Dissecting human population variation in single-cell responses to SARS-CoV-2.

Humans display substantial interindividual clinical variability after SARS-CoV-2 infection1-3, the genetic and immunological basis of which has begun to be deciphered4. However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells-from 222 healthy donors of diverse ancestries-that were stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces weaker, but more heterogeneous, interferon-stimulated gene activity compared with influenza A virus, and a unique pro-inflammatory signature in myeloid cells. Transcriptional responses to viruses display marked population differences, primarily driven by changes in cell abundance including increased lymphoid differentiation associated with latent cytomegalovirus infection. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell composition on population disparities in immune responses, with genetic variants exerting a strong effect on specific loci. Furthermore, we show that natural selection has increased population differences in immune responses, particularly for variants associated with SARS-CoV-2 response in East Asians, and document the cellular and molecular mechanisms by which Neanderthal introgression has altered immune functions, such as the response of myeloid cells to viruses. Finally, colocalization and transcriptome-wide association analyses reveal an overlap between the genetic basis of immune responses to SARS-CoV-2 and COVID-19 severity, providing insights into the factors contributing to current disparities in COVID-19 risk.

High-throughput droplet-based analysis of influenza A virus genetic reassortment by single-virus RNA sequencing.

The segmented RNA genome of influenza A viruses (IAVs) enables viral evolution through genetic reassortment after multiple IAVs coinfect the same cell, leading to viruses harboring combinations of eight genomic segments from distinct parental viruses. Existing data indicate that reassortant genotypes are not equiprobable; however, the low throughput of available virology techniques does not allow quantitative analysis. Here, we have developed a high-throughput single-cell droplet microfluidic system allowing encapsulation of IAV-infected cells, each cell being infected by a single progeny virion resulting from a coinfection process. Customized barcoded primers for targeted viral RNA sequencing enabled the analysis of 18,422 viral genotypes resulting from coinfection with two circulating human H1N1pdm09 and H3N2 IAVs. Results were highly reproducible, confirmed that genetic reassortment is far from random, and allowed accurate quantification of reassortants including rare events. In total, 159 out of the 254 possible reassortant genotypes were observed but with widely varied prevalence (from 0.038 to 8.45%). In cells where eight segments were detected, all 112 possible pairwise combinations of segments were observed. The inclusion of data from single cells where less than eight segments were detected allowed analysis of pairwise cosegregation between segments with very high confidence. Direct coupling analysis accurately predicted the fraction of pairwise segments and full genotypes. Overall, our results indicate that a large proportion of reassortant genotypes can emerge upon coinfection and be detected over a wide range of frequencies, highlighting the power of our tool for systematic and exhaustive monitoring of the reassortment potential of IAVs.

Genetic susceptibility to severe childhood asthma and rhinovirus-C maintained by balancing selection in humans for 150 000 years.

Selective pressures imposed by pathogens have varied among human populations throughout their evolution, leading to marked inter-population differences at some genes mediating susceptibility to infectious and immune-related diseases. Here, we investigated the evolutionary history of a common polymorphism resulting in a Y529 versus C529 change in the cadherin related family member 3 (CDHR3) receptor which underlies variable susceptibility to rhinovirus-C infection and is associated with severe childhood asthma. The protective variant is the derived allele and is found at high frequency worldwide (69-95%). We detected genome-wide significant signatures of natural selection consistent with a rapid increase of the haplotypes carrying the allele, suggesting that non-neutral processes have acted on this locus across all human populations. However, the allele has not fixed in any population despite multiple lines of evidence suggesting that the mutation predates human migrations out of Africa. Using an approximate Bayesian computation method, we estimate the age of the mutation while explicitly accounting for past demography and positive or frequency-dependent balancing selection. Our analyses indicate a single emergence of the mutation in anatomically modern humans ~150 000 years ago and indicate that balancing selection has maintained the beneficial allele at high equilibrium frequencies worldwide. Apart from the well-known cases of the MHC and ABO genes, this study provides the first evidence that negative frequency-dependent selection plausibly acted on a human disease susceptibility locus, a form of balancing selection compatible with typical transmission dynamics of communicable respiratory viruses that might exploit CDHR3.

The development and validation of a medicines optimisation tool to protect the physical health of people with severe mental illness (OPTIMISE).

BACKGROUND: The life expectancy of people with severe mental illness (SMI) is shorter than those without SMI, with multimorbidity and poorer physical health contributing to health inequality. Screening tools could potentially assist the optimisation of medicines to protect the physical health of people with SMI. The aim of our research was to design and validate a medicines optimisation tool (OPTIMISE) to help clinicians to optimise physical health in people with SMI. METHODS: A review of existing published guidelines, PubMed and Medline was carried out. Literature was examined for medicines optimisation recommendations and also for reference to the management of physical illness in people with mental illness. Potential indicators were grouped according to physiological system. A multidisciplinary team with expertise in mental health and the development of screening tools agreed that 83 indicators should be included in the first draft of OPTIMISE. The Delphi consensus technique was used to develop and validate the contents. A 17-member multidisciplinary panel of experts from the UK and Ireland completed 2 rounds of Delphi consensus, rating their level of agreement to 83 prescribing indicators using a 5-point Likert scale. Indicators were accepted for inclusion in the OPTIMISE tool after achieving a median score of 1 or 2, where 1 indicated strongly agree and 2 indicated agree, and 75th centile value of ≤ 2. Interrater reliability was assessed among 4 clinicians across 20 datasets and the chance corrected level of agreement (kappa) was calculated. The kappa statistic was interpreted as poor if 0.2 or less, fair if 0.21-0.4, moderate if 0.41-0.6, substantial if 0.61-0.8, and good if 0.81-1.0. RESULTS: Consensus was achieved after 2 rounds of Delphi for 62 prescribing indicators where 53 indicators were accepted after round 1 and a further 9 indicators were accepted after round 2. Interrater reliability of OPTIMISE between physicians and pharmacists indicated a substantial level of agreement with a kappa statistic of 0.75. CONCLUSIONS: OPTIMISE is a 62 indicator medicines optimisation tool designed to assist decision making in those treating adults with SMI. It was developed using a Delphi consensus methodology and interrater reliability is substantial. OPTIMISE has the potential to improve medicines optimisation by ensuring preventative medicines are considered when clinically indicated. Further research involving the implementation of OPTIMISE is required to demonstrate its true benefit. TRIAL REGISTRATION: This article does not report the results of a health care intervention on human participants.

Development and proposed evaluation of an eHealth learning tool for undergraduate university students in Ireland.

Undergraduate university students are at a critical stage of development in terms of their academic, social, psychological and behavioural health. Patterns established during these formative years can last a lifetime. eHealth tools have the potential to be engaging, convenient and accessible to a wide range of students by providing health information and enhancing the uptake of positive health behaviours. The 'Healthy Trinity Online Tool' (H-TOT) was developed in collaboration with students and a transdisciplinary team with decades of experience between them in terms of research, clinical responsibility and service delivery. Developmental steps undertaken included: a literature review to formulate the topic content choices; a survey of students to check the relevance and suitability of topics identified; and, the tacit experience of the development team. This co-design model led to the development of content encompassing academic life, healthy eating, physical activity, mood, financial matters, alcohol, tobacco, drugs and relaxation. Qualitative focus groups were subsequently conducted for in-depth exploration of the usage and functionality of H-TOT. The theoretical underpinnings include the locus of control and social cognitive theory. Evidence-based behavioural change techniques are embedded throughout. During early pre-piloting of H-TOT, the team identified and solved content functionality problems. The tone of the content was also revised to ensure it was non-judgemental. To make the H-TOT as interactive as possible, video scenarios were included and all content was audio-recorded to allow playback for students with visual or learning difficulties. Evaluation plans for the pilot year of H-TOT are outlined.

Speech and Language Therapists' Perspectives of an E-Learning Course on Providing Feedback in the Clinical Learning Environment.

