The Hope and Adaptation Scale (HAS): establishing face and content validity

Purpose: To develop and test the face and content validity of a scale that assesses an individual’s adaptation and expression of hope to a life changing events, disease or trauma. Method: The Hope and Adaptation Scale was developed and tested across three stages. Stage 1 involved the use of a review of literature to conceptually map the tool. Stage 2 required exploratory investigations of the questionnaire by members of an expert panel. Stage 3 assessed the construct validity of the resulting scale. Results: Through the processes of Stage 1 and 2, the tool was developed and reduced to a 3-item scale that assessed a spectrum of hope-related responses and a spectrum of adaptation-related responses. Stage 3 identified fifteen independent health care professionals who assessed the scale. The content validity index of the resultant scale was 0.6 that was above the required level to be acceptable. The hope spectrum responses scored the highest content validity ratio (0.73). Discussion: The proposed scale appears to have face and content validity for application to a various number of events, disease or trauma experiences. Further testing of the scale is required for application in specific population groups

Mapping of interaction sites of the Schizosaccharomyces pombe protein Translin with nucleic acids and proteins: a combined molecular genetics and bioinformatics study

Translin is a single-stranded RNA- and DNA-binding protein, which has been highly conserved in eukaryotes, from man to Schizosaccharomyces pombe. TRAX is a Translin paralog associated with Translin, which has coevolved with it. We generated structural models of the S. pombe Translin (spTranslin), based on the solved 3D structure of the human ortholog. Using several bioinformatics computation tools, we identified in the equatorial part of the protein a putative nucleic acids interaction surface, which includes many polar and positively charged residues, mostly arginines, surrounding a shallow cavity. Experimental verification of the bioinformatics predictions was obtained by assays of nucleic acids binding to amino acid substitution variants made in this region. Bioinformatics combined with yeast two-hybrid assays and proteomic analyses of deletion variants, also identified at the top of the spTranslin structure a region required for interaction with spTRAX, and for spTranslin dimerization. In addition, bioinformatics predicted the presence of a second protein-protein interaction site at the bottom of the spTranslin structure. Similar nucleic acid and protein interaction sites were also predicted for the human Translin. Thus, our results appear to generally apply to the Translin family of proteins, and are expected to contribute to a further elucidation of their functions

Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)

BACKGROUND:Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS:Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51-65, 71-90, 131-170, 196-210 and 246-260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51-65), 27 and 28 (aa131-150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51-65, 131-170, 196-210 and 246-260 elicited the highest antibody response and epitopes131-170, 196-210 and 246-260, elicited IFN-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE:Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine

Multi-objective genetic algorithms in the study of the genetic code’s adaptability

Using a robustness measure based on values of the polar requirement of amino acids, Freeland and Hurst (1998) showed that less than one in one million random hypothetical codes are better than the standard genetic code. In this paper, instead of comparing the standard code with randomly generated codes, we use an optimisation algorithm to find the best hypothetical codes. This approach has been used before, but considering only one objective to be optimised. The robustness measure based on the polar requirement is considered the most effective objective to be optimised by the algorithm. We propose here that the polar requirement is not the only property to be considered when computing the robustness of the genetic code. We include the hydropathy index and molecular volume in the evaluation of the amino acids using three multi-objective approaches: the weighted formula, lexicographic and Pareto approaches. To our knowledge, this is the first work proposing multi-objective optimisation approaches with a non-restrictive encoding for studying the evolution of the genetic code. Our results indicate that multi-objective approaches considering the three amino acid properties obtain better results than those obtained by single objective approaches reported in the literature. The codes obtained by the multi-objective approach are more robust and structurally more similar to the standard code

Section 230 and the Future of Free Speech on the Internet

In today’s episode, Rick and Sam are joined by William & Mary law school professor Laura Heymann to discuss Section 230, which recently has been in the news as people across the political spectrum have called for its repeal. The conversation begins by examining the nature and intent of Section 230 and why internet content is treated differently from newspaper or book publishers. The discussion then dives deeper into the implications of Section 230 on the First Amendment and free speech generally, along with the costs and benefits of social media and internet content as it relates to civil discourse

Section 230 and the Future of Free Speech on the Internet

In today’s episode, Rick and Sam are joined by William & Mary law school professor Laura Heymann to discuss Section 230, which recently has been in the news as people across the political spectrum have called for its repeal. The conversation begins by examining the nature and intent of Section 230 and why internet content is treated differently from newspaper or book publishers. The discussion then dives deeper into the implications of Section 230 on the First Amendment and free speech generally, along with the costs and benefits of social media and internet content as it relates to civil discourse

The impact of patient-reported outcome data from clinical trials: perspectives from international stakeholders.

BACKGROUND Patient-reported outcomes (PROs) are increasingly collected in clinical trials as they provide unique information on the physical, functional and psychological impact of a treatment from the patient's perspective. Recent research suggests that PRO trial data have the potential to inform shared decision-making, support pharmaceutical labelling claims and influence healthcare policy and practice. However, there remains limited evidence regarding the actual impact associated with PRO trial data and how to maximise PRO impact to benefit patients and society. Thus, our objective was to qualitatively explore international stakeholders' perspectives surrounding: a) the impact of PRO trial data, b) impact measurement metrics, and c) barriers and facilitators to effectively maximise the impact of PRO trial data upon patients and society. METHODS Semi-structured interviews with 24 international stakeholders were conducted between May and October 2018. Data were coded and analysed using reflexive thematic analysis. RESULTS International stakeholders emphasised the impact of PRO trial data to benefit patients and society. Influence on policy-impact, including changes to clinical healthcare practice and guidelines, drug approval and promotional labelling claims were common types of PRO impact reported by interviewees. Interviewees suggested impact measurement metrics including: number of pharmaceutical labelling claims and interviews with healthcare practitioners to determine whether PRO data were incorporated in clinical decision-making. Key facilitators to PRO impact highlighted by stakeholders included: standardisation of PRO tools; consideration of health utilities when selecting PRO measures; adequate funding to support PRO research; improved reporting and dissemination of PRO trial data by key opinion leaders and patients; and development of legal enforcement of the collection of PRO data. CONCLUSIONS Determining the impact of PRO trial data is essential to better allocate funds, minimise research waste and to help maximise the impact of these data for patients and society. However, measuring the impact of PRO trial data through metrics is a challenging task, as current measures do not capture the total impact of PRO research. Broader international multi-stakeholder engagement and collaboration is needed to standardise PRO assessment and maximise the impact of PRO trial data to benefit patients and society