Envisioning the Future of Academic Libraries

A group of librarians, other information professionals, scientists and research administrators met to discuss the challenges that research libraries are currently facing. After the meeting a survey was conducted to obtain additional input from the group on several key challenges that arose from the discussions. The purpose of the meeting and survey was threefold: 1. Examine in detail, from a variety of perspectives, how the world of research is changing and the impact these changes have on the direction of research libraries. 2. Create an informed vision of how research libraries can be a vital partner to researchers. 3. Suggest a strategic approach for realizing this vision. The strategic approach presented in this white paper incorporates feedback from various sized research libraries, each with its own mission.The expectation is that individual libraries will use it as a guide in formulating strategies that are appropriate to their research communities, financial circumstances, and organizational reporting structur

Methods for exploring the faecal microbiome of premature infants: a review

The premature infant gut microbiome plays an important part in infant health and development, and recognition of the implications of microbial dysbiosis in premature infants has prompted significant research into these issues. The approaches to designing investigations into microbial populations are many and varied, each with its own benefits and limitations. The technique used can influence results, contributing to heterogeneity across studies. This review aimed to describe the most common techniques used in researching the preterm infant microbiome, detailing their various limitations. The objective was to provide those entering the field with a broad understanding of available methodologies, so that the likely effects of their use can be factored into literature interpretation and future study design. We found that although many techniques are used for characterising the premature infant microbiome, 16S rRNA short amplicon sequencing is the most common. 16S rRNA short amplicon sequencing has several benefits, including high accuracy, discoverability and high throughput capacity. However, this technique has limitations. Each stage of the protocol offers opportunities for the injection of bias. Bias can contribute to variability between studies using 16S rRNA high throughout sequencing. Thus, we recommend that the interpretation of previous results and future study design be given careful consideration

To Probiotic or Not to Probiotic: A Metagenomic Comparison of the Discharge Gut Microbiome of Infants Supplemented With Probiotics in NICU and Those Who Are Not

Background: Preterm birth is associated with the development of both acute and chronic disease, and the disruption of normal gut microbiome development. Recent studies have sought to both characterize and understand the links between disease and the microbiome. Probiotic treatment may correct for these microbial imbalances and, in turn, mitigate disease. However, the criteria for probiotic supplementation in NICU's in North Queensland, Australia limits its usage to the most premature (<32 weeks gestation) and small for gestational age infants (<1,500 g). Here we use a combination of amplicon and shotgun metagenomic sequencing to compare the gut microbiome of infants who fulfill the criteria for probiotic-treatment and those who do not. The aims of this study were to determine if probiotic-supplemented preterm infants have significantly different taxonomic and functional profiles when compared to non-supplemented preterm infants at discharge. Methods: Preterm infants were recruited in North Queensland, Australia, with fecal samples collected just prior to discharge (36 ± 0.5 weeks gestation), to capture potential changes that could be probiotic induced. All samples underwent 16S rRNA gene amplicon sequencing, with a subset also used for shotgun metagenomics. Mixed effects models were used to assess the effect of probiotics on alpha diversity, beta diversity and taxonomic abundance, whilst accounting for other known covariates. Results: Mixed effects modeling demonstrated that probiotic treatment had a significant effect on overall community composition (beta diversity), characterized by greater alpha diversity and differing abundances of several taxa, including Bifidobacterium and Lactobacillus, in supplemented infants. Conclusion: Late preterm-infants who go without probiotic-supplementation may be missing out on stabilizing-effects provided through increased alpha diversity and the presence of commensal microbes, via the use of probiotic-treatment. These findings suggest that late-preterm infants may benefit from probiotic supplementation. More research is needed to both understand the consequences of the differences observed and the long-term effects of this probiotic-treatment

The bacterial gut microbiome of probiotic-treated very-preterm infants: changes from admission to discharge

Background: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used amplicon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables. Methods: Infants born <32 weeks gestation and <1500 g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal samples were collected at admission and discharge. All samples underwent 16S rRNA short amplicon sequencing, and subsequently, a combination of univariate and multivariate analyses. Results: 71 admission and 63 discharge samples were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha diversity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preeclampsia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa. Conclusions: The lower microbial diversity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates

Exploring the long-term colonisation and persistence of probiotic-prophylaxis species on the gut microbiome of preterm infants: a pilot study

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n= 18), at similar to 18 months of age, and a longitudinal analysis (n= 6), from admission to 18 months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran (R), as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped. Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training

Putting Food on The Table Project Toolkit

A toolkit to help community groups and members understand and address the food security needs of older adults in their community.https://source.sheridancollege.ca/centres_elder_food_toolkit/1000/thumbnail.jp

Evolution of Resistance to Targeted Anti-Cancer Therapies during Continuous and Pulsed Administration Strategies

The discovery of small molecules targeted to specific oncogenic pathways has revolutionized anti-cancer therapy. However, such therapy often fails due to the evolution of acquired resistance. One long-standing question in clinical cancer research is the identification of optimum therapeutic administration strategies so that the risk of resistance is minimized. In this paper, we investigate optimal drug dosing schedules to prevent, or at least delay, the emergence of resistance. We design and analyze a stochastic mathematical model describing the evolutionary dynamics of a tumor cell population during therapy. We consider drug resistance emerging due to a single (epi)genetic alteration and calculate the probability of resistance arising during specific dosing strategies. We then optimize treatment protocols such that the risk of resistance is minimal while considering drug toxicity and side effects as constraints. Our methodology can be used to identify optimum drug administration schedules to avoid resistance conferred by one (epi)genetic alteration for any cancer and treatment type

Accuracy of the Mologic COVID-19 rapid antigen test: a prospective multi-centre analytical and clinical evaluation

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the reliance on antigen detection rapid diagnostic tests (Ag-RDTs). Their evaluation at point of use is a priority. Methods: Here, we report a multi-centre evaluation of the analytical sensitivity, specificity, and clinical accuracy of the Mologic COVID-19 Ag-RDT by comparing to reverse transcriptase polymerase chain reaction (RT-qPCR) results from individuals with and without COVID-19 symptoms. Participants had attended hospitals in Merseyside, hospital and ambulance services in Yorkshire, and drive-through testing facilities in Northumberland, UK. Results: The limit of detection of the Mologic COVID-19 Ag-RDT was 5.0 x 102 pfu/ml in swab matrix with no cross-reactivity and interference for any other pathogens tested. A total of 347 participants were enrolled from 26th of November 2020 to 15th of February 2021 with 39.2% (CI 34.0-44.6) testing RT-qPCR positive for SARS-CoV-2. The overall sensitivity and specificity of the Mologic Ag-RDT compared to the reference SARS-CoV-2 RT-qPCR were 85.0% (95% CI 78.3-90.2) and 97.8% (95.0-99.3), respectively. Sensitivity was stratified by RT-qPCR cycle threshold (Ct) and 98.4% (91.3-100) of samples with a Ct less than 20 and 93.2% (86.5-97.2) of samples with a Ct less than 25 were detected using the Ag-RDT. Clinical accuracy was stratified by sampling strategy, swab type and clinical presentation. Mologic COVID-19 Ag-RDT demonstrated highest sensitivity with nose/throat swabs compared with throat or nose swabs alone; however, the differences were not statistically significant. Conclusions: Overall, the Mologic test had high diagnostic accuracy across multiple different settings, different demographics, and on self-collected swab specimens. These findings suggest the Mologic rapid antigen test may be deployed effectively across a range of use settings

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation