aureus Infection

BACKGROUND: Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals. METHODOLOGY: A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1 7103 colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count), histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy). RESULTS: Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant. CONCLUSIONS: Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals

The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE:The study protocol

Background: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods: IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients' demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions: IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease's awareness

PDRMIP: a precipitation driver and response model intercomparison project - protocol and preliminary results

PDRMIP investigates the role of various drivers of climate change for mean and extreme precipitation changes, based on multiple climate model output and energy budget analyses. As the global temperature increases with changing climate, precipitation rates and patterns are affected through a wide range of physical mechanisms. The globally averaged intensity of extreme precipitation also changes more rapidly than the globally averaged precipitation rate. While some aspects of the regional variation in precipitation predicted by climate models appear robust, there is still a large degree of inter-model differences unaccounted for. Individual drivers of climate change initially alter the energy budget of the atmosphere leading to distinct rapid adjustments involving changes in precipitation. Differences in how these rapid adjustment processes manifest themselves within models are likely to explain a large fraction of the present model spread and needs better quantifications to improve precipitation predictions. Here, we introduce the Precipitation Driver and Response Model Intercomparison Project (PDRMIP), where a set of idealized experiments designed to understand the role of different climate forcing mechanisms were performed by a large set of climate models. PDRMIP focuses on understanding how precipitation changes relating to rapid adjustments and slower responses to climate forcings are represented across models. Initial results show that rapid adjustments account for large regional differences in hydrological sensitivity across multiple drivers. The PDRMIP results are expected to dramatically improve our understanding of the causes of the present diversity in future climate projections

A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate

Background: Owing to its role in cancer, the phosphoinositide 3-kinase (PI3K)/Akt pathway is an attractive target for therapeutic intervention. We previously reported that the inhibition of Akt by inositol 1,3,4,5,6- pentakisphosphate (InsP5) results in anti-tumour properties. To further develop this compound we modified its structure to obtain more potent inhibitors of the PI3K/Akt pathway.Methods: Cell proliferation/survival was determined by cell counting, sulphorhodamine or acridine orange/ethidium bromide assay; Akt activation was determined by western blot analysis. In vivo effect of compounds was tested on PC3 xenografts, whereas in vitro activity on kinases was determined by SelectScreen Kinase Profiling Service.Results: The derivative 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5) is active towards cancer types resistant to InsP5 in vitro and in vivo. 2-O-Bn-InsP5 possesses higher pro-apoptotic activity than InsP 5 in sensitive cells and enhances the effect of anti-cancer compounds. 2-O-Bn-InsP5 specifically inhibits 3-phosphoinositide- dependent protein kinase 1 (PDK1) in vitro (IC 50 in the low nanomolar range) and the PDK1-dependent phosphorylation of Akt in cell lines and excised tumours. It is interesting to note that 2-O-Bn-InsP5 also inhibits the mammalian target of rapamycin (mTOR) in vitro.Conclusions: InsP5 and 2-O-Bn-InsP5 may represent lead compounds to develop novel inhibitors of the PI3K/Akt pathway (including potential dual PDK1/mTOR inhibitors) and novel potential anti-cancer drugs