Neurocognitive subprocesses of working memory performance.

Working memory (WM) has been defined as the active maintenance and flexible updating of goal-relevant information in a form that has limited capacity and resists interference. Complex measures of WM recruit multiple subprocesses, making it difficult to isolate specific contributions of putatively independent subsystems. The present study was designed to determine whether neurophysiological indicators of proposed subprocesses of WM predict WM performance. We recruited 200 individuals defined by care-seeking status and measured neural responses using electroencephalography (EEG), while participants performed four WM tasks. We extracted spectral and time-domain EEG features from each task to quantify each of the hypothesized WM subprocesses: maintenance (storage of content), goal maintenance, and updating. We then used EEG measures of each subprocess as predictors of task performance to evaluate their contribution to WM. Significant predictors of WM capacity included contralateral delay activity and frontal theta, features typically associated with maintenance (storage of content) processes. In contrast, significant predictors of reaction time and its variability included contingent negative variation and the P3b, features typically associated with goal maintenance and updating. Broadly, these results suggest two principal dimensions that contribute to WM performance, tonic processes during maintenance contributing to capacity, and phasic processes during stimulus processing that contribute to response speed and variability. The analyses additionally highlight that reliability of features across tasks was greater (and comparable to that of WM performance) for features associated with stimulus processing (P3b and alpha), than with maintenance (gamma, theta and cross-frequency coupling).

An evaluation of emerging vaccines for childhood pneumococcal pneumonia.

BACKGROUND: Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP) or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%). CONCLUSIONS: Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide.