Carbon dioxide and climate impulse response functions for the computation of greenhouse gas metrics: a multi-model analysis

The responses of carbon dioxide (CO2) and other climate variables to an emission pulse of CO2 into the atmosphere are often used to compute the Global Warming Potential (GWP) and Global Temperature change Potential (GTP), to characterize the response timescales of Earth System models, and to build reduced-form models. In this carbon cycle-climate model intercomparison project, which spans the full model hierarchy, we quantify responses to emission pulses of different magnitudes injected under different conditions. The CO2 response shows the known rapid decline in the first few decades followed by a millennium-scale tail. For a 100 Gt-C emission pulse added to a constant CO2 concentration of 389 ppm, 25 ± 9% is still found in the atmosphere after 1000 yr; the ocean has absorbed 59 ± 12% and the land the remainder (16 ± 14%). The response in global mean surface air temperature is an increase by 0.20 ± 0.12 °C within the first twenty years; thereafter and until year 1000, temperature decreases only slightly, whereas ocean heat content and sea level continue to rise. Our best estimate for the Absolute Global Warming Potential, given by the time-integrated response in CO2 at year 100 multiplied by its radiative efficiency, is 92.5 × 10−15 yr W m−2 per kg-CO2. This value very likely (5 to 95% confidence) lies within the range of (68 to 117) × 10−15 yr W m−2 per kg-CO2. Estimates for time-integrated response in CO2 published in the IPCC First, Second, and Fourth Assessment and our multi-model best estimate all agree within 15% during the first 100 yr. The integrated CO2 response, normalized by the pulse size, is lower for pre-industrial conditions, compared to present day, and lower for smaller pulses than larger pulses. In contrast, the response in temperature, sea level and ocean heat content is less sensitive to these choices. Although, choices in pulse size, background concentration, and model lead to uncertainties, the most important and subjective choice to determine AGWP of CO2 and GWP is the time horizon.

Asking Sensitive Questions in Online Surveys: An Experimental Comparison of the Randomized Response Technique and the Crosswise Model

Self-administered online surveys provide a higher level of privacy protection to respondents than surveys administered by an interviewer. Yet, studies show that asking sensitive questions is problematic also in self-administered mode. Because respondents might not be willing to reveal the truth and provide answers that are subject to social desirability bias, the validity of prevalence estimates of sensitive behaviors gained via online surveys can be challenged. A well-known method to combat these problems is the Randomized Response Technique (RRT). However, convincing evidence that the RRT provides more valid estimates than direct questioning in online mode is still lacking. Moreover, an alternative approach called the Crosswise Model (CM) has recently been suggested to overcome some of the deficiencies of the RRT. In the context of an online survey on plagiarism and cheating on exams among students of two Swiss universities (N = 6,494), we tested different implementations of the RRT and the CM and compared them to direct questioning using a randomized experimental design. Results reveal a poor performance of the RRT, which failed to elicit higher prevalence estimates than direct questioning. Using the CM however, significantly higher prevalence estimates were obtained making it a promising new alternative to the conventional RRT.

Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins.

cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture.

Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment.

Sensitive Questions in Online Surveys: An Experimental Evaluation of the Randomized Response Technique and the Crosswise Model

Self-administered online surveys provide a higher level of privacy protection to respondents than surveys administered by an interviewer. Yet, studies indicate that asking sensitive questions is problematic also in self-administered surveys. Because respondents might not be willing to reveal the truth and provide answers that are subject to social desirability bias, the validity of prevalence estimates of sensitive behaviors from online surveys can be challenged. A well-known method to overcome these problems is the Randomized Response Technique (RRT). However, convincing evidence that the RRT provides more valid estimates than direct questioning in online surveys is still lacking. A new variant of the RRT called the Crosswise Model has recently been proposed to overcome some of the deficiencies of existing RRT designs. We therefore conducted an experimental study in which different implementations of the RRT, including two implementations of the crosswise model, were tested and compared to direct questioning. Our study is a large-scale online survey (N = 6,037) on sensitive behaviors by students such as cheating in exams and plagiarism. Results indicate that the crosswise-model RRT---unlike the other variants of RRT we evaluated---yields higher prevalence estimates of sensitive behaviors than direct questioning. Whether higher estimates are a sufficient condition for more valid results, however, remains questionable.

Immune-Deficient Drosophila melanogaster: A Model for the Innate Immune Response to Human Fungal Pathogens

We explored the host-pathogen interactions of the human opportunistic fungus Candida albicans using Drosophila melanogaster. We established that a Drosophila strain devoid of functional Toll receptor is highly susceptible to the human pathogen C. albicans. Using this sensitive strain, we have been able to show that a set of specific C. albicans mutants of different virulence in mammalian infection models are also impaired in virulence in Drosophila and remarkably display the same rank order of virulence. This immunodeficient insect model also revealed virulence properties undetected in an immunocompetent murine model of infection. The genetic systems available in both host and pathogen will enable the identification of host-specific components and C. albicans genes involved in the host-fungal interplay.

Thermal processing of bone: in vitro response of mesenchymal cells to bone-conditioned medium

The autoclaving, pasteurization, and freezing of bone grafts to remove bacteria and viruses, and for preservation, respectively, is considered to alter biological properties during graft consolidation. Fresh bone grafts release paracrine-like signals that are considered to support tissue regeneration. However, the impact of the autoclaving, pasteurization, and freezing of bone grafts on paracrine signals remains unknown. Therefore, conditioned medium was prepared from porcine cortical bone chips that had undergone thermal processing. The biological properties of the bone-conditioned medium were assessed by examining the changes in expression of target genes in oral fibroblasts. The data showed that conditioned medium obtained from bone chips that had undergone pasteurization and freezing changed the expression of adrenomedullin, pentraxin 3, BTB/POZ domain-containing protein 11, interleukin 11, NADPH oxidase 4, and proteoglycan 4 by at least five-fold in oral fibroblasts. Bone-conditioned medium obtained from autoclaved bone chips, however, failed to change the expression of the respective genes. Also, when bone-conditioned medium was prepared from fresh bone chips, autoclaving blocked the capacity of bone-conditioned medium to modulate gene expression. These in vitro results suggest that pasteurization and freezing of bone grafts preserve the release of biologically active paracrine signals, but autoclaving does not. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. KEYWORDS: allogeneic bone; augmentation; autoclaving; autologous bone; bone bank; bone grafts; bone regeneration; bone supernatant; bone-conditioned medium; freezing; pasteurization

In vivo degradation of magnesium plate/screw osteosynthesis implant systems: Soft and hard tissue response in a calvarial model in miniature pigs.

Biodegradable magnesium plate/screw osteosynthesis systems were implanted on the frontal bone of adult miniature pigs. The chosen implant geometries were based on existing titanium systems used for the treatment of facial fractures. The aim of this study was to evaluate the in vivo degradation and tissue response of the magnesium alloy WE43 with and without a plasma electrolytic surface coating. Of 14 animals, 6 received magnesium implants with surface modification (coated), 6 without surface modification (uncoated), and 2 titanium implants. Radiological examination of the skull was performed at 1, 4, and 8 weeks post-implantation. After euthanasia at 12 and 24 weeks, X-ray, computed tomography, and microfocus computed tomography analyses and histological and histomorphological examinations of the bone/implant blocks were performed. The results showed a good tolerance of the plate/screw system without wound healing disturbance. In the radiological examination, gas pocket formation was found mainly around the uncoated plates 4 weeks after surgery. The micro-CT and histological analyses showed significantly lower corrosion rates and increased bone density and bone implant contact area around the coated screws compared to the uncoated screws at both endpoints. This study shows promising results for the further development of coated magnesium implants for the osteosynthesis of the facial skeleton.

Analysis of the Heat-Shock Response Displayed by Two Chaetomium Species Originating from Different Thermal Environments

Three features of the heat shock response, reorganization of protein expression, intracellular accumulation of trehalose, and alteration in unsaturation degree of fatty acids were investigated in the thermophilic fungus Chaetomium thermophile and compared to the response displayed by a closely related mesophilic species, C. brasiliense. Thermophilic heat shock response paralleled the mesophilic response in many respects like (i) the temperature difference observed between normothermia and the upper limit of translational activity, (ii) the transient nature of the heat shock response at the level of protein expression including both the induction of heat shock proteins (HSPs) as well as the repression of housekeeping proteins, (iii) the presence of representatives of high-molecular-weight {HSPs} families, (iv) intracellular accumulation of trehalose, and finally (v) modifications in fatty acid composition. On the other hand, a great variability between the two organisms was observed for the proteins expressed during stress, in particular a protein of the {HSP60} family that was only observed in C. thermophile. This peptide was also present constitutively at normal temperature and may thus fulfil thermophilic functions. It is shown that accumulation of trehalose does not play a part in thermophily but is only a stress response. C. thermophile contains less polyunsaturated fatty acids at normal temperature than C. brasiliense, a fact that can be directly related to thermophily. When subjected to heat stress, both organisms tended to accumulate shorter and less unsaturated fatty acids.

Roadmap for implementing the Chronic Care Model for weight management: Healthcare Institution's Response to Obesity (HIRO)

