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Wellcome Open Research

John A Lees, Michelle Kendall, Julian Parkhill, Caroline Colijn, Stephen D Bentley, Simon R Harris
Background : Phylogenetic reconstruction is a necessary first step in many analyses which use whole genome sequence data from bacterial populations. There are many available methods to infer phylogenies, and these have various advantages and disadvantages, but few unbiased comparisons of the range of approaches have been made. Methods : We simulated data from a defined "true tree" using a realistic evolutionary model. We built phylogenies from this data using a range of methods, and compared reconstructed trees to the true tree using two measures, noting the computational time needed for different phylogenetic reconstructions...
2018: Wellcome Open Research
Hiroaki Mano, Gopal Kotecha, Kenji Leibnitz, Takashi Matsubara, Aya Nakae, Nicholas Shenker, Masahiko Shibata, Valerie Voon, Wako Yoshida, Michael Lee, Toshio Yanagida, Mitsuo Kawato, Maria Joao Rosa, Ben Seymour
Background. Chronic pain is a common, often disabling condition thought to involve a combination of peripheral and central neurobiological factors. However, the extent and nature of changes in the brain is poorly understood. Methods. We investigated brain network architecture using resting-state fMRI data in chronic back pain patients in the UK and Japan (41 patients, 56 controls), as well as open data from USA. We applied machine learning and deep learning (conditional variational autoencoder architecture) methods to explore classification of patients/controls based on network connectivity...
2018: Wellcome Open Research
Dianne F Newbury, Nuala H Simpson, Paul A Thompson, Dorothy V M Bishop
Background : The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. Group averages, however, obscure a wide range of outcomes. Hypothesis: The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. Neuroligin-4 genes are expressed from X and Y chromosomes; they play an important role in synaptic development and have been implicated in neurodevelopment...
2018: Wellcome Open Research
Ana B A Wallis, Conrad A Nieduszynski
Background: Understanding DNA replication initiation is essential to understand the mis-regulation of replication seen in cancer and other human disorders. DNA replication initiates from DNA replication origins. In eukaryotes, replication is dependent on cell cycle kinases which function during S phase. Dbf4-dependent kinase (DDK) and cyclin-dependent kinase (CDK) act to phosphorylate the DNA helicase (composed of mini chromosome maintenance proteins: Mcm2-7) and firing factors to activate replication origins...
2018: Wellcome Open Research
Rogier A Kievit, Delia Fuhrmann, Gesa Sophia Borgeest, Ivan L Simpson-Kent, Richard N A Henson
Background:  Fluid intelligence declines with advancing age, starting in early adulthood. Within-subject declines in fluid intelligence are highly correlated with contemporaneous declines in the ability to live and function independently. To support healthy aging, the mechanisms underlying these declines need to be better understood. Methods:  In this pre-registered analysis, we applied latent growth curve modelling to investigate the neural determinants of longitudinal changes in fluid intelligence across three time points in 185,317 individuals (N=9,719 two waves, N=870 three waves) from the UK Biobank (age range: 39-73 years)...
2018: Wellcome Open Research
Innocent Djègbè, Romaric Akoton, Genevieve Tchigossou, Koffi Mensah Ahadji-Dabla, Seun Michael Atoyebi, Razack Adéoti, Francis Zeukeng, Guillaume Koffivi Ketoh, Rousseau Djouaka
Background: To optimize the success of insecticide-based malaria control intervention, knowledge of the distribution of Anopheles gambiae species and insecticide resistance mechanisms is necessary. This paper reported an updated data on pyrethroids/DDT resistance in the An. gambiae s.l population from Togo.  Methods: From December 2013 to April 2015, females of indoor-resting An. gambiae s.l were captured in three locations belonging to three different ecological zones. Resistance to DDT, permethrin and deltamethrin was screened in F1 progeny of collected mosquitoes using WHO susceptibility tests...
2018: Wellcome Open Research
Adeolu B Adewoye, Nick Shrine, Linda Odenthal-Hesse, Samantha Welsh, Anders Malarstig, Scott Jelinsky, Iain Kilty, Martin D Tobin, Edward J Hollox, Louise V Wain
Background: The CCL3L1-CCR5 signaling axis is important in a number of inflammatory responses, including macrophage function, and T-cell-dependent immune responses. Small molecule CCR5 antagonists exist, including the approved antiretroviral drug maraviroc, and therapeutic monoclonal antibodies are in development. Repositioning of drugs and targets into new disease areas can accelerate the availability of new therapies and substantially reduce costs. As it has been shown that drug targets with genetic evidence supporting their involvement in the disease are more likely to be successful in clinical development, using genetic association studies to identify new target repurposing opportunities could be fruitful...
2018: Wellcome Open Research
Rachel J Skilton, Yibing Wang, Colette O'Neill, Simone Filardo, Peter Marsh, Angèle Bénard, Nicholas R Thomson, Kyle H Ramsey, Ian N Clarke
Background: Research in chlamydial genetics is challenging because of its obligate intracellular developmental cycle. In vivo systems exist that allow studies of different aspects of basic biology of chlamydiae, the murine Chlamydia muridarum model is one of great importance and thus an essential research tool. C. muridarum carries a plasmid that has a role in virulence.  Our aim was to compare and contrast the C. muridarum plasmid-free phenotype with that of a chromosomally isogenic plasmid-bearing strain, through the inclusion phase of the developmental cycle...
2018: Wellcome Open Research
Diane L Sherman, Peter J Brophy
Charcot-Marie-Tooth (CMT) disease comprises up to 80 monogenic inherited neuropathies of the peripheral nervous system (PNS) that collectively result in demyelination and axon degeneration. The majority of CMT disease is primarily either dysmyelinating or demyelinating in which mutations affect the ability of Schwann cells to either assemble or stabilize peripheral nerve myelin. CMT4F is a recessive demyelinating form of the disease caused by mutations in the Periaxin ( PRX ) gene . Periaxin (Prx) interacts with Dystrophin Related Protein 2 (Drp2) in an adhesion complex with the laminin receptor Dystroglycan (Dag)...
2018: Wellcome Open Research
Victoria Cavero, Francisco Diez-Canseco, Mauricio Toyama, Gustavo Flórez Salcedo, Alessandra Ipince, Ricardo Araya, J Jaime Miranda
Background: This study aimed to understand the offer of mental health care at the primary care level, collecting the views of psychologists, primary health care providers (PHCPs), and patients, with a focus on health services in which patients attend regularly and who present a higher prevalence of mental disorders. Methods: A qualitative study was conducted in antenatal care, tuberculosis, HIV/AIDS, and chronic diseases services from six primary health care centers. Semi-structured interviews were conducted with psychologists, PHCPs, and patients working in or attending the selected facilities...
2018: Wellcome Open Research
Robert Butcher, Oliver Sokana, Kelvin Jack, Leslie Sui, Charles Russell, Anna Last, Diana L Martin, Matthew J Burton, Anthony W Solomon, David C W Mabey, Chrissy H Roberts
Background: The low population-prevalence of trachomatous trichiasis and high prevalence of trachomatous inflammation-follicular (TF) provide contradictory estimates of the magnitude of the public health threat from trachoma in the Solomon Islands. Improved characterisation of the biology of trachoma in the region may support policy makers as they decide what interventions are required. Here, age-specific profiles of anti-Pgp3 antibodies and conjunctival scarring were examined to determine whether there is evidence of ongoing transmission and pathology from ocular Chlamydia trachomatis (Ct) infection...
2018: Wellcome Open Research
Kate Gooding, Regina Makwinja, Deborah Nyirenda, Robin Vincent, Rodrick Sambakunsi
Background: Evaluation of community and public engagement in research is important to deepen understanding of how engagement works and to enhance its effectiveness. Theories of change have been recommended for evaluating community engagement, for their ability to make explicit intended outcomes and understandings of how engagement activities contribute to these outcomes. However, there are few documented examples of using theories of change for evaluation of engagement. This article reports experience of using theories of change to develop a framework for evaluating community engagement in research at a clinical research organisation in Malawi...
2018: Wellcome Open Research
Felix Stein, Devi Sridhar
Global health is increasingly reliant on financial markets. The ongoing financialisation of global health raises new questions of governance, which we expect to affect policy makers as much as doctors, nurses and patients in the years to come. In this editorial, we will first explain what is meant by financialisation, then illustrate its nature in the field of global health via three examples, and end by highlighting some of the governance issues that the financialisation of global health raises.