BACKGROUND: A fundamental component of supervising a student speech and language therapist (SLT) on placement is the provision of feedback. There are numerous identified challenges to ensure the delivery of high-quality feedback to optimise student learning and student success. Supervisors can help overcome these challenges and engage in evidence-based feedback processes if they are supported to develop the necessary knowledge and skills. E-learning is one possible means to provide this professional development to a large number of practising SLTs who are geographically dispersed and have conflicting schedules. AIMS: This study aimed to capture and evaluate the perspectives of SLTs who completed an e-learning course on providing feedback in the clinical learning environment, including the suitability and effectiveness of the e-learning tool used. METHODS AND PROCEDURES: An innovative e-learning course was designed to provide asynchronous video and interactive content on evidence-based theories and practices for effective feedback processes. Clinical scenarios relevant to the discipline of speech and language therapy were included. Participants were invited to complete optional, anonymous pre- and post-evaluation surveys. Data were analysed quantitively (descriptive and inferential statistics) and qualitatively (thematic analysis). OUTCOMES AND RESULTS: Participants indicated that the e-learning course supported them to enhance their feedback processes in the clinical learning environment through identified changes to their practices. The increases in confidence providing feedback they reported were statistically significant. In addition, the e-learning course was rated highly on numerous variables related to quality. Recommendations for adaptations and additions were also highlighted. CONCLUSIONS AND IMPLICATIONS: An e-learning course on effective and evidence-based feedback processes provides an opportunity to provide professional development to a large number of geographically dispersed practitioners in a cost-effective and flexible way. This could ensure more SLTs are confident and competent in their role as supervisor of students, which requires distinct knowledge and skills from that of a practitioner. Ultimately, this will help maximise educator and student success in the feedback process and consequently improve clinical performance and healthcare delivery.

Through the looking glass: the rabbit hole of reflective practice.

Reflective practice is a common feature of nurse education. Indeed, the development of nursing practice is associated with being a 'reflective practitioner'. However, how we see ourselves or interpret past events is often influenced by our own unconscious biases. While it is reasonable to hold favourable views of one's ability, biased or lack of self-insight might mean that one is actually unskilled and unaware of it. In the ambiguous clinical context where an act or omission can have potentially devastating consequences, the implications of this are significant. The questions of whether and how reflection addresses unconscious biases are relatively unexplored in the nursing literature. Given that accurate self-assessment is integral to reflective practice, this article attempts to explore the potential impact of unconscious bias on reflection. The authors conclude that while biases may limit our ability to learn from reflection, this is not a reason to dispense with reflective practice, but rather, is even more reason to critically engage with the process. Nurses of all levels must be encouraged to reflect on both their practice, and their reflection.

A Common Polymorphism in HIBCH Influences Methylmalonic Acid Concentrations in Blood Independently of Cobalamin.

Methylmalonic acid (MMA) is a by-product of propionic acid metabolism through the vitamin B12 (cobalamin)-dependent enzyme methylmalonyl CoA mutase. Elevated MMA concentrations are a hallmark of several inborn errors of metabolism and indicators of cobalamin deficiency in older persons. In a genome-wide analysis of 2,210 healthy young Irish adults (median age 22 years) we identified a strong association of plasma MMA with SNPs in 3-hydroxyisobutyryl-CoA hydrolase (HIBCH, p = 8.42 × 10(-89)) and acyl-CoA synthetase family member 3 (ACSF3, p = 3.48 × 10(-19)). These loci accounted for 12% of the variance in MMA concentration. The most strongly associated SNP (HIBCH rs291466; c:2T>C) causes a missense change of the initiator methionine codon (minor-allele frequency = 0.43) to threonine. Surprisingly, the resulting variant, p.Met1?, is associated with increased expression of HIBCH mRNA and encoded protein. These homozygotes had, on average, 46% higher MMA concentrations than methionine-encoding homozygotes in young adults with generally low MMA concentrations (0.17 [0.14-0.21] µmol/L; median [25(th)-75(th) quartile]). The association between MMA levels and HIBCH rs291466 was highly significant in a replication cohort of 1,481 older individuals (median age 79 years) with elevated plasma MMA concentrations (0.34 [0.24-0.51] µmol/L; p = 4.0 × 10(-26)). In a longitudinal study of 185 pregnant women and their newborns, the association of this SNP remained significant across the gestational trimesters and in newborns. HIBCH is unique to valine catabolism. Studies evaluating flux through the valine catabolic pathway in humans should account for these variants. Furthermore, this SNP could help resolve equivocal clinical tests where plasma MMA values have been used to diagnose cobalamin deficiency.

Lineage specific histories of Mycobacterium tuberculosis dispersal in Africa and Eurasia.

Mycobacterium tuberculosis (M.tb) is a globally distributed, obligate pathogen of humans that can be divided into seven clearly defined lineages. An emerging consensus places the origin and global dispersal of M.tb within the past 6,000 years: identifying how the ancestral clone of M.tb spread and differentiated within this timeframe is important for identifying the ecological drivers of the current pandemic. We used Bayesian phylogeographic inference to reconstruct the migratory history of M.tb in Africa and Eurasia and to investigate lineage specific patterns of spread from a geographically diverse sample of 552 M.tb genomes. Applying evolutionary rates inferred with ancient M.tb genome calibration, we estimated the timing of major events in the migratory history of the pathogen. Inferred timings contextualize M.tb dispersal within historical phenomena that altered patterns of connectivity throughout Africa and Eurasia: trans-Indian Ocean trade in spices and other goods, the Silk Road and its predecessors, the expansion of the Roman Empire, and the European Age of Exploration. We found that Eastern Africa and Southeast Asia have been critical in the dispersal of M.tb. Our results further reveal that M.tb populations have grown through range expansion, as well as in situ, and delineate the independent evolutionary trajectories of bacterial subpopulations underlying the current pandemic.

Supporting self-management of asthma through patient education.

Asthma affects people worldwide. In developed countries 1 in 12 individuals suffer from asthma, while in Ireland this ratio is closer to 1 in 10. Managing asthma symptoms and triggers reduces the potential exacerbation of asthmatic attacks. This article identifies the importance of asthma management, triggers, inhaler techniques and self-management for optimal health. Education by nurses and health professionals can make a significant contribution to asthma care and self-management. The purpose of patient education for self-management of asthma is twofold: to raise awareness of effective inhaler technique and to support self-management of asthma triggers for health and symptom control.

Diversity of Mycobacterium tuberculosis across Evolutionary Scales.

Tuberculosis (TB) is a global public health emergency. Increasingly drug resistant strains of Mycobacterium tuberculosis (M.tb) continue to emerge and spread, highlighting adaptability of this pathogen. Most studies of M.tb evolution have relied on 'between-host' samples, in which each person with TB is represented by a single M.tb isolate. However, individuals with TB commonly harbor populations of M.tb numbering in the billions. Here, we use analyses of M.tb genomic data from within and between hosts to gain insight into influences shaping genetic diversity of this pathogen. We find that the amount of M.tb genetic diversity harbored by individuals with TB can vary dramatically, likely as a function of disease severity. Surprisingly, we did not find an appreciable impact of TB treatment on M.tb diversity. In examining genomic data from M.tb samples within and between hosts with TB, we find that genes involved in the regulation, synthesis, and transportation of immunomodulatory cell envelope lipids appear repeatedly in the extremes of various statistical measures of diversity. Many of these genes have been identified as possible targets of selection in other studies employing different methods and data sets. Taken together, these observations suggest that M.tb cell envelope lipids are targets of selection within hosts. Many of these lipids are specific to pathogenic mycobacteria and, in some cases, human-pathogenic mycobacteria. We speculate that rapid adaptation of cell envelope lipids is facilitated by functional redundancy, flexibility in their metabolism, and their roles mediating interactions with the host.

In vitro blood cell responsiveness to IFN-α predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patients.

BACKGROUND: Treatment with interferon-alpha (IFN-α) and ribavirin successfully clears hepatitis C virus (HCV) infection in 50% of patients infected with genotype 1. Addition of NS3-4A protease inhibitors (PIs) increases response rates but results in additional side effects and significant economic costs. Here, we hypothesised that in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-α stimulation would identify patients who achieved sustained virological response (SVR) on dual therapy alone and thus not require addition of PIs. METHODS: PBMCs were isolated from HCV infected patients (n = 42), infected with either HCV genotype 1 or genotype 3, before commencing therapy and stimulated in vitro with IFN-α. Expression of the IFN stimulated genes (ISGs) PKR, OAS and MxA was measured and correlated with subsequent treatment response and IL28B genotype. RESULTS: Genotype 1 infected patients who achieved SVR had significantly higher pre-treatment expression of PKR (p = 0.0148), OAS (p = 0.0019) and MxA (p = 0.0019) in IFN-α stimulated PBMCs, compared to genotype 1 infected patients who did not achieve SVR or patients infected with genotype 3, whose in vitro ISG expression did not correlate with clinical responsiveness. IL28B genotype (rs12979860) did not correlate with endogenous or IFN-α stimulated ISG responsiveness. CONCLUSIONS: In vitro responsiveness of PBMCs to IFN-α from genotype 1 infected patients predicts clinical responsiveness to dual therapy, independently of IL28B genotype. These results indicate that this sub-group of HCV infected patients could be identified pre-treatment and successfully treated without PIs, thus reducing adverse side effects and emergence of PI resistant virus while making significant economic savings.

Plasmons Enhancing Sub-Bandgap Photoconductivity in TiO2 Nanoparticles Film.

The coupling between sub-bandgap defect states and surface plasmon resonances in Au nanoparticles and its effects on the photoconductivity performance of TiO2 are investigated in both the ultraviolet (UV) and visible spectrum. Incorporating a 2 nm gold nanoparticle layer in the photodetector device architecture creates additional trapping pathways, resulting in a faster current decay under UV illumination and a significant enhancement in the visible photocurrent of TiO2, with an 8-fold enhancement of the defects-related photocurrent. We show that hot electron injection (HEI) and plasmonic resonance energy transfer (PRET) jointly contribute to the observed photoconductivity enhancement. In addition to shedding light on the below-band-edge photoconductivity of TiO2, our work provides insight into new methods to probe and examine the surface defects of metal oxide semiconductors using plasmonic resonances.

Challenging gestational trophoblastic disease cases and mimics: An exemplar for the management of rare tumours.

OBJECTIVE: Rare tumour management is challenging for clinicians as evidence bases are limited and clinical trials are difficult to conduct. It is even more difficult for patients where self-reliance alone is insufficient to overcome the challenges of navigating care which is often poorly evidence based. In Ireland, a national Gestational Trophoblastic Disease (GTD) service was established as one of 3 initiatives for rare tumours by the National Cancer Control Programme. The service has a national clinical lead, a dedicated supportive nursing service and a clinical biochemistry liaison team. This study sought to assess the impact of a GTD centre using national clinical guidelines and integrating and networking with European and International GTD groups on the clinical management of challenging GTD cases and to consider the application of this model of care to other rare tumour management. STUDY DESIGN: In this article, we analyse the impact of a national GTD service on five challenging cases, and review how the service affects patient management in this rare tumour type. These cases were selected from a cohort of patients who were voluntarily registered in the service based on the diagnostic management dilemma they posed. RESULTS: Case management was impacted by the identification of GTD mimics, the provision of lifesaving treatment of metastatic choriocarcinoma with brain metastasis, networking with international colleagues, the identification of early relapse, the use of genetics to differentiate treatment pathways and prognosis, and supportive supervision of treatment courses of up to 2 years of therapy in a cohort of patients starting or completing families. CONCLUSION: The National GTD service could be an exemplar for the management of rare tumours (such as cholangiocarcinoma) in our jurisdiction which could benefit from a similar constellation of supports. Our study demonstrates the importance of a nominated national clinical lead, dedicated nurse navigator support, registration of cases and networking. The impact of our service would be greater if registration was mandatory rather than voluntary. Such a measure would also ensure equity of access for patients to the service, assist in quantifying the need for resourcing and facilitate research to improve outcomes.

Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) occurs due to alteration of the microbiota within the upper gastrointestinal tract. Proton pump inhibitor (PPI) therapy has been suggested as a risk factor for SIBO; however, the published reports have yielded conflicting results on the association between PPI therapy and risk of developing SIBO. The aim of this study was to compare the prevalence of SIBO as measured by glucose hydrogen breath testing (GHBT) in patients on PPI therapy compared with those not on PPI therapy. METHODS: A retrospective chart review was completed for all patients who underwent GHBT testing from 2004 to 2010. Breath samples for hydrogen (H2) and methane (CH4) were collected before and every 20 min for 120 min following ingestion of a 50-g oral glucose load. We used the following criteria to define a positive GHBT (a) increase in H2 > 20 parts per million (p.p.m.) over baseline, (b) sustained rise H2 > 10 p.p.m. over baseline, (c) CH4 > 15 p.p.m. over baseline, and (d) either rise H2 > 20 p.p.m. over baseline or CH4 > 15 p.p.m. RESULTS: A total of 1,191 patients (70% female) were included, of whom 566 (48%) were on PPI therapy. GHBT positivity did not differ significantly between PPI users and nonusers by any of the diagnostic criteria used and PPI use was not significantly associated with GHBT positivity using any of these criteria. GHBT positivity was associated with older age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.04) and antidiarrheal use (OR 1.99, 95% CI 1.15-3.44) using H2 > 20, older age (OR 1.01, 95% CI 1.00-1.02) and diarrhea (OR 1.53, 95% CI 1.13-2.09) using H2 > 10, and older age (OR 1.01, 95% CI 1.00-1.02) using either H2 > 20 or CH4 > 15. PPI use was not significantly associated with GHBT positivity using any of these criteria. CONCLUSIONS: In this large, adequately powered equivalence study, PPI use was not found to be significantly associated with the presence of SIBO as determined by the GHBT.

A hydrological simulation dataset of the Upper Colorado River Basin from 1983 to 2019.

This article presents a hydrological reconstruction of the Upper Colorado River Basin with an hourly temporal resolution, and 1-km spatial resolution from October 1982 to September 2019. The validated dataset includes a suite of hydrologic variables including streamflow, water table depth, snow water equivalent (SWE) and evapotranspiration (ET) simulated by an integrated hydrological model, ParFlow-CLM. The dataset was validated over the period with a combination of point observations and remotely sensed products. These datasets provide a long-term, natural-flow, simulation for one of the most over-allocated basins in the world.

Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here, we used M. tb experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation. We identified novel candidate loci, adding to our understanding of the genetic architecture underlying M. tb biofilm development. Under selective pressure to grow as a biofilm, regulatory mutations rapidly swept to fixation and were associated with changes in multiple traits, including extracellular matrix production, cell size, and growth rate. Genetic and phenotypic paths to enhanced biofilm growth varied according to the genetic background of the parent strain, suggesting that epistatic interactions are important in M. tb adaptation to changing environments.

In many environments, bacteria live together in structures called biofilms. Cells in biofilms coordinate with each other to protect the group and allow it to survive difficult conditions. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, forms biofilms when it infects the human body. Biofilms make the infection a lot more difficult to treat, which may be one of the reasons why tuberculosis is the deadliest bacterial infection in the world. Bacteria evolve rapidly over the course of a single infection, but bacteria forming biofilms evolve differently to bacteria living alone. This evolution happens through mutations to the bacterial DNA, which can be small (a single base in a DNA sequence changes to a different base) or larger changes (such as the deletion or insertion of several bases). Smith, Youngblom et al. studied the evolution of tuberculosis growing in biofilms in the lab. As the bacteria evolved, they tended to form thicker biofilms, an effect linked to 14 mutations involving single base DNA changes and four larger ones. Most of the changes were in regulatory regions of DNA, which control whether genes are 'read' by cells to produce proteins. These regions often change more though evolution than regions coding for proteins, because they have a coordinated effect on a group of related genes rather than randomly altering individual genes. Smith, Youngblom et al. also showed that biofilms made from different strains of tuberculosis evolved in different ways. Smith Youngblom et al.'s findings provide more information regarding how bacteria adapt to living in biofilms, which may reveal new ways to control them. This could have applications in water treatment, food production and healthcare. Learning how to treat bacteria growing in biofilms could also improve the outcomes for patients infected with tuberculosis.

Enhancing Existing Formal Home Care to Improve and Maintain Functional Status in Older Adults: Results of a Feasibility Study on the Implementation of Care to Move (CTM) in an Irish Healthcare Setting.

Background: Care to Move (CTM) provides a series of consistent 'movement prompts' to embed into existing movements of daily living. We explored the feasibility of incorporating CTM approaches in home care settings. Methods: Feasibility study of the CTM approach in older adults receiving home care. Recruitment, retention and attrition (three time points), adherence, costs to deliver and data loss analyzed and differentiated pre and post the COVID-19 pandemic. Secondary outcomes, including functional status, physical activity, balance confidence, quality of life, cost to implement CTM. Results: Fifty-five home care clients (69.6% of eligible sample) participated. Twenty were unable to start due to COVID-19 disruptions and health issues, leaving 35 clients recruited, mostly women (85.7%), mean age 82.8 years. COVID-19 disruption impacted on the study, there was 60% retention to T2 assessments (8-weeks) and 13 of 35 (37.1%) completed T3 assessments (6-months). There were improvements with small to medium effect sizes in quality of life, physical function, balance confidence and self-efficacy. Managers were supportive of the roll-out of CTM. The implementation cost was estimated at EUR 280 per carer and annual running costs at EUR 75 per carer. Conclusion: Embedding CTM within home support services is acceptable and feasible. Data gathered can power a definitive trial.

Topic update: effects of colorectal cancer treatments on female fertility and potential methods for fertility preservation.

PURPOSE: Preservation of fertility in young females with a diagnosis of colorectal cancer is gaining increasing importance as survival rates of cancer increase. This review examines the effects of pelvic surgery, chemotherapy, and radiotherapy on fecundity. It also discusses the options available to patients including ovarian transposition, gonadotropin-releasing hormone analogs, embryo and ovarian cryopreservation, and ovarian tissue transplantation. METHODS: A search of MEDLINE, EMBASE, and the Cochrane library was performed using keywords and exploded Mesh search headings and the subsequent articles were reviewed. Relevant studies were included. RESULTS: There are no studies that examine the effect of surgery for colorectal cancer on female fertility, in particular, surgery below the peritoneal reflection for rectal cancer. However, patients with familial adenomatous polyposis have a similar fecundity before and after proctocolectomy with ileal pouch-anal anastomosis. These patients did significantly better than patients with ulcerative colitis who underwent the same procedure. There is conflicting evidence regarding the effects of open vs laparoscopic surgery on fertility. Oxaliplatin, an adjuvant therapy, has moderate gonadotoxic effects. Fluorouracil is considered to have almost no effect on human reproductive function. Gonadotropin-releasing hormone agonists are currently used to preserve female fecundity during chemotherapy. A recent update of patients treated for Hodgkin lymphoma showed that significantly fewer women treated with a gonadotropin-releasing hormone agonist during chemotherapy exhibited premature ovarian failure. Ovarian transposition reduces the radiation dose to approximately 5% to 10% of the dose to the ovaries in their normal position. Other options are available to women with cancer who wish to preserve their germ line, including embryo and oocyte cryopreservation and ovarian tissue cryopreservation. CONCLUSION: Significant advances are now allowing females to preserve their fertility after cancer treatment. It is essential that patients receive adequate fertility counseling before any intervention to give them an opportunity to consider fertility alternatives.

Evaluation of an eLearning teaching innovation to assist clinical radiation therapy educators in the provision of student feedback.

BACKGROUND: Clinical placement is an integral part of the Radiation Therapy undergraduate programme. Feedback and formative assessment during clinical placement are regarded as key to developing clinical skills and competencies. Students regularly report dissatisfaction with the feedback process while clinical educators report heavy clinical workloads and a lack of guidance on feedback mechanisms as barriers to providing meaningful student feedback. METHODS: An eLearning teaching intervention was developed to support radiation therapists in the provision of student feedback in the clinic. Thematic analysis was used to report attitudes to feedback and feedback practices collected in a pre and a post intervention evaluation. RESULTS: 30 radiation therapists completed the module and pre and post intervention evaluations. Prior to taking the module just over half of respondents stated that they offered regular and on-going feedback throughout the student's placement. Positive attitudes to feedback were reported. Following completion of the eLearning tool respondents reported a higher level of confidence in the provision of student feedback and almost 70% said the module had changed how they would approach the feedback process by using feedback models in the future. DISCUSSION: Good and timely feedback is essential and allows a student opportunity to improve prior to the end of the placement. It also teaches students how to self-assess and self-reflect - skills that they can use in continuous professional development after they graduate. Radiation therapists appreciate the structure that using a model in the feedback process offers. CONCLUSION: This eLearning teaching intervention was received favourably by radiation therapists who are key to creating a culture of feedback in the clinical environment that will facilitate students in becoming competent healthcare professionals.