The Program for climate Model diagnosis and Intercomparison: 20-th anniversary Symposium

Twenty years ago, W. Lawrence (Larry) Gates approached the U.S. Department of Energy (DOE) Office of Energy Research (now the Office of Science) with a plan to coordinate the comparison and documentation of climate model differences. This effort would help improve our understanding of climate change through a systematic approach to model intercomparison. Early attempts at comparing results showed a surprisingly large range in control climate from such parameters as cloud cover, precipitation, and even atmospheric temperature. The DOE agreed to fund the effort at the Lawrence Livermore National Laboratory (LLNL), in part because of the existing computing environment and because of a preexisting atmospheric science group that contained a wide variety of expertise. The project was named the Program for Climate Model Diagnosis and Intercomparison (PCMDI), and it has changed the international landscape of climate modeling over the past 20 years. In spring 2009 the DOE hosted a 1-day symposium to celebrate the twentieth anniversary of PCMDI and to honor its founder, Larry Gates. Through their personal experiences, the morning presenters painted an image of climate science in the 1970s and 1980s, that generated early support from the international community for model intercomparison, thereby bringing PCMDI into existence. Four talks covered GatesÃÂâÃÂÃÂÃÂÃÂs early contributions to climate research at the University of California, Los Angeles (UCLA), the RAND Corporation, and Oregon State University through the founding of PCMDI to coordinate the Atmospheric Model Intercomparison Project (AMIP). The speakers were, in order of presentation, Warren Washington [National Center for Atmospheric Research (NCAR)], Kelly Redmond (Western Regional Climate Center), George Boer (Canadian Centre for Climate Modelling and Analysis), and Lennart Bengtsson [University of Reading, former director of the European Centre for Medium-Range Weather Forecasts (ECMWF)]. The afternoon session emphasized the scientific ideas that are the basis of PCMDIÃÂâÃÂÃÂÃÂÃÂs success, summarizing their evolution and impact. Four speakers followed the various PCMDI-supported climate model intercomparison projects, beginning with early work on cloud representations in models, presented by Robert D. Cess (Distinguished Professor Emeritus, Stony Brook University), and then the latest Cloud Feedback Model Intercomparison Projects (CFMIPs) led by Sandrine Bony (Laboratoire de MÃÂÃÂÃÂétÃÂÃÂÃÂéorologie Dynamique). Benjamin Santer (LLNL) presented a review of the climate change detection and attribution (D & A) work pioneered at PCMDI, and Gerald A. Meehl (NCAR) ended the day with a look toward the future of climate change research

Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous disease is reversed by IFN-γ in a nitric oxide-dependent manner

Immunodeficiency in chronic granulomatous disease (CGD) is well characterized. Less understood are exaggerated sterile inflammation and autoimmunity associated with CGD. Impaired recognition and clearance of apoptotic cells resulting in their disintegration may contribute to CGD inflammation. We hypothesized that priming of macrophages (Ms) with IFN-γ would enhance impaired engulfment of apoptotic cells in CGD. Diverse M populations from CGD (gp91(phox)(-/-)) and wild-type mice, as well as human Ms differentiated from monocytes and promyelocytic leukemia PLB-985 cells (with and without mutation of the gp91(phox)), demonstrated enhanced engulfment of apoptotic cells in response to IFN-γ priming. Priming with IFN-γ was also associated with increased uptake of Ig-opsonized targets, latex beads, and fluid phase markers, and it was accompanied by activation of the Rho GTPase Rac. Enhanced Rac activation and phagocytosis following IFN-γ priming were dependent on NO production via inducible NO synthase and activation of protein kinase G. Notably, endogenous production of TNF-α in response to IFN-γ priming was critically required for inducible NO synthase upregulation, NO production, Rac activation, and enhanced phagocytosis. Treatment of CGD mice with IFN-γ also enhanced uptake of apoptotic cells by M in vivo via the signaling pathway. Importantly, during acute sterile peritonitis, IFN-γ treatment reduced excess accumulation of apoptotic neutrophils and enhanced phagocytosis by CGD Ms. These data support the hypothesis that in addition to correcting immunodeficiency in CGD, IFN-γ priming of Ms restores clearance of apoptotic cells and may thereby contribute to resolution of exaggerated CGD inflammation

Virtual reality relaxation for people with mental health conditions: a systematic review.

PURPOSE: Vulnerability to stress is linked to poor mental health. Stress management interventions for people with mental health conditions are numerous but they are difficult to implement and have limited effectiveness in this population. Virtual reality (VR) relaxation is an innovative intervention that aims to reduce stress. This review aimed to synthesize evidence of VR relaxation for people with mental health conditions (PROSPERO 269405). METHODS: Embase, Medline, PsycInfo, and Web of Science were searched until 17th September 2021. The review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Effective Public Health Practice Project (EPHPP) tool assessed methodological quality of studies. RESULTS: Searching identified 4550 studies. Eighteen studies (N = 848) were included in the review. Studies were published between 2008 and 2021. Eleven were conducted in Europe. Thirteen studies were controlled trials. Participants were mostly working-age adult outpatients experiencing anxiety or stress-related conditions. Other conditions included eating disorders, depression, bipolar disorder, and psychosis. Five studies tested inpatients. All studies used a range of nature-based virtual environments, such as forests, islands, mountains, lakes, waterfalls, and most commonly, beaches to promote relaxation. Studies provided evidence of the feasibility, acceptability, and short-term effectiveness of VR relaxation to increase relaxation and reduce stress. EPHPP ratings were 'strong' (N = 11), 'moderate' (N = 4), and 'weak' (N = 3). CONCLUSIONS: VR relaxation has potential as a low-intensity intervention to promote relaxation and reduce stress for adults with mental health conditions, especially anxiety and stress-related problems. Further research is warranted on this promising intervention

Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

Elephants in pyjamas: testing the weak central coherence account of autism spectrum disorders using a syntactic disambiguation task

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status

Autoantibodies to Osteoprotegerin are Associated with Low Hip Bone Mineral Density and History of Fractures in Axial Spondyloarthritis: A Cross-Sectional Observational Study

Osteoporosis is a recognised complication of axial spondyloarthritis (axSpA) and is thought to be due to functional impairment and the osteoclast-activating effects of proinflammatory cytokines. The development of autoantibodies to OPG (OPG-Ab) has been associated with severe osteoporosis and increased bone resorption in rheumatoid arthritis. In this study, we screened for the presence of OPG-Ab in axSpA and reviewed their clinical significance. We studied 134 patients, recruited from two centres in the United Kingdom. Their mean age was 47.5 years and 75% were male. Concentrations of OPG-Ab were related to bone mineral density (BMD) and fracture history using linear and logistic regression models adjusting for age, gender, disease duration and activity, body mass index and bisphosphonate use. We detected OPG-Ab in 11/134 patients (8.2%). Femoral neck and total hip BMD were significantly reduced in OPG-Ab positive patients (0.827 vs. 0.967 g/cm2, p = 0.008 and 0.868 vs. 1.028 g/cm2, p = 0.002, respectively). Regression analysis showed that the presence of OPG-Ab was independently associated with total hip osteopenia (ORadj 24.2; 95% CI 2.57, 228) and history of fractures (ORadj 10.5; 95% CI 2.07, 53.3). OPG-Ab concentration was associated with total hip BMD in g/cm2 (ß = −1.15; 95% CI −0.25, −0.04). There were no associations between OPG-Ab concentration and bone turnover markers, but free sRANKL concentrations were lower in OPG-Ab-positive patients (median 0.04 vs. 0.11 pmol/L, p = 0.050). We conclude that OPG-Ab are associated with hip BMD and fractures in axSpA suggesting that they may contribute to the pathogenesis of bone loss in some patients with this condition

Characterisation of tetanus monoclonal antibodies as a first step towards the development of an in vitro vaccine potency immunoassay

Batch release testing for human and veterinary tetanus vaccines still relies heavily on methods that involve animals, particularly for potency testing. The quantity and quality of tetanus antigen present in these products is of utmost importance for product safety and clinical effect. Immunochemical methods that measure consistency of antigen content and quality, potentially as an indicator of potency, could be a better choice and negate the need for an in vivo potency test. These immunochemical methods require at least one well characterised monoclonal antibody (mAb) that is specific for the target antigen. In this paper we report the results of the comprehensive characterisation of a panel of mAbs against tetanus with a view to select antibodies that can be used for development of an in vitro potency immunoassay. We have assessed binding of the antibodies to native antigen (toxin), detoxified antigen (toxoid), adsorbed antigen and heat-altered antigen. Antibody function was determined using an in-house cell-based neutralisation assay to support prior in vivo potency data that was available for some, but not all, of the antibodies. In addition, antibody affinity was measured, and epitope competition analysis was performed to identify pairs of antibodies that could be deployed in a sandwich immunoassay format. Not all characterisation tests provided evidence of “superiority” of one mAb over another, but together the results from all characterisation studies allowed for selection of an antibody pair to be taken forward to assay development