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Wellcome Open Research

Patricia Doumbe-Belisse, Carmene Sandra Ngadjeu, Nadege Sonhafouo-Chiana, Abdou Talipouo, Landre Djamouko-Djonkam, Edmond Kopya, Roland Bamou, Jean Claude Toto, Souleyman Mounchili, Raymond Tabue, Parfait Awono-Ambene, Charles Sinclair Wondji, Flobert Njiokou, Christophe Antonio-Nkondjio
Background: Malaria remains a major public health problem in Cameroon; however, despite reports on the adaptation of anopheline species to urban habitats, there is still not enough information on malaria transmission pattern in urban settings. In the frame of a larval control trial in the city of Yaoundé, we conducted baseline surveys to assess malaria transmission dynamics in this city. Methods: Adult mosquitoes were collected indoors and outdoors using CDC light traps and human landing catches from March 2017 to March 2018 in 30 districts of Yaoundé, Cameroon...
2018: Wellcome Open Research
Hector M Diaz-Albiter, Clément Regnault, Edubiel A Alpizar-Sosa, Dagmara McGuinness, Michael Barrett, Rod J Dillon
Background: The leishmaniases are neglected diseases that affect some of the most vulnerable populations in the tropical and sub-tropical world. The parasites are transmitted by sand flies and novel strategies to control this neglected vector-borne disease are needed. Blocking transmission by targeting the parasite inside the phlebotomine vector offers potential in this regard. Some experimental approaches can be best performed by longitudinal study of parasites within flies, for which non-destructive methods to identify infected flies and to follow parasite population changes are required...
2018: Wellcome Open Research
May Ee Png, Melina Dritsaki, Alastair Gray, Rafael Pinedo-Villanueva, Oliver Rivero-Arias, Jagdeep Nanchahal
Dupuytren's disease (DD) is a common fibroproliferative condition of the palmar and digital fascia of the hand; however, there is currently no approved treatment for early stage DD. The objective of this paper is to describe the methods applied to assess the cost-effectiveness of adalimumab injections compared to placebo for controlling the progression of early stage DD in the Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD) trial. Measure of effectiveness and resource use will be obtained from a randomised clinical trial, carried out in three healthcare centres, and recruiting a minimum of 138 patients aged 18 years and above with a diagnosis of early stage DD...
2018: Wellcome Open Research
Mathupanee Oonsivilai, Yin Mo, Nantasit Luangasanatip, Yoel Lubell, Thyl Miliya, Pisey Tan, Lorn Loeuk, Paul Turner, Ben S Cooper
Background : Early and appropriate empiric antibiotic treatment of patients suspected of having sepsis is associated with reduced mortality. The increasing prevalence of antimicrobial resistance reduces the efficacy of empiric therapy guidelines derived from population data. This problem is particularly severe for children in developing country settings. We hypothesized that by applying machine learning approaches to readily collect patient data, it would be possible to obtain individualized predictions for targeted empiric antibiotic choices...
2018: Wellcome Open Research
Mathilde M V Pascal, Andreas C Themistocleous, Ralf Baron, Andreas Binder, Didier Bouhassira, Geert Crombez, Nanna B Finnerup, Janne Gierthmühlen, Yelena Granovsky, Leif Groop, Harry L Hebert, Troels S Jensen, Kristinn Johnsen, Mark I McCarthy, Weihua Meng, Colin N A Palmer, Andrew S C Rice, Jordi Serra, Romà Solà, David Yarnitsky, Blair H Smith, Nadine Attal, David L H Bennett
Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in large cohorts. The DOLORisk study aims to study these factors. Protocol: Multicentre cross-sectional and longitudinal cohorts covering the main causes leading to neuropathic pain (e...
2018: Wellcome Open Research
Toni-Kim Clarke, Yanni Zeng, Lauren Navrady, Charley Xia, Chris Haley, Archie Campbell, Pau Navarro, Carmen Amador, Mark J Adams, David M Howard, Aleix Soler, Caroline Hayward, Pippa A Thomson, Blair H Smith, Sandosh Padmanabhan, Lynne J Hocking, Lynsey S Hall, David J Porteous, Ian J Deary, Andrew M McIntosh
Background: Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable and genetic risk for SLEs is correlated with risk for MDD. We sought to investigate the genetic and environmental contributions to SLEs in a family-based sample, and quantify genetic overlap with MDD and neuroticism. Methods: A subset of Generation Scotland: the Scottish Family Health Study (GS), consisting of 9618 individuals with information on MDD, past 6 month SLEs, neuroticism and genome-wide genotype data was used in the present study...
2018: Wellcome Open Research
Thomas Battram, Luke Hoskins, David A Hughes, Johannes Kettunen, Susan M Ring, George Davey Smith, Nicholas J Timpson
Background: Genome-wide association studies have identified genetic variants associated with coronary artery disease (CAD) in adults - the leading cause of death worldwide. It often occurs later in life, but variants may impact CAD-relevant phenotypes early and throughout the life-course. Cohorts with longitudinal and genetic data on thousands of individuals are letting us explore the antecedents of this adult disease. Methods: 149 metabolites, with a focus on the lipidome, measured using nuclear magnetic resonance ( 1 H-NMR) spectroscopy, and genotype data were available from 5,905 individuals at ages 7, 15, and 17 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort...
