Estimating Gene Interactions Using Information Theoretic Functionals

With an abundance of data resulting from high-throughput technologies, like DNA microarrays, a race has been on the last few years, to determine the structures and functions of genes and their products, the proteins. Inference of gene interactions, lies in the core of these efforts. In all this activity, three important research issues have emerged. First, in much of the current literature on gene regulatory networks, dependencies among variables in our case genes - are assumed to be linear in nature, when in fact, in real-life scenarios this is seldom the case. This disagreement leads to systematic deviation and biased evaluation. Secondly, although the problem of undersampling, features in every piece of work as one of the major causes for poor results, in practice it is overlooked and rarely addressed explicitly. Finally, inference of network structures, although based on rigid mathematical foundations and computational optimizations, often displays poor fitness values and biologically unrealistic link structures, due - to a large extend - to the discovery of pairwise only interactions. In our search for robust, nonlinear measures of dependency, we advocate that mutual information and related information theoretic functionals (conditional mutual information, total correlation) are possibly the most suitable candidates to capture both linear and nonlinear interactions between variables, and resolve higher order dependencies. To address these issues, we researched and implemented under a common framework, a selection nonparametric estimators of mutual information for continuous variables. The focus of their assessment was, their robustness to the limited sample sizes and their expansibility to higher dimensions - important for the detection of more complex interaction structures. Two different assessment scenaria were performed, one with simulated data and one with bootstrapping the estimators in state-of-the-art network inference algorithms and monitor their predictive power and sensitivity. The tests revealed that, in small sample size regimes, there is a significant difference in the performance of different estimators, and naive methods such as uniform binning, gave consistently poor results compared with more sophisticated methods. Finally, a custom, modular mechanism is proposed, for the inference of gene interactions, targeting the identi cation of some of the most common substructures in genetic networks, that we believe will help improve accuracy and predictability scores

The relationship between second language anxiety and international nursing students stress

Second language anxiety is a common phenomenon amongst international students. However, information on second language anxiety remains scarce, particularly amongst specific populations such as international nursing students. The study examined the relationship between second language anxiety and international nursing student stress after taking into account the demographic, cognitive, and acculturative factors. One hundred and fifty-two international nursing students completed an online questionnaire battery. Hierarchical regression analysis revealed that spoken second language anxiety and the acculturative factors of marginalisation and separation were significantly related to learning & teaching-related and placement-related stress in international nursing students. The results suggest that international nursing students are equally vulnerable to developing stress as a result of the pressures of their degree course, with second language anxiety, particularly its spoken aspect, being a significant component of this stress. As such, interventions aimed at building resilience in international students, particularly those in nursing programs, should factor in coping and management of second language issues into their programs, especially with respects to second language communication

Relating the metatranscriptome and metagenome of the human gut

Although the composition of the human microbiome is now wellstudied, the microbiota’s \u3e8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. Within-subject microbial species, gene, and transcript abundances were highly concordant across sampling methods, with only a small fraction of transcripts (\u3c5%) displaying between-method variation. Next, we investigated relationships between the oral and gut microbial communities, identifying a subset of abundant oral microbes that routinely survive transit to the gut, but with minimal transcriptional activity there. Finally, systematic comparison of the gut metagenome and metatranscriptome revealed that a substantial fraction (41%) of microbial transcripts were not differentially regulated relative to their genomic abundances. Of the remainder, consistently underexpressed pathways included sporulation and amino acid biosynthesis, whereas up-regulated pathways included ribosome biogenesis and methanogenesis. Across subjects, metatranscriptional profiles were significantly more individualized than DNA-level functional profiles, but less variable than microbial composition, indicative of subject-specific whole-community regulation. The results thus detail relationships between community genomic potential and gene expression in the gut, and establish the feasibility of metatranscriptomic investigations in subject-collected and shipped samples

Assessing diets of 3-year-old children:evaluation of an FFQ

OBJECTIVE: To evaluate the use of an administered eighty-item FFQ to assess nutrient intake and diet quality in 3-year-old children. DESIGN: Frequency of consumption and portion size of the foods listed on the FFQ during the 3 months preceding the interview were reported by the child's main caregiver; after the interview a 2 d prospective food diary (FD) was completed on behalf of the child. Nutrient intakes from the FFQ and FD were estimated using UK food composition data. Diet quality was assessed from the FFQ and FD according to the child's scores for a principal component analysis-defined dietary pattern ('prudent' pattern), characterised by high consumption of fruit, vegetables, water and wholemeal cereals. SETTING: Southampton, UK. SUBJECTS: Children (n 892) aged 3 years in the Southampton Women's Survey. RESULTS: Intakes of all nutrients assessed by the FFQ were higher than FD estimates, but there was reasonable agreement in terms of ranking of children (range of Spearman rank correlations for energy-adjusted nutrient intakes, r s = 0·41 to 0·59). Prudent diet scores estimated from the FFQ and FD were highly correlated (r = 0·72). Some family and child characteristics appeared to influence the ability of the FFQ to rank children, most notably the number of child's meals eaten away from home. CONCLUSIONS: The FFQ provides useful information to allow ranking of children at this age with respect to nutrient intake and quality of diet, but may overestimate absolute intakes. Dietary studies of young children need to consider family and child characteristics that may impact on reporting error associated with an FFQ

Benefits and challenges of electronic prescribing for general practitioners and pharmacists in regional Australia

Objective: To explore the benefits and challenges of electronic prescribing (e-prescribing) for general practitioners (GPs) and pharmacists in regional New South Wales (NSW). Methods: This qualitative study utilised semistructured interviews conducted virtually or in-person between July and September 2021. Setting and Participants: General practitioners and pharmacists practising in Bathurst NSW. Main Outcomes: Self-reported perceived and experienced benefits and challenges of e-prescribing. Results: Two GPs and four pharmacists participated in the study. Reported benefits of e-prescribing included improvement in the prescribing and dispensing process, patient adherence, and prescription safety and security. The increased convenience for the patients was appreciated particularly during the COVID-19 pandemic. Challenges discussed were how the system was perceived to be unsafe and insecure, costs of messaging and updating general practice software, utilisation of new systems and patient awareness. Pharmacists reported the need for education to patients and staff to minimise the impact of inexperience with the novel technology on workflow efficacy. Conclusion: This study provided first insight and information on the perspectives of GPs and pharmacists 12 months after the implementation of e-prescribing. Further nationwide studies are required to consolidate these findings; provide comparisons with the system's progress since conception; determine whether metropolitan and rural health care professionals share similar perspectives; and shed light on where additional government support may be required

Intravenous vitamin C in the treatment of post-laser hyperpigmentation for melasma: A short report

Melasma is difficult to treat. Vitamin C, topical and by iontophoresis, has been shown to be useful. When lasers are used, there is a significant incidence of post-laser hyperpigmentation. There is no single established treatment for the latter. The case history of a 51-year-old Chinese woman is presented. Intravenous vitamin C appears to be useful in treating this complication

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials