102 research outputs found
Investigating the Effect of Trust Manipulations on Affect over Time in Human-Human versus Human-Robot Interactions
The current study explored the influence of trust and distrust behaviors on affect over time. We examined the differences in affect when participants (N=97) were paired with a human or a robot while playing amodified version of the investorgame. Results indicated that there were no differences in affect between partner types when the partner performed a trustful behavior. When the partner performed a distrustful behavior, positive affect was higher for human partners than for robot partners. When robot partners performed a distrustful behavior, negative affect had a steeper incline compared to human partners. These findings suggest that people are more sensitive to distrust behaviors that are performed by a robot over a human
Understanding the limits to generalizability of experimental evolutionary models.
Post print version of article deposited in accordance with SHERPA RoMEO guidelines. The final definitive version is available online at: http://www.nature.com/nature/journal/v455/n7210/abs/nature07152.htmlGiven the difficulty of testing evolutionary and ecological theory in situ, in vitro model systems are attractive alternatives; however, can we appraise whether an experimental result is particular to the in vitro model, and, if so, characterize the systems likely to behave differently and understand why? Here we examine these issues using the relationship between phenotypic diversity and resource input in the T7-Escherichia coli co-evolving system as a case history. We establish a mathematical model of this interaction, framed as one instance of a super-class of host-parasite co-evolutionary models, and show that it captures experimental results. By tuning this model, we then ask how diversity as a function of resource input could behave for alternative co-evolving partners (for example, E. coli with lambda bacteriophages). In contrast to populations lacking bacteriophages, variation in diversity with differences in resources is always found for co-evolving populations, supporting the geographic mosaic theory of co-evolution. The form of this variation is not, however, universal. Details of infectivity are pivotal: in T7-E. coli with a modified gene-for-gene interaction, diversity is low at high resource input, whereas, for matching-allele interactions, maximal diversity is found at high resource input. A combination of in vitro systems and appropriately configured mathematical models is an effective means to isolate results particular to the in vitro system, to characterize systems likely to behave differently and to understand the biology underpinning those alternatives
International Consortium for Health Outcomes Measurement (ICHOM): Standardized Patient-Centered Outcomes Measurement Set for Heart Failure Patients
Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group's objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide
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Oxidation of Low-Density Lipoprotein by Iron at Lysosomal pH: Implications for Atherosclerosis
Low density lipoprotein (LDL) has recently been shown to be oxidised by iron within the lysosomes of macrophages and this is a novel potential mechanism for LDL oxidation in atherosclerosis. Our aim was to characterise the chemical and physical changes induced in LDL by iron at lysosomal pH and to investigate the effects of iron chelators and α-tocopherol on this process. LDL was oxidised by iron at pH 4.5 and 37°C and its oxidation monitored by spectrophotometry and HPLC. LDL was oxidised effectively by FeSO4 (5-50 µM) and became highly aggregated at pH 4.5, but not at pH 7.4. Cholesteryl esters decreased and after a pronounced lag 7-ketocholesterol increased greatly. Total hydroperoxides (measured by tri-iodide assay) increased up to 24 h and then decreased only slowly. The lipid composition after 12 h at pH 4.5 and 37°C was similar to that of LDL oxidised by copper at pH 7.4 and 4°C, i.e. rich in hydroperoxides but low in oxysterols. Previously oxidised LDL aggregated rapidly and spontaneously at pH 4.5, but not at pH 7.4. Ferrous was much more effective than ferric iron at oxidising LDL when added after the oxidation was already underway. The iron chelators diethylenetriaminepentaacetic acid and, to a lesser extent, desferrioxamine inhibited LDL oxidation when added during its initial stages, but were unable to prevent LDL aggregating after it had been partially oxidised. Surprisingly, desferrioxamine increased the rate of LDL modification when added late in the oxidation process. α-Tocopherol enrichment of LDL initially increased the oxidation of LDL, but inhibited it later. The presence of oxidised and highly aggregated lipid within lysosomes has the potential to perturb the function of these organelles and to promote atherosclerosis
Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases
Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti–PD-1 antibody that bound membrane-proximally excluded CD45, triggered SHP2 phosphatase recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti–PD-1 blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer
Is the meiofauna a good indicator for climate change and anthropogenic impacts?
Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research
Barriers and facilitators to implement shared decision making in multidisciplinary sciatica care: a qualitative study
A new key player in VEGF-dependent angiogenesis in human hepatocellular carcinoma: dimethylarginine dimethylaminohydrolase 1
Improving outcomes for patients with lymphoma: design and development of the Australian and New Zealand Lymphoma and Related Diseases Registry
Background
Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly diverse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and other research activities. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process.
Methods
The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre.
Results
To date more than 5,300 patients have been enrolled from 28 sites in Australia and New Zealand. Multiple challenges arose during the development, which we describe, along with approaches used to overcome them. Several confirmed international collaborations are now in place, and the registry is providing valuable data for clinicians, researchers, industry and government, including through presentations of results at major national and international conferences.
Conclusion
Challenges in establishing the LaRDR have been successfully overcome and the registry is now a valuable resource for lymphoma clinicians, researchers, health economists and others in Australia, New Zealand and globally
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