Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstructural changes in the brain due to amyloid-β (Aβ) plaque deposition. We longitudinally acquired DKI data of wild-type (WT) and APP/PS1 mice at 2, 4, 6 and 8 months of age, after which these mice were sacrificed for histological examination. Three additional cohorts of mice were also included at 2, 4 and 6 months of age to allow voxel-based co-registration between diffusion tensor and diffusion kurtosis metrics and immunohistochemistry. Changes were observed in diffusion tensor (DT) and diffusion kurtosis (DK) metrics in many of the 23 regions of interest that were analysed. Mean and axial kurtosis were greatly increased owing to Aβ-induced pathological changes in the motor cortex of APP/PS1 mice at 4, 6 and 8 months of age. Additionally, fractional anisotropy (FA) was decreased in APP/PS1 mice at these respective ages. Linear discriminant analysis of the motor cortex data indicated that combining diffusion tensor and diffusion kurtosis metrics permits improved separation of WT from APP/PS1 mice compared with either diffusion tensor or diffusion kurtosis metrics alone. We observed that mean kurtosis and FA are the critical metrics for a correct genotype classification. Furthermore, using a newly developed platform to co-register the in vivo diffusion-weighted magnetic resonance imaging with multiple 3D histological stacks, we found high correlations between DK metrics and anti-Aβ (clone 4G8) antibody, glial fibrillary acidic protein, ionised calcium-binding adapter molecule 1 and myelin basic protein immunohistochemistry. Finally, we observed reduced FA in the septal nuclei of APP/PS1 mice at all ages investigated. The latter was at least partially also observed by voxel-based statistical parametric mapping, which showed significantly reduced FA in the septal nuclei, as well as in the corpus callosum, of 8-month-old APP/PS1 mice compared with WT mice. Our results indicate that DKI metrics hold tremendous potential for the early detection and longitudinal follow-up of Aβ-induced pathology.

Safe and effective coronavirus disease–19 (COVID-19) vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged nonhuman primates (NHPs). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared with a single dose. In one-dose regimens, neutralizing antibody responses were stable for at least 14 wk, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and T helper cell (Th cell) 1–skewed cellular responses in aged NHPs that were comparable to those in adult animals. Aged Ad26.COV2.S-vaccinated animals challenged 3 mo after dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. Neutralization of variants of concern by NHP sera was reduced for B.1.351 lineages while maintained for the B.1.1.7 lineage independent of Ad26.COV2.S vaccine regimen.

Background: The importance of systematic reviews in collating and summarising available research output on a particular topic cannot be over-emphasized. However, initial screening of retrieved literature is significantly time and labour intensive. Attempts at automating parts of the systematic review process have been made with varying degree of success partly due to being domain-specific, requiring vendor-specific software or manually labelled training data. Our primary objective was to develop statistical methodology for performing automated title and abstract screening for systematic reviews. Secondary objectives included (1) to retrospectively apply the automated screening methodology to previously manually screened systematic reviews and (2) to characterize the performance of the automated screening methodology scoring algorithm in a simulation study. Methods: We implemented a Latent Dirichlet Allocation-based topic model to derive representative topics from the retrieved documents’ title and The second step involves defining a score threshold for classifying the documents as relevant for full-text review or not. The score is derived based on a set of search keywords (often the database retrieval search terms). Two systematic review studies were retrospectively used to illustrate the methodology. Results: In one case study (helminth dataset), $$69.83\%$$69.83 % sensitivity compared to manual title and abstract screening was achieved. This is against a false positive rate of $$22.63\%$$22.63 % . For the second case study (Wilson disease dataset), a sensitivity of $$54.02\%$$54.02 % and specificity of $$67.03\%$$67.03 % were achieved. Conclusions: Unsupervised title and abstract screening has the potential to reduce the workload involved in conducting systematic review. While sensitivity of the methodology on the tested data is low, approximately $$70\%$$70 % specificity was achieved. Users ought to keep in mind that potentially low sensitivity might occur. One approach to mitigate this might be to incorporate additional targeted search keywords such as the indexing databases terms into the search term copora. Moreover, automated screening can be used as an additional screener to the manual screeners.

Unsupervised statistical analysis of unstructured data has gained wide acceptance especially in natural language processing and text mining domains. Topic modelling with Latent Dirichlet Allocation is one such statistical tool that has been successfully applied to synthesize collections of legal, biomedical documents and journalistic topics. We applied a novel two-stage topic modelling approach and illustrated the methodology with data from a collection of published abstracts from the University of Nairobi, Kenya. In the first stage, topic modelling with Latent Dirichlet Allocation was applied to derive the per-document topic probabilities. To more succinctly present the topics, in the second stage, hierarchical clustering with Hellinger distance was applied to derive the final clusters of topics. The analysis showed that dominant research themes in the university include: HIV and malaria research, research on agricultural and veterinary services as well as cross-cutting themes in humanities and social sciences. Further, the use of hierarchical clustering in the second stage reduces the discovered latent topics to clusters of homogeneous topics.

Dissolved oxygen is an essential controlling factor in the performance of facultative and maturation ponds since both take many advantages of algal photosynthetic oxygenation. The rate of this photosynthesis strongly depends on the time during the day and the location in a pond system, whose roles have been overlooked in previous guidelines of pond operation and maintenance (O&M). To elucidate these influences, a linear mixed effect model (LMM) was built on the data collected from three intensive sampling campaigns in a waste stabilization pond in Cuenca, Ecuador. Within two parallel lines of facultative and maturation ponds, nine locations were sampled at two depths in each pond. In general, the output of the mixed model indicated high spatial autocorrelations of data and wide spatiotemporal variations of the oxygen level among and within the ponds. Particularly, different ponds showed different patterns of oxygen dynamics, which were associated with many factors including flow behavior, sludge accumulation, algal distribution, influent fluctuation, and pond function. Moreover, a substantial temporal change in the oxygen level between day and night, from zero to above 20 mg O₂·L⁻¹, was observed. Algal photosynthetic activity appeared to be the main reason for these variations in the model, as it was facilitated by intensive solar radiation at high altitude. Since these diurnal and spatial patterns can supply a large amount of useful information on pond performance, insightful recommendations on dissolved oxygen (DO) monitoring and regulations were delivered. More importantly, as a mixed model showed high predictive performance, i.e., high goodness-of-fit (R² of 0.94), low values of mean absolute error, we recommended this advanced statistical technique as an effective tool for dealing with high autocorrelation of data in pond systems.