Predicting and reasoning about replicability using structured groups.

This paper explores judgements about the replicability of social and behavioural sciences research and what drives those judgements. Using a mixed methods approach, it draws on qualitative and quantitative data elicited from groups using a structured approach called the IDEA protocol ('investigate', 'discuss', 'estimate' and 'aggregate'). Five groups of five people with relevant domain expertise evaluated 25 research claims that were subject to at least one replication study.

Predicting reliability through structured expert elicitation with the repliCATS (Collaborative Assessments for Trustworthy Science) process.

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences.

Reimagining peer review as an expert elicitation process.

Journal peer review regulates the flow of ideas through an academic discipline and thus has the power to shape what a research community knows, actively investigates, and recommends to policymakers and the wider public. We might assume that editors can identify the 'best' experts and rely on them for peer review. But decades of research on both expert decision-making and peer review suggests they cannot.

Challenges in estimation, uncertainty quantification and elicitation for pandemic modelling.

The estimation of parameters and model structure for informing infectious disease response has become a focal point of the recent pandemic. However, it has also highlighted a plethora of challenges remaining in the fast and robust extraction of information using data and models to help inform policy. In this paper, we identify and discuss four broad challenges in the estimation paradigm relating to infectious disease modelling, namely the Uncertainty Quantification framework, data challenges in estimation, model-based inference and prediction, and expert judgement.

Uncertainty Quantification with Experts: Present Status and Research Needs.

Expert elicitation is deployed when data are absent or uninformative and critical decisions must be made. In designing an expert elicitation, most practitioners seek to achieve best practice while balancing practical constraints. The choices made influence the required time and effort investment, the quality of the elicited data, experts' engagement, the defensibility of results, and the acceptability of resulting decisions.

Weighting and aggregating expert ecological judgments.

Performance weighted aggregation of expert judgments, using calibration questions, has been advocated to improve pooled quantitative judgments for ecological questions. However, there is little discussion or practical advice in the ecological literature regarding the application, advantages or challenges of performance weighting. In this paper we (1) illustrate how the IDEA protocol with four-step question format can be extended to include performance weighted aggregation from the Classical Model, and (2) explore the extent to which this extension improves pooled judgments for a range of performance measures.

Prospective cohort study of procalcitonin levels in children with cancer presenting with febrile neutropenia.

Background: Febrile neutropenia (FNP) causes significant morbidity and mortality in children undergoing treatment for cancer. The development of clinical decision rules to help stratify risks in paediatric FNP patients and the use of inflammatory biomarkers to identify high risk patients is an area of recent research. This study aimed to assess if procalcitonin (PCT) levels could be used to help diagnose or exclude severe infection in children with cancer who present with febrile neutropenia, both as a single measurement and in addition to previously developed clinical decision rules.

Prevention of serious respiratory syncytial virus-related illness. II: Immunoprophylaxis.

Respiratory syncytial virus (RSV) causes significant morbidity in very young children, preterm infants with and without chronic lung disease, and children with hemodynamically significant congenital heart disease. In the absence of a safe and effective vaccine, alternative means of protecting high-risk infants and young children from serious RSV illness have been studied. Clinical observations and animal model data over the past 30 years suggested that RSV immunoglobulin G (IgG) neutralizing antibodies might offer protection from severe RSV lower respiratory tract disease.

Human herpes simplex viruses in benign and malignant thyroid tumours.

To test the hypothesis that herpes viruses may have a role in thyroid neoplasia, we analysed thyroid tissues from patients with benign (44) and malignant (65) lesions for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression, and activation of viral-inducible signalling pathways. Expression of viral entry receptor nectin-1 was examined in human samples and in cancer cell lines.

Characterization of late tuberculosis infection in Sigmodon hispidus.

We previously described primary tuberculosis in Sigmodon hispidus cotton rats up to 6 months following a pulmonary challenge. At that time, we observed fewer animals demonstrating disease as time from exposure progressed. We hypothesized that some cotton rats may control a primary infection to latency in a similar fashion to humans.

Association of TLR4 polymorphisms with symptomatic respiratory syncytial virus infection in high-risk infants and young children.

Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Although anti-RSV Ab prophylaxis has greatly reduced infant mortality in the United States, there is currently no vaccine or effective antiviral therapy. RSV fusion (F) protein activates cells through TLR4.

Respiratory syncytial virus replication is prolonged by a concomitant allergic response.

Epidemiological studies show an association between early exposure to respiratory syncytial virus (RSV) and the development or exacerbation of asthma. This idea is supported by studies in mice that demonstrate worsened airway hyper-reactivity (AHR) when RSV-infected animals are exposed to allergen. The effect of allergen on RSV disease, however, has not been reported.

The American cotton rat: a novel model for pulmonary tuberculosis.

Several animal models are used to study Mycobacterium tuberculosis (MTB) infections, but none is a fully ideal model of human disease. The American cotton rat is an excellent model for the study of several human viral and bacterial respiratory infectious diseases, but until now has not been reported to be a model with MTB infection. Preliminary experiments were designed in which two species of cotton rats (Sigmodon hispidus and Sigmodon fulviventer) received respiratory challenges with M.

Analysis of TLR4 polymorphic variants: new insights into TLR4/MD-2/CD14 stoichiometry, structure, and signaling.

TLR4 is the signal-transducing receptor for structurally diverse microbial molecules such as bacterial LPS, respiratory syncytial virus fusion (F) protein, and chlamydial heat shock protein 60. Previous studies associated two polymorphic mutations in the extracellular domain of TLR4 (Asp(299)Gly and Thr(399)Ile) with decreased LPS responsiveness. To analyze the molecular basis for diminished responsiveness, site-specific mutations (singly or coexpressed) were introduced into untagged and epitope (Flag)-tagged wild-type (WT) TLR4 expression vectors to permit a direct comparison of WT and mutant signal transduction.

Comparison of corticosteroids for treatment of respiratory syncytial virus bronchiolitis and pneumonia in cotton rats.

Triamcinolone acetonide, methylprednisolone, and dexamethasone were each evaluated in combination with palivizumab (Synagis) for the therapy of established respiratory syncytial virus infection in the cotton rat. Triamcinolone and methylprednisolone proved to be more effective than dexamethasone in reducing lung pathology. No recurrence of viral replication or pulmonary pathology followed the cessation of therapy.