Publications by authors named "Sarah Sims"

43 Publications

is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease.

Eur Respir J 2021 Sep 29. Epub 2021 Sep 29.

Laboratory of Pharmaceutical Microbiology, Ghent University, Gent, Belgium

Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognized, the influence of other microbiota members is still poorly understood. Here, we show that , a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- and LPS-induced pro-inflammatory responses, both (3-D cell culture model) and (mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance of spp. was negatively correlated with pro-inflammatory markers (IL-8, IL-1β) and matrix metalloproteinases (MMP-1, MMP-8 and MMP-9) in sputum. Mechanistic studies revealed that inhibits NF-κB pathway activation by reducing the phosphorylation of IκB-α and consequently the expression of NF-κB target genes. These findings indicate that the presence of in the lower airways potentially mitigates inflammation, which could in turn influence severity and progression of chronic respiratory disorders.
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http://dx.doi.org/10.1183/13993003.01293-2021DOI Listing
September 2021

Prevention of SARS-CoV-2 (COVID-19) transmission in residential aged care using ultraviolet light (PETRA): a two-arm crossover randomised controlled trial protocol.

BMC Infect Dis 2021 Sep 17;21(1):967. Epub 2021 Sep 17.

The South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia.

Background: SARS-CoV-2 poses a considerable threat to those living in residential aged care facilities (RACF). RACF COVID-19 outbreaks have been characterised by the rapid spread of infection and high rates of severe disease and associated mortality. Despite a growing body of evidence supporting airborne transmission of SARS-CoV-2, current infection control measures in RACF including hand hygiene, social distancing, and sterilisation of surfaces, focus on contact and droplet transmission. Germicidal ultraviolet (GUV) light has been used widely to prevent airborne pathogen transmission. Our aim is to investigate the efficacy of GUV technology in reducing the risk of SARS-CoV-2 infection in RACF.

Methods: A multicentre, two-arm double-crossover, randomised controlled trial will be conducted to determine the efficacy of GUV devices to reduce respiratory viral transmission in RACF, as an adjunct to existing infection control measures. The study will be conducted in partnership with three aged care providers in metropolitan and regional South Australia. RACF will be separated into paired within-site zones, then randomised to intervention order (GUV or control). The initial 6-week period will be followed by a 2-week washout before crossover to the second 6-week period. After accounting for estimated within-zone and within-facility correlations of infection, and baseline infection rates (10 per 100 person-days), a sample size of n = 8 zones (n = 40 residents/zone) will provide 89% power to detect a 50% reduction in symptomatic infection rate. The primary outcome will be the incidence rate ratio of combined symptomatic respiratory infections for intervention versus control. Secondary outcomes include incidence rates of hospitalisation for complications associated with respiratory infection; respiratory virus detection in facility air and fomite samples; rates of laboratory confirmed respiratory illnesses and genomic characteristics.

Discussion: Measures that can be deployed rapidly into RACF, that avoid the requirement for changes in resident and staff behaviour, and that are effective in reducing the risk of airborne SARS-CoV-2 transmission, would provide considerable benefit in safeguarding a highly vulnerable population. In addition, such measures might substantially reduce rates of other respiratory viruses, which contribute considerably to resident morbidity and mortality. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12621000567820 (registered on 14th May, 2021).
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http://dx.doi.org/10.1186/s12879-021-06659-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446719PMC
September 2021

Protecting older people living in care homes from COVID-19: a protocol for a mixed-methods study to understand the challenges and solutions to implementing social distancing and isolation.

BMJ Open 2021 08 4;11(8):e050706. Epub 2021 Aug 4.

Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK.

Introduction: Older people living in residential and nursing care homes often have complex needs and are at high risk of poor health outcomes and mortality, especially if they contract COVID-19. Care homes use infection prevention and control measures such as social distancing and isolating residents to protect them from COVID-19. The care home sector has stated that implementing social distancing and isolation when caring for residents is a significant challenge. This paper presents the protocol of a mixed-methods study to explore and understand the real-life experiences of implementing social distancing and isolation of residents in care homes for older people from the perspective of residents, families/friends and staff working in and with care homes. The study aims to develop a toolkit of resources for health and care delivery now and for future outbreaks of infectious diseases.

Methods And Analysis: The study will be conducted in three phases. Phase 1 is a rapid review of evidence to collate knowledge on the mechanisms and measures used by care homes and long-term facilities to socially distance and isolate older people or control the spread of other infectious and contagious diseases. The review results will contribute to participant interviews in phase 2 and toolkit development in phase 3. Phase 2 will involve case studies with six care homes in England, involving the conduct of individual interviews with residents, families and friends, and staff, collection of care home policies and protocols related to social distancing and isolation for residents, and routinely collected care home data. A focus group with a purposive sample of external key informants will also be conducted. Phase 3, synthesising findings from phases 1 and 2, will inform the codesign of a toolkit of resources for residents, families/friends and care homes.

Ethics And Dissemination: The study has been approved by Coventry and Warwick Research Ethics Committee (20/WM/0318). To maximise impact, we will work closely with the Study Committees and the Patient and Public Involvement group to ensure the findings reach key stakeholders, including residents, families/friends, care homes, commissioners and organisations representing care home providers. We will disseminate the study outputs in peer-reviewed and professional journals, at professional conferences and via other knowledge transfer activities with the care home sector, and resident and carer organisations. The toolkit comprising evidence-informed guidance and resources and a mosaic film will be hosted on a project webpage.

Registration Details: This project is funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research Programme (Project reference NIHR132541). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Prospero Registration Number: CRD42021226734.
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http://dx.doi.org/10.1136/bmjopen-2021-050706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342044PMC
August 2021

Visual Analytics Dashboard Promises to Improve Hypertension Guideline Implementation.

Am J Hypertens 2021 May 27. Epub 2021 May 27.

Department of Internal Medicine, Henry Ford Hospital and Wayne State University, Detroit, MI, United States.

Background: Primary care management of hypertension under new guidelines incorporates assessment of cardiovascular disease risk and commonly requires review of electronic health record (EHR) data. Visual analytics can streamline the review of complex data and may lessen the burden clinicians face using the EHR. This study sought to assess the utility of a visual analytics dashboard in addition to EHR in managing hypertension in a primary care setting.

Methods: Primary care physicians within an urban, academic internal medicine clinic were tasked with performing two simulated patient encounters for HTN management: the first using standard EHR, and the second using EHR paired with a visual dashboard. The dashboard included graphical blood pressure trends with guideline-directed targets, calculated ASCVD risk score, and relevant medications. Guideline-appropriate antihypertensive prescribing, correct target blood pressure goal, and total encounter time were assessed.

Results: We evaluated 70 case simulations. Use of the dashboard with the EHR compared to use of the EHR alone was associated with greater adherence to prescribing guidelines (95% vs. 62%, p<0.001) and more correct identification of BP target (95% vs. 57%, p<0.01). Total encounter time fell an average of 121 seconds (95% CI 69 - 157 seconds, p<0.001) in encounters that used the dashboard combined with the EHR.

Conclusions: The integration of a hypertension-specific visual analytics dashboard with EHR demonstrates the potential to reduce time and improve hypertension guideline implementation. Further widespread testing in clinical practice is warranted.
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http://dx.doi.org/10.1093/ajh/hpab081DOI Listing
May 2021

Conventional myelosuppressive chemotherapy for non-haematological malignancy disrupts the intestinal microbiome.

BMC Cancer 2021 May 22;21(1):591. Epub 2021 May 22.

South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

Background: The gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown.

Methods: Faecal samples from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7-12 days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota diversity and composition was determined by 16S rRNA gene amplicon sequencing.

Results: Compared to pre-chemotherapy samples, samples collected 7-12 days following chemotherapy exhibited increased richness (mean 120 observed species ± SD 38 vs 134 ± 40; p = 0.007) and diversity (Shannon diversity: mean 6.4 ± 0.43 vs 6.6 ± 0.41; p = 0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11]; p = 0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13]; p = 0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03]; p = 0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle.

Conclusions: Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.
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http://dx.doi.org/10.1186/s12885-021-08296-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141218PMC
May 2021

A Spatiotemporal Tool to Project Hospital Critical Care Capacity and Mortality From COVID-19 in US Counties.

Am J Public Health 2021 06 15;111(6):1113-1122. Epub 2021 Apr 15.

Alexis Zebrowski and Brendan G. Carr are with the Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. Andrew Rundle, Tonguc Yaman, Wan Yang, James W. Quinn, and Charles C. Branas are with the Department of Epidemiology, Mailman School of Public Health, Columbia University, New York. Sen Pei and Jeffrey Shaman are with the Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University. Sarah Sims is with Patient Insight, Santa Monica, CA. Ronan Doorley is with Media Lab at the Massachusetts Institute of Technology, Cambridge. Neil Schluger is with the Division of Pulmonary, Allergy, and Critical Care Medicine, and Departments of Epidemiology and Environmental Health Sciences, Columbia University Irving Medical Center, Columbia University.

To create a tool to rapidly determine where pandemic demand for critical care overwhelms county-level surge capacity and to compare public health and medical responses. In March 2020, COVID-19 cases requiring critical care were estimated using an adaptive metapopulation SEIR (susceptible‒exposed‒infectious‒recovered) model for all 3142 US counties for future 21-day and 42-day periods from April 2, 2020, to May 13, 2020, in 4 reactive patterns of contact reduction-0%, 20%, 30%, and 40%-and 4 surge response scenarios-very low, low, medium, and high. In areas with increased demand, surge response measures could avert 104 120 additional deaths-55% through high clearance of critical care beds and 45% through measures such as greater ventilator access. The percentages of lives saved from high levels of contact reduction were 1.9 to 4.2 times greater than high levels of hospital surge response. Differences in projected versus actual COVID-19 demands were reasonably small over time. Nonpharmaceutical public health interventions had greater impact in minimizing preventable deaths during the pandemic than did hospital critical care surge response. Ready-to-go spatiotemporal supply and demand data visualization and analytics tools should be advanced for future preparedness and all-hazards disaster response.
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http://dx.doi.org/10.2105/AJPH.2021.306220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101594PMC
June 2021

The cystic fibrosis gut as a potential source of multidrug resistant pathogens.

J Cyst Fibros 2021 05 26;20(3):413-420. Epub 2020 Nov 26.

SAHMRI Microbiome Research Laboratory, Flinders University College of Medicine and Public Health, Adelaide, SA, Australia; Microbiome and Host Health, South Australia Health and Medical Research Institute, North Terrace, Adelaide, SA, Australia.

Background: The emergence of multidrug resistant (MDR) pathogens represents a profound threat to global health. Individuals with CF have amongst the highest cumulative antibiotic exposure of any patient group, including to critically-important last-line agents. While there is little evidence that antibiotic resistance in airway pathogens results in worse clinical outcomes for CF patients, the potential emergence of MDR pathogens in non-respiratory systems, as a consequence of CF care, represents a potential health threat to the wider population, including family and carers.

Methods: Stool from 19 adults with CF and 16 healthy adult controls was subjected to metagenomic sequencing, to assess faecal resistome, and culture-based analysis. Resistant isolates were identified phenotypically, and genetic determinants of resistance characterised by whole genome sequencing.

Results: CF and control faecal resistomes differed significantly (P = 0.0003). The proportion of reads that mapped to mobile genetic elements was significantly higher in CF (P = 0.014) and the composition was significantly different (P = 0.0001). Notably, CF patients displayed higher carriage of plasmid-mediated aminoglycoside-modifying genes ant(6)-Ib, aac(6')-Ip, and aph(3')-IIIa (P < 0.01). Culture-based analysis supported higher aminoglycoside resistance, with a higher proportion of aminoglycoside-resistant, Gram-negative bacteria (P < 0.0001). Isolated extended spectrum beta lactamase (ESBL)-positive Escherichia coli from CF stool exhibited phenotypic resistance to tobramycin and gentamicin. Genomic analysis showed co-localisation of both aminoglycoside resistance and ESBL genes, consistent with MDR emergence through horizontal gene transfer.

Conclusions: The carriage of potentially transmissible resistance within the adult CF gut microbiome is considerably greater than in healthy individuals and could contribute to the emergence and dissemination of MDR pathogens.
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http://dx.doi.org/10.1016/j.jcf.2020.11.009DOI Listing
May 2021

Understanding key mechanisms of successfully leading integrated team-based services in health and social care: protocol for a realist synthesis.

BMJ Open 2020 07 9;10(7):e038591. Epub 2020 Jul 9.

NIHR Health & Social Care Workforce Research Unit, King's College London, London, UK.

Introduction: As systems of health and social care in England move towards more integrated and collaborative models, leaders will need different skills than their predecessors to enable system leadership, building partnerships and working across organisations and sectors. There is little understanding of what the mechanisms for effective leadership across integrated health and social care systems might be, the contexts that influence good leadership, or the nature of the resulting outcomes. This review aims to identify, refine and test programme theories of leadership of integrated team-based services in health and social care, exploring what works, for whom and in what circumstances.

Methods And Analysis: This study uses a realist synthesis approach, following RAMESES guidelines, supported by stakeholder consultation. Stage 1 will develop initial programme theories about leadership of integrated health and social care based on a review of the scientific and grey literature and a stakeholder consultation workshop. Stage 2 will involve focused searching of empirical literature, data extraction and synthesis to refine the initial programme theories and identify relationships between identified contexts, mechanisms and outcomes. A second stakeholder event will guide the focus of the review. Stage 3 will further refine and interrogate the theories testing them against substantive theory on leadership of complex systems and through the experiences and expertise of the stakeholder group.

Ethics And Dissemination: Our study does not require ethics committee approval. This research will contribute to building an in-depth understanding of what aspects of leadership of integrated team-based services work, for whom and in what circumstances. It will identify the professional development needs of leaders and provide recommendations about optimal organisational and interorganisational structures and processes that support effective leadership in integrated health and social care systems. Findings will be disseminated through peer-reviewed journal publications, conference presentations and formal and informal reports.

Prospero Registration Number: CRD42018119291.
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http://dx.doi.org/10.1136/bmjopen-2020-038591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351270PMC
July 2020

The delivery of compassionate nursing care in a tick-box culture: Qualitative perspectives from a realist evaluation of intentional rounding.

Int J Nurs Stud 2020 Jul 20;107:103580. Epub 2020 Mar 20.

Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK. Electronic address:

Background: Compassion is integral to professional nursing practice worldwide and a fundamental value in healthcare. Following serious care failures at a healthcare provider in the United Kingdom, a government commissioned report (the Francis Report) made several recommendations for strengthening compassion in nursing care and consequently 'intentional rounding' was incorporated into nursing practice in the United Kingdom. Intentional rounding is a structured process implemented primarily in the United Kingdom, North America and Australia, whereby nurses conduct 1-2 hourly checks on every patient using a standardised protocol and documentation.

Objectives: To examine the role of intentional rounding in the delivery of compassionate nursing care in England from multiple perspectives.

Methods: This paper reports qualitative findings from one phase of a realist evaluation of intentional rounding which used a mixed-methods approach. Individual, semi-structured interviews were undertaken with 33 nursing staff, 17 senior nurse managers, 34 patients and 28 family carers from three geographically spread case study hospital sites in England. Interviews elicited detailed reflections on the contexts, mechanisms and outcomes of intentional rounding and how it impacted the interviewee and those around them.

Results: This study found little evidence that intentional rounding ensures the comfort, safety or dignity of patients or increases the delivery of compassionate care. The systematised approach of intentional rounding emphasises transactional care delivery in the utilisation of prescribed methods of recording or tick boxes rather than relational, individualised patient care. It has the potential to reduce the scope of nursing care to a minimum standard, leading to a focus on the fundamentals as well as the prevention of adverse events. Its documentation is primarily valued by nursing staff as a means of protecting themselves through written proof or 'evidence' of care delivered, rather than as a means of increasing compassionate care.

Conclusions: This large-scale, theoretically-driven study of intentional rounding - the first of its kind - demonstrates that intentional rounding prioritises data collection through tick boxes or a prescriptive and structured recording of care. Thus, intentional rounding neither improves the delivery of compassionate nursing care nor addresses the policy imperative it was intended to target. This study raises questions about the role, contribution and outcomes from intentional rounding and suggests a need for a wider, international debate within the nursing profession about its future use. If an intervention to increase compassionate nursing care is required, it may be better to start afresh, rather than attempting to adapt the system currently implemented.
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http://dx.doi.org/10.1016/j.ijnurstu.2020.103580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322536PMC
July 2020

The Effect of Sanitizers on Microbial Levels of Chicken Meat Collected from Commercial Processing Plants.

Int J Environ Res Public Health 2019 11 29;16(23). Epub 2019 Nov 29.

Primary Industries and Regions, Adelaide 5065, Australia.

Chicken meat can potentially become contaminated with bacteria at the processing plant. In Australia, there is currently a lack of knowledge on the parameters and indications of use of non-chlorine based treatments in the chicken meat processing plants. Chlorine is widely used as a sanitizer in Australian chicken meat processing plants but due to occupational health and safety concerns and consumer perception, there is a need to identify alternative sanitizers. This study aimed to assess the efficacy of four different sanitizers in reducing the microbial load from naturally contaminated chicken meat carcasses collected from the processing plants in South Australia. There was a significant variation in a load of and total viable count (TVC) between samples collected from two different processing plants and within carcass batches collected from the same plant that was tested during the study. All sanitizers generally reduced the load of on chicken meat carcasses. Treatment with acidified sodium chlorite significantly reduced the level of Salmonella enterica serovars at all temperatures tested during this study. These findings are helpful to the industry for selection of the appropriate sanitizers. Findings are also useful for the regulatory authorities in Australia for providing approval for the use of sanitizers.
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http://dx.doi.org/10.3390/ijerph16234807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926933PMC
November 2019

Realist synthesis of intentional rounding in hospital wards: exploring the evidence of what works, for whom, in what circumstances and why.

BMJ Qual Saf 2018 09 14;27(9):743-757. Epub 2018 Mar 14.

Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK.

Background: Intentional rounding (IR) is a structured process whereby nurses conduct one to two hourly checks with every patient using a standardised protocol.

Objective: A realist synthesis of the evidence on IR was undertaken to develop IR programme theories of what works, for whom, in what circumstances and why.

Methods: A three-stage literature search and a stakeholder consultation event was completed. A variety of sources were searched, including AMED, CINAHL, MEDLINE, PsycINFO, HMIC, Google and Google Scholar, for published and unpublished literature. In line with realist synthesis methodology, each study's 'fitness for purpose' was assessed by considering its relevance and rigour.

Results: A total of 44 papers met the inclusion criteria. To make the programme theories underpinning IR explicit, we identified eight a priori propositions: (1) when implemented in a comprehensive and consistent way, IR improves healthcare quality and satisfaction, and reduces potential harms; (2) embedding IR into daily routine practice gives nurses 'allocated time to care'; (3) documenting IR checks increases accountability and raises fundamental standards of care; (4) when workload and staffing levels permit, more frequent nurse-patient contact improves relationships and increases awareness of patient comfort and safety needs; (5) increasing time when nurses are in the direct vicinity of patients promotes vigilance, provides reassurance and reduces potential harms; (6) more frequent nurse-patient contact enables nurses to anticipate patient needs and take pre-emptive action; (7) IR documentation facilitates teamwork and communication; and (8) IR empowers patients to ask for what they need to maintain their comfort and well-being. Given the limited evidence base, further research is needed to test and further refine these propositions.

Conclusions: Despite widespread use of IR, this paper highlights the paradox that there is ambiguity surrounding its purpose and limited evidence of how it works in practice.
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http://dx.doi.org/10.1136/bmjqs-2017-006757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109250PMC
September 2018

Moringa oleifera functionalised sand - reuse with non-ionic surfactant dodecyl glucoside.

J Water Health 2017 Oct;15(6):863-872

School of Chemical Engineering, The University of Adelaide, Adelaide 5005, Australia E-mail:

Moringa oleifera seeds are well known for their ability to cause flocculation in turbid water and facilitate bacterial inhibition. These effects are due to the cationic polypeptide MO, which affects the surface charge of suspended particles and causes lysis of bacterial cells. However, the attachment of bacteria to MO prevents further bacterial attachment, reducing the effectiveness of the seeds. This research investigated the effect of surfactants on functionality and reuse of Moringa seeds to develop a sustainable water treatment technique. The seed extracts (MO) were used with a functionalised sand system, and the sands were exposed to commercially available (ionic and non-ionic) surfactants, dodecyl glucoside and sodium dodecyl sulfate. Artificially polluted water contaminated with Escherichia coli was used to evaluate the efficiency of the system. The non-ionic surfactant was found to be effective at separating E. coli from the functionalised sand without the detachment of the MO and subsequent loss of the system efficiency. This was successfully repeated four times. The results demonstrated a sustainable, reusable technique to inhibit bacterial contamination in water.
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http://dx.doi.org/10.2166/wh.2017.241DOI Listing
October 2017

Evaluation of robenidine analog NCL195 as a novel broad-spectrum antibacterial agent.

PLoS One 2017 5;12(9):e0183457. Epub 2017 Sep 5.

Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia.

The spread of multidrug resistance among bacterial pathogens poses a serious threat to public health worldwide. Recent approaches towards combating antimicrobial resistance include repurposing old compounds with known safety and development pathways as new antibacterial classes with novel mechanisms of action. Here we show that an analog of the anticoccidial drug robenidine (4,6-bis(2-((E)-4-methylbenzylidene)hydrazinyl)pyrimidin-2-amine; NCL195) displays potent bactericidal activity against Streptococcus pneumoniae and Staphylococcus aureus by disrupting the cell membrane potential. NCL195 was less cytotoxic to mammalian cell lines than the parent compound, showed low metabolic degradation rates by human and mouse liver microsomes, and exhibited high plasma concentration and low plasma clearance rates in mice. NCL195 was bactericidal against Acinetobacter spp and Neisseria meningitidis and also demonstrated potent activity against A. baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. in the presence of sub-inhibitory concentrations of ethylenediaminetetraacetic acid (EDTA) and polymyxin B. These findings demonstrate that NCL195 represents a new chemical lead for further medicinal chemistry and pharmaceutical development to enhance potency, solubility and selectivity against serious bacterial pathogens.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183457PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584945PMC
October 2017

What aspects of intentional rounding work in hospital wards, for whom and in what circumstances? A realist evaluation protocol.

BMJ Open 2017 01 9;7(1):e014776. Epub 2017 Jan 9.

Faculty of Health, Social Care and Education, Kingston University and St George's, University of London, London, UK.

Introduction: Intentional rounding (IR) is a structured process whereby nurses in hospitals carry out regular checks, usually hourly, with individual patients using a standardised protocol to address issues of positioning, pain, personal needs and placement of items. The widespread implementation of IR across the UK has been driven by the recommendations of the Francis Inquiry although empirical evidence of its effectiveness is poor. This paper presents a protocol of a multimethod study using a realist evaluation approach to investigate the impact and effectiveness of IR in hospital wards on the organisation, delivery and experience of care from the perspective of patients, their family members and staff.

Methods And Analysis: The study will be conducted in four phases. Phase 1: theory development using realist synthesis to generate hypotheses about what the mechanisms of IR may be, what particular groups may benefit most or least and what contextual factors might be important to its success or failure which will be tested in subsequent phases of the study. Phase 2: a national survey of all NHS acute trusts to explore how IR is implemented and supported across England. Phase 3: case studies to explore how IR is implemented 'on the ground', including individual interviews with patients, family members and staff, non-participant observation, retrieval of routinely collected patient outcomes and cost analysis. Phase 4: accumulative data analysis across the phases to scrutinise data for patterns of congruence and discordance and develop an overall evaluation of what aspects of IR work, for whom and in what circumstances.

Ethics And Dissemination: The study has been approved by NHS South East Coast-Surrey Research Ethics Committee. Findings will be published in a wide range of outputs targeted at key audiences, including patient and carer organisations, nursing staff and healthcare managers.
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http://dx.doi.org/10.1136/bmjopen-2016-014776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223681PMC
January 2017

Impact of 12h shift patterns in nursing: a scoping review.

Int J Nurs Stud 2015 Feb 1;52(2):605-34. Epub 2014 Nov 1.

United Kingston University and St. George's, University of London, United Kingdom.

Objectives: To provide a comprehensive scoping review of evidence of the impact and effectiveness of 12h shifts in the international nursing literature, supplemented by a review of evidence in other, non-nursing related industries.

Data Sources: A search of the academic literature was undertaken in electronic databases (AMED, MEDLINE, CINAHL, PsychInfo, Scopus, HMIC, the Cochrane Library, Business Source Premier, Econ Lit, ASSIA and Social Policy and Practice).

Review Methods: A total of 158 potentially relevant nursing research papers and reviews were published between 1973 and 2014. Two reviewers independently reviewed the articles, leaving 85 primary research studies and 10 review papers in the nursing field to be included in the scoping review. Thirty-one relevant primary research papers and reviews were also identified in the non-nursing related industries literature.

Results: Research into 12h nursing shifts fell within five broad themes: 'risks to patients', 'patient experience', 'risks to staff', 'staff experience' and 'impact on the organisation of work'. There was inconclusive evidence of the effects of 12h shift patterns in all five themes, with some studies demonstrating positive impacts and others negative or no impacts. This also mirrors the evidence in other, non-nursing related industries. The quality of research reviewed is generally weak and most studies focus on the risks, experience and work/life balance for staff, with few addressing the impact on patient outcomes and experience of care or work productivity.

Conclusions: There is insufficient evidence to justify the widespread implementation or withdrawal of 12h shifts in nursing. It is not clearly understood where there are real benefits and where there are real and unacceptable risks to patients and staff. More research focusing on the impact of 12h nursing shifts on patient safety and experience of care and on the long term impact on staff and work organisation is required.
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http://dx.doi.org/10.1016/j.ijnurstu.2014.10.014DOI Listing
February 2015

Comparison of serum, ear notches, and nasal and saliva swabs for Bovine viral diarrhea virus antigen detection in colostrum-fed persistently infected (PI) calves and non-PI calves.

J Vet Diagn Invest 2014 Nov 16;26(6):783-7. Epub 2014 Sep 16.

School of Animal and Veterinary Sciences, Roseworthy Campus, University of Adelaide, Roseworthy, South Australia, Australia.

The diagnosis of neonatal and young calves persistently infected (PI) with Bovine viral diarrhea virus (BVDV) by antigen-capture enzyme-linked immunosorbent assay (ACE) may be complicated by interference from colostrum-derived specific antibodies. Ten calves, with 3 calves identified as PI and 7 as non-PI were used in the current study. All non-PI calves were shown to be seropositive for BVDV-specific antibodies by antibody enzyme-linked immunosorbent assay (Ab-ELISA) on serum. Serum samples, ear notch samples, and nasal and saliva swabs were collected from each calf from birth until 12 weeks of age and tested by ELISA for BVDV-specific antigen and antibodies. Following colostrum ingestion, Ab-ELISA sample-to-positive (S/P) ratios rose by a mean of 0.95 (95% confidence interval [CI] = 0.64-1.25) and 1.72 (95% CI = 1.55-1.89) in seropositive, non-PI calves and in PI calves, respectively. The mean S/P ratios then declined to approximately 1.1 in non-PI calves and 0.5 in PI calves at between 60 and 80 days of age. In PI calves, testing for antigen in serum and nasal and saliva swabs was subject to interference by colostrum-derived antibodies in calves up to 3 weeks of age. Nasal swabs were less affected than serum and saliva swabs. Ear notches maintained positive ACE corrected optical densities at all sample times, despite a drop in the signal following the ingestion of colostrum.
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http://dx.doi.org/10.1177/1040638714550181DOI Listing
November 2014

Interprofessional teamwork in stroke care: Is it visible or important to patients and carers?

J Interprof Care 2015 26;29(4):331-9. Epub 2014 Aug 26.

Cardiff School of Social Sciences, Cardiff University , Cardiff , UK and.

Interprofessional teamwork is seen in healthcare policy and practice as a key strategy for providing safe, efficient and holistic healthcare and is an accepted part of evidence-based stroke care. The impact of interprofessional teamwork on patient and carer experience(s) of care is unknown, although some research suggests a relationship might exist. This study aimed to explore patient and carer perceptions of good and poor teamwork and its impact on experiences of care. Critical incident interviews were conducted with 50 patients and 33 carers in acute, inpatient rehabilitation and community phases of care within two UK stroke care pathways. An analytical framework, derived from a realist synthesis of 13 'mechanisms' (processes) of interprofessional teamwork, was used to identify positive and negative 'indicators' of teamwork. Participants identified several mechanisms of teamwork, but it was not a subject most talked about readily. This suggests that interprofessional teamwork is not a concept that is particularly important to stroke patients and carers; they do not readily perceive any impacts of teamwork on their experiences. These findings are a salient reminder that what might be expected by healthcare professionals to be important influences on experience may not be perceived to be so by patients and carers.
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http://dx.doi.org/10.3109/13561820.2014.950727DOI Listing
December 2016

Using realist synthesis to understand the mechanisms of interprofessional teamwork in health and social care.

J Interprof Care 2014 Nov 22;28(6):501-6. Epub 2014 Jul 22.

Cardiff School of Social Sciences, Cardiff University , Cardiff , UK and.

Realist synthesis offers a novel and innovative way to interrogate the large literature on interprofessional teamwork in health and social care teams. This article introduces realist synthesis and its approach to identifying and testing the underpinning processes (or "mechanisms") that make an intervention work, the contexts that trigger those mechanisms and their subsequent outcomes. A realist synthesis of the evidence on interprofessional teamwork is described. Thirteen mechanisms were identified in the synthesis and findings for one mechanism, called "Support and value" are presented in this paper. The evidence for the other twelve mechanisms ("collaboration and coordination", "pooling of resources", "individual learning", "role blurring", "efficient, open and equitable communication", "tactical communication", "shared responsibility and influence", "team behavioural norms", "shared responsibility and influence", "critically reviewing performance and decisions", "generating and implementing new ideas" and "leadership") are reported in a further three papers in this series. The "support and value" mechanism referred to the ways in which team members supported one another, respected other's skills and abilities and valued each other's contributions. "Support and value" was present in some, but far from all, teams and a number of contexts that explained this variation were identified. The article concludes with a discussion of the challenges and benefits of undertaking this realist synthesis.
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http://dx.doi.org/10.3109/13561820.2014.939744DOI Listing
November 2014

Evidence of collaboration, pooling of resources, learning and role blurring in interprofessional healthcare teams: a realist synthesis.

J Interprof Care 2015 Jan 22;29(1):20-5. Epub 2014 Jul 22.

Faculty of Health, Social Care and Education, Kingston University and St George's, University of London, Kingston Hill Campus, Kingston Upon Thames , Surrey , UK and.

Interprofessional teamwork has become an integral feature of healthcare delivery in a wide range of conditions and services in many countries. Many assumptions are made in healthcare literature and policy about how interprofessional teams function and about the outcomes of interprofessional teamwork. Realist synthesis is an approach to reviewing research evidence on complex interventions which seeks to explore these assumptions. It does this by unpacking the mechanisms of an intervention, exploring the contexts which trigger or deactivate them and connecting these contexts and mechanisms to their subsequent outcomes. This is the second in a series of four papers reporting a realist synthesis of interprofessional teamworking. The paper discusses four of the 13 mechanisms identified in the synthesis: collaboration and coordination; pooling of resources; individual learning; and role blurring. These mechanisms together capture the day-to-day functioning of teams and the dependence of that on members' understanding each others' skills and knowledge and learning from them. This synthesis found empirical evidence to support all four mechanisms, which tentatively suggests that collaboration, pooling, learning, and role blurring are all underlying processes of interprofessional teamwork. However, the supporting evidence for individual learning was relatively weak, therefore there may be assumptions made about learning within healthcare literature and policy that are not founded upon strong empirical evidence. There is a need for more robust research on individual learning to further understand its relationship with interprofessional teamworking in healthcare.
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http://dx.doi.org/10.3109/13561820.2014.939745DOI Listing
January 2015

Evidence of communication, influence and behavioural norms in interprofessional teams: a realist synthesis.

J Interprof Care 2015 Mar 22;29(2):100-5. Epub 2014 Jul 22.

Cardiff School of Social Sciences, Cardiff University , Cardiff , UK and.

This article is the third in a series reporting the process and findings of a realist synthesis of interprofessional teamwork in health and social care. The synthesis articulated and tested four "mechanisms" (processes) of teamwork related to communication and found variable evidence to support them. Evidence was strongest for "efficient, open and equitable communication" and "tactical communication", but lacking for the shared responsibility element of the "shared responsibility and influence" mechanism. Little evidence was found to support or oppose the mechanism, "team behavioural norms", so its status as a mechanism of interprofessional teamwork is unclear. A striking finding for all the mechanisms was the dearth of information on how they affected patient clinical outcomes and experiences.
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http://dx.doi.org/10.3109/13561820.2014.941458DOI Listing
March 2015

Evidence of a shared purpose, critical reflection, innovation and leadership in interprofessional healthcare teams: a realist synthesis.

J Interprof Care 2015 May 22;29(3):209-15. Epub 2014 Jul 22.

Faculty of Health, Social Care and Education, Kingston University and St George's University of London , Surrey, London , UK and.

Realist synthesis is a theory-driven approach for evaluating complex interventions using empirical evidence, which seeks an explanatory analysis of who a complex intervention works for, how, why, and in what circumstances. Interprofessional teamworking in healthcare is one such complex intervention, as teams are influenced by social and organizational factors, which makes them highly variable and context dependent. This article concludes a series of four articles that report on a realist synthesis of interprofessional teamworking. The synthesis identified 13 mechanisms that are reported in the literature to be the underlying processes through which interprofessional teamworking produces its effects. This article explores four of these mechanisms: a shared purpose; critical reflection; innovation; and leadership. These mechanisms together explain how a team sets and maintains its focus and direction. This article highlights that whilst many assumptions are made within the healthcare literature about how these mechanisms operate within teams, these assumptions are not always founded upon strong empirical evidence.
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http://dx.doi.org/10.3109/13561820.2014.941459DOI Listing
May 2015

The zebrafish reference genome sequence and its relationship to the human genome.

Nature 2013 Apr 17;496(7446):498-503. Epub 2013 Apr 17.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
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http://dx.doi.org/10.1038/nature12111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927PMC
April 2013

Sequencing and comparative analysis of the gorilla MHC genomic sequence.

Database (Oxford) 2013 15;2013:bat011. Epub 2013 Apr 15.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1HH, UK.

Major histocompatibility complex (MHC) genes play a critical role in vertebrate immune response and because the MHC is linked to a significant number of auto-immune and other diseases it is of great medical interest. Here we describe the clone-based sequencing and subsequent annotation of the MHC region of the gorilla genome. Because the MHC is subject to extensive variation, both structural and sequence-wise, it is not readily amenable to study in whole genome shotgun sequence such as the recently published gorilla genome. The variation of the MHC also makes it of evolutionary interest and therefore we analyse the sequence in the context of human and chimpanzee. In our comparisons with human and re-annotated chimpanzee MHC sequence we find that gorilla has a trimodular RCCX cluster, versus the reference human bimodular cluster, and additional copies of Class I (pseudo)genes between Gogo-K and Gogo-A (the orthologues of HLA-K and -A). We also find that Gogo-H (and Patr-H) is coding versus the HLA-H pseudogene and, conversely, there is a Gogo-DQB2 pseudogene versus the HLA-DQB2 coding gene. Our analysis, which is freely available through the VEGA genome browser, provides the research community with a comprehensive dataset for comparative and evolutionary research of the MHC.
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http://dx.doi.org/10.1093/database/bat011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626023PMC
June 2013

How to develop a patient and carer advisory group in stroke care research.

Nurse Res 2013 Jan;20(3):6-11

Faculty of Health and Social Care Sciences, Kingston University, UK.

Aim: The aim of this paper is to inform and advise researchers on the practical issues associated with involving stroke patients and their carers in research.

Background: The involvement of patients and carers in research is increasingly recognised as important, yet researchers are often unclear on how to do this in practice. This is particularly evident in the field of stroke care, where there is limited information available about how to involve stroke patients and their carers in research effectively, or about the difficulties associated with this.

Data Source: Experience of developing a patient and carer advisory group.

Review Methods: This paper reflects on the process the authors undertook when developing a stroke patient and darer advisory group as part of a research study exploring the effect of interprofessional team working on the experiences and outcomes after stroke of patients and carers.

Discussion: This paper discusses the challenges and the benefits of deveong a stroke patient and carer and advisory group, and offers advice to other researchers undertaking a similar process. It aims to provide some practical suggestions that may aid researchers wishing to involve stroke patients and carers in their research.

Conclusion: Stroke patients are likely to be older and have long-term physical disabilities or communication problems that may make their involvement in research more challenging to implement. However, with planning and consideration and the allocation of sufficient time and resources, stroke patients and their carers can be effectively involved, resulting in benefits to the research process and output, and to researchers, patients and carers.

Implications For Practice/research: Pay attention to planning and the practical details of involving stroke patients and their carers in research, ensuring that meetings are arranged in an accessible venue. Use straightforward language in all forms of communication. Listen carefully to their views and perspectives and be prepared to make changes to the study and revise methods if appropriate.
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http://dx.doi.org/10.7748/nr2013.01.20.3.6.c9490DOI Listing
January 2013

The Medicago genome provides insight into the evolution of rhizobial symbioses.

Nature 2011 Nov 16;480(7378):520-4. Epub 2011 Nov 16.

Department of Plant Pathology, University of Minnesota, St Paul, Minnesota 55108, USA.

Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing ∼94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox.
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http://dx.doi.org/10.1038/nature10625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272368PMC
November 2011

Genomic libraries: II. Subcloning, sequencing, and assembling large-insert genomic DNA clones.

Methods Mol Biol 2011 ;772:59-81

Sequencing Research and Development, Wellcome Trust Sanger Institute, Cambridge, UK.

Sequencing large insert clones to completion is useful for characterizing specific genomic regions, identifying haplotypes, and closing gaps in whole genome sequencing projects. Despite being a standard technique in molecular laboratories, DNA sequencing using the Sanger method can be highly problematic when complex secondary structures or sequence repeats are encountered in genomic clones. Here, we describe methods to isolate DNA from a large insert clone (fosmid or BAC), subclone the sample, and sequence the region to the highest industry standard. Troubleshooting solutions for sequencing difficult templates are discussed.
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http://dx.doi.org/10.1007/978-1-61779-228-1_4DOI Listing
February 2012

Genomic libraries: I. Construction and screening of fosmid genomic libraries.

Methods Mol Biol 2011 ;772:37-58

Sequencing Research and Development, Wellcome Trust Sanger Institute, Cambridge, UK.

Large insert genome libraries have been a core resource required to sequence genomes, analyze haplotypes, and aid gene discovery. While next generation sequencing technologies are revolutionizing the field of genomics, traditional genome libraries will still be required for accurate genome assembly. Their utility is also being extended to functional studies for understanding DNA regulatory elements. Here, we present a detailed method for constructing genomic fosmid libraries, testing for common contaminants, gridding the library to nylon membranes, then hybridizing the library membranes with a radiolabeled probe to identify corresponding genomic clones. While this chapter focuses on fosmid libraries, many of these steps can also be applied to bacterial artificial chromosome libraries.
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http://dx.doi.org/10.1007/978-1-61779-228-1_3DOI Listing
February 2012

Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry.

Nature 2011 Aug 14;477(7363):203-6. Epub 2011 Aug 14.

CNRS UMR 7205, Muséum National d'Histoire Naturelle, CP50, 45 Rue Buffon, 75005 Paris, France.

Supergenes are tight clusters of loci that facilitate the co-segregation of adaptive variation, providing integrated control of complex adaptive phenotypes. Polymorphic supergenes, in which specific combinations of traits are maintained within a single population, were first described for 'pin' and 'thrum' floral types in Primula and Fagopyrum, but classic examples are also found in insect mimicry and snail morphology. Understanding the evolutionary mechanisms that generate these co-adapted gene sets, as well as the mode of limiting the production of unfit recombinant forms, remains a substantial challenge. Here we show that individual wing-pattern morphs in the polymorphic mimetic butterfly Heliconius numata are associated with different genomic rearrangements at the supergene locus P. These rearrangements tighten the genetic linkage between at least two colour-pattern loci that are known to recombine in closely related species, with complete suppression of recombination being observed in experimental crosses across a 400-kilobase interval containing at least 18 genes. In natural populations, notable patterns of linkage disequilibrium (LD) are observed across the entire P region. The resulting divergent haplotype clades and inversion breakpoints are found in complete association with wing-pattern morphs. Our results indicate that allelic combinations at known wing-patterning loci have become locked together in a polymorphic rearrangement at the P locus, forming a supergene that acts as a simple switch between complex adaptive phenotypes found in sympatry. These findings highlight how genomic rearrangements can have a central role in the coexistence of adaptive phenotypes involving several genes acting in concert, by locally limiting recombination and gene flow.
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http://dx.doi.org/10.1038/nature10341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717454PMC
August 2011

Population genomics of domestic and wild yeasts.

Nature 2009 Mar 11;458(7236):337-41. Epub 2009 Feb 11.

Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.

Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of studies looking at ecological and geographic distributions, population structure and sexual versus asexual reproduction. Less well understood at the whole genome level are the evolutionary processes acting within populations and species that lead to adaptation to different environments, phenotypic differences and reproductive isolation. Here we present one- to fourfold or more coverage of the genome sequences of over seventy isolates of the baker's yeast S. cerevisiae and its closest relative, Saccharomyces paradoxus. We examine variation in gene content, single nucleotide polymorphisms, nucleotide insertions and deletions, copy numbers and transposable elements. We find that phenotypic variation broadly correlates with global genome-wide phylogenetic relationships. S. paradoxus populations are well delineated along geographic boundaries, whereas the variation among worldwide S. cerevisiae isolates shows less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.
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http://dx.doi.org/10.1038/nature07743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659681PMC
March 2009
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