Background. Excess weight and obesity are at epidemic proportions in the United States and place individuals at increased risk for a variety of chronic conditions. Rates of diabetes, high blood pressure, coronary artery disease, stroke, cancer, and arthritis are all influenced by the presence of obesity. Small reductions in excess weight can produce significant positive clinical outcomes. Healthcare organizations have a vital role to play in the identification and management of obesity. Currently, healthcare providers do not adequately diagnose and manage excess weight in patients. Lack of skill, time, and knowledge are commonly cited as reasons for non-adherence to recommended standards of care. The Chronic Care Model offers an approach to healthcare organizations for chronic disease management. The model consists of six elements that work together to empower both providers and patients to have more productive interactions: the community, the health system itself, self-management support, delivery system design, decision support, and clinical information systems. The model and its elements may offer a framework through which healthcare organizations can adapt to support, educate, and empower providers and patients in the management of excess weight and obesity. Successful management of excess weight will reduce morbidity and mortality of many chronic conditions. Purpose. The purpose of this review is to synthesize existing research on the effectiveness of the Chronic Care Model and its elements as they relate to weight management and behaviors associated with maintaining a healthy weight. Methods: A narrative review of the literature between November 1998 and November 2008 was conducted. The review focused on clinical trials, systematic reviews, and reports related to the chronic care model or its elements and weight management, physical activity, nutrition, or diabetes. Fifty-nine articles are included in the review. Results. This review highlights the use of the Chronic Care Model and its elements that can result in improved quality of care and clinical outcomes related to weight management, physical activity, nutrition, and diabetes. Conclusions. Healthcare organizations can use the Chronic Care Model framework to implement changes within their systems to successfully address overweight and obesity in their patient populations. Specific recommendations for operationalizing the Chronic Care Model elements for weight management are presented.^

Disease risk factors and humoral antibody response to periodontal-associated pathogens: A model to evaluate periodontal disease in older adults

Periodontal diseases (PD) are infectious, inflammatory, and tissue destructive events which affect the periodontal ligament that surround and support the teeth. Periodontal diseases are the major cause of tooth loss after age 35, with gingivitis and periodontitis affecting 75% of the adult population. A select group of bacterial organisms are associated with periodontal pathogenesis. There is a direct association between oral hygiene and prevention of PD. The importance of genetic differences and host immune response capabilities in determining host, susceptibility or resistance to PD has not been established. This study examined the risk factors and serum (humoral) immune response to periodontal diseased-associated pathogens in a 55 to 80+ year old South Texas study sample with PD. This study sample was described by: age, sex, ethnicity, the socioeconomic factors marital status, income and occupation, IgG, IgA, IgM immunoglobulin status, and the autoimmune response markers rheumatoid factor (RF) and antinuclear antibody (ANA). These variables were used to determine the risk factors associated with development of PD. Serum IgG, IgA, IgM antibodies to bacterial antigens provided evidence for disease exposure.^ A causal model for PD was constructed from associations for risk factors (ethnicity, marital status, income, and occupation) with dental exam and periodontitis. The multiple correlation between PD and ethnicity, income and dental exam was significant. Hispanics of low income were least likely to have had a dental exam in the last year and most likely to have PD. The etiologic agents for PD, as evidenced by elevated humoral antibody responses, were the Gram negative microorganisms Bacteroides gingivalis, serotypes FDC381 and SUNYaBA7A1-28, and Wolinella recta. Recommendation for a PD prevention and control program are provided. ^

RESPIRATORY COMPENSATION MECHANISMS IN THE UPPER AND LOWER RESPIRATORY TRACTS OF AN ANIMAL MODEL AFTER SUBCHRONIC INHALATION EXPOSURE TO FORMALDEHYDE: IMPLICATIONS FOR TOXICOLOGY RISK ASSESSMENT (DEPOSITION, DOSE RECEIVED, RESPONSE)

The potential for significant human populations to experience long-term inhalation of formaldehyde and reports of symptomatology due to this exposure has led to a considerable interest in the toxicologic assessment of risk from subchronic formaldehyde exposures using animal models. Since formaldehyde inhalation depresses certain respiratory parameters in addition to its other forms of toxicity, there is a potential for the alteration of the actual dose received by the exposed individual (and the resulting toxicity) due to this respiratory effect. The respiratory responses to formaldehyde inhalation and the subsequent pattern of deposition were therefore investigated in animals that had received subchronic exposure to the compound, and the potential for changes in the formaldehyde dose received due to long-term inhalation evaluated. Male Sprague-Dawley rats were exposed to either 0, 0.5, 3, or 15 ppm formaldehyde for 6 hours/day, 5 days/week for up to 6 months. The patterns of respiratory response, deposition and the compensation mechanisms involved were then determined in a series of formaldehyde test challenges to both the upper and to the lower respiratory tracts in separate groups of subchronically exposed animals and age-specific controls (four concentration groups, two time points). In both the control and pre-exposed animals, there was a characteristic recovery of respiratory parameters initially depressed by formaldehyde inhalation to at or approaching pre-exposure levels within 10 minutes of the initiation of exposure. Also, formaldehyde deposition was found to remain very high in the upper and lower tracts after long-term exposure. Therefore, there was probably little subsequent effect on the dose received by the exposed individual that was attributable to the repeated exposures. There was a diminished initial minute volume response in test challenges of both the upper and lower tracts of animals that had received at least 16 weeks of exposure to 15 ppm, with compensatory increases in tidal volume in the upper tract and respiratory rate in the lower tract. However, this dose-related effect was probably not relevant to human risk estimation because this formaldehyde dose is in excess of that experienced by human populations. ^