2018: Wellcome Open Research
Laurence Thielemans, Gornpan Gornsawun, Borimas Hanboonkunupakarn, Moo Kho Paw, Pen Porn, Paw Khu Moo, Bart Van Overmeire, Stephane Proux, François Nosten, Rose McGready, Verena I Carrara, Germana Bancone
Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age...
2018: Wellcome Open Research
Dennis Waithaka, Benjamin Tsofa, Edwine Barasa
Background : Decentralization of health systems has made sub-national/regional healthcare systems the backbone of healthcare delivery. These regions are tasked with the difficult responsibility of determining healthcare priorities and resource allocation amidst scarce resources. We aimed to review empirical literature that evaluated priority setting practice at the meso level of health systems. Methods : We systematically searched PubMed, ScienceDirect and Google scholar databases and supplemented these with manual searching for relevant studies, based on the reference list of selected papers...
2018: Wellcome Open Research
Thomas Brendan Smith, Kamlesh Patel, Haydn Munford, Andrew Peet, Daniel A Tennant, Mark Jeeves, Christian Ludwig
Tracing the fate of stable isotopically-enriched nutrients is a sophisticated method of describing and quantifying the activity of metabolic pathways. Nuclear Magnetic Resonance (NMR) offers high resolution data, yet is under-utilised due to length of time required to collect the data, quantification requiring multiple samples and complicated analysis. Here we present two techniques, quantitative spectral filters and enhancement of the splitting due to J-coupling in 1 H, 13 C-HSQC NMR spectra, which allow the rapid collection of NMR data in a quantitative manner on a single sample...
2018: Wellcome Open Research
Gabriel Mouahid, Anne Rognon, Ronaldo de Carvalho Augusto, Patrick Driguez, Kathy Geyer, Shannon Karinshak, Nelia Luviano, Victoria Mann, Thomas Quack, Kate Rawlinson, George Wendt, Christoph Grunau, Hélène Moné
Schistosomiasis is an important parasitic disease, touching roughly 200 million people worldwide. The causative agents are different Schistosoma species. Schistosomes have a complex life cycle, with a freshwater snail as intermediate host. After infection, sporocysts develop inside the snail host and give rise to human dwelling larvae. We present here a detailed step-by-step video instruction in English, French, Spanish and Portuguese that shows how these sporocysts can be manipulated and transferred from one snail to another...
2018: Wellcome Open Research
Gavin Miller
This article uses the mass-media career of the British psychiatrist David Stafford-Clark (1916-1999) as a case study in the exercise of cultural authority by celebrity medical professionals in post-war Britain. Stafford-Clark rose to prominence in the mass media, particularly through his presenting work on medical and related topics for BBC TV and Radio, and was in the vanguard of psychiatrists and physicians who eroded professional edicts on anonymity. At the height of his career, he traded upon his celebrity status, and consequent cultural authority, to deliver mass media sermons on a variety of social, cultural, and political topics...
April 26, 2017: Wellcome Open Research
Kevin M Malone, Seamus G McGuinness, Eimear Cleary, Janis Jefferies, Christabel Owens, Cecily C Kelleher
Background: Suicide is a significant public health concern, which impacts on health outcomes. Few suicide research studies have been interdisciplinary. We combined a psychobiographical autopsy with a visual arts autopsy, in which families donated stories, images and objects associated with the lived life of a loved one lost to suicide. From this interdisciplinary research platform, a mediated exhibition was created (Lived Lives) with artist, scientist and families, co-curated by communities, facilitating dialogue, response and public action around suicide prevention...
April 13, 2017: Wellcome Open Research
Mandy Peffers, Andrew R Jones, Antony McCabe, James Anderson
Experiments involving mass spectrometry (MS)-based proteomics are widely used for analyses of connective tissues. Common examples include the use of relative quantification to identify differentially expressed peptides and proteins in cartilage and tendon. We are working on characterising so-called 'neopeptides', i.e. peptides formed due to native cleavage of proteins, for example under pathological conditions. Unlike peptides typically quantified in MS workflows due to the in vitro use of an enzyme such as trypsin, a neopeptide has at least one terminus that was not due to the use of trypsin in the workflow...
April 7, 2017: Wellcome Open Research
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