2018: Wellcome Open Research
Harold Akehurst, M Amalia Pesantes, S Del Pilar Cornejo, Katty Manrique, Maria Lazo-Porras, Jill Portocarrero, Francisco Diez-Canseco, Antonio Bernabe-Ortiz, Antonio J Trujillo, J Jaime Miranda
Background: Weight loss is important for the control of type 2 diabetes mellitus but is difficult to achieve and sustain. Programmes employing financial incentives have been successful in areas such as smoking cessation. However, the optimum design for an incentivised programme for weight loss is undetermined, and may depend on social, cultural and demographic factors. Methods: An original questionnaire was designed whose items addressed respondent personal and health characteristics, and preferences for a hypothetical incentivised weight loss programme...
2018: Wellcome Open Research
Maxwell Robert Morgan, Owen Gwilym Roberts, Aled Morgan Edwards
M4K Pharma was incorporated to launch an open science drug discovery program that relies on regulatory exclusivity as its primary intellectual property and commercial asset, in lieu of patents.In many cases and in key markets, using regulatory exclusivity can provide equivalent commercial protection to patents, while also being compatible with open science. The model is proving attractive to government, foundation and individual funders, who collectively have different expectations for returns on investment compared with biotech, pharmaceutical companies, or venture capital investors...
2018: Wellcome Open Research
April Hartley, Diana L Santos Ferreira, Emma L Anderson, Debbie A Lawlor
Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis...
2018: Wellcome Open Research
Megan Vaughan, Albert Dube, Hazel Namadingo, Amelia Crampin, Levie Gondwe, Green Kapira, Joyce Mbughi, Maisha Nyasulu
Interviews were conducted with a small group of Malawians over the age of 60 in rural Karonga district and in Area 25 of the capital, Lilongwe. We asked their views on the changes in diet that had taken place over their lifetimes and also on the causes of 'noncommunicable' diseases, such as Type 2 diabetes and hypertension in their communities. Their answers generally confirmed research showing that dietary diversity is decreasing in Malawi, but many of our interviewees also recalled that hunger was more frequently experienced in the past...
2018: Wellcome Open Research
Margaret Nampijja, Robert Kizindo, Barbara Apule, Swaib Lule, Lawrence Muhangi, Andrew Titman, Alison Elliott, Katie Alcock, Charlie Lewis
Background: The home environment is reported to contribute significantly to children's developing cognitive skills. However, it is not yet evident whether this role prevails in the context of extreme poverty and frequent ill-health. We therefore investigated the role of the home environment in Ugandan children taking into account the frequent infections and extreme poverty in which they lived. Methods: Cognitive abilities of 163 5-year-old children were assessed. Home environments of these children, their health status and family socioeconomic status (SES) were assessed respectively using the EC-HOME, anthropometry and illnesses, and traditional SES measures...
2018: Wellcome Open Research
Charlene M C Rodrigues, Hannah Chan, Caroline Vipond, Keith Jolley, Odile B Harrison, Jun Wheeler, Gail Whiting, Ian M Feavers, Martin C J Maiden
Background: Protein-conjugate capsular polysaccharide vaccines can potentially control invasive meningococcal disease (IMD) caused by five (A, C, W, X, Y) of the six IMD-associated serogroups.  Concerns raised by immunological similarity of the serogroup B capsule, to human neural cell carbohydrates, has meant that 'serogroup B substitute' vaccines target more variable subcapsular protein antigens.  A successful approach using outer membrane vesicles (OMVs) as major vaccine components had limited strain coverage...
2018: Wellcome Open Research
Anne Wajja, Milly Namutebi, Barbara Apule, Gloria Oduru, Samuel Kiwanuka, Mirriam Akello, Beatrice Nassanga, Joyce Kabagenyi, Juma Mpiima, Samantha Vermaak, Alison Lawrie, Iman Satti, Jaco Verweij, Stephen Cose, Jonathan Levin, Pontiano Kaleebu, Edridah Tukahebwa, Helen McShane, Alison M Elliott
Background: A more effective vaccine for tuberculosis (TB) is a global public health priority. Vaccines under development will always need evaluation in endemic settings, most of which have limited resources. Adolescents are an important target population for a new TB vaccine and for other vaccines which are relevant at school-age. However, in most endemic settings there is limited experience of trials of investigational products among adolescents, and adolescents are not routinely vaccinated. Methods: We used Modified vaccinia Ankara-expressing Ag85A (MVA85A), a well-tolerated candidate vaccine for tuberculosis, to assess the effect of Schistosoma mansoni infection on vaccine immunogenicity among Ugandan adolescents in primary school...
2018: Wellcome Open Research
Anna Smielewska, Callum Pearson, Ashley Popay, Iain Roddick, Mark Reacher, Edward Emmott, Jenny He, Rachel Thaxter, Carol Chenery, Ian Goodfellow, Amos Burke, Hamid Jalal
Background: Human parainfluenza viruses (HPIVs) are significant causes of both upper and lower respiratory tract infections with type 3 (HPIV3) causing the most severe disease in the immunocompromised cohorts.  The objective of this study was to analyse the epidemiological nature of a cluster of cases of HPIV3 in a pediatric oncology unit of a major teaching hospital. Methods: In order to determine whether the activity observed represented a deviation from the norm, seasonal trends of HPIV3 in the surrounding geographical area as well as on the ward in question were analysed...
2018: Wellcome Open Research
Decha Tangseefa, Krishna Monthathip, Naruemol Tuenpakdee, Andrea König, Ladda Kajeechiwa, May Myo Thwin, Suphak Nosten, Saw Win Tun, Kayin Ma, Ahmar Hashmi, Khin Maung Lwin, Phaik Yeong Cheah, Lorenz von Seidlein, Francois Nosten
Background: In light of growing antimalarial drug resistance in Southeast Asia, control programmes have become increasingly focused on malaria elimination, composed of mass drug administration coupled with prompt diagnosis and treatment of symptomatic cases. The key to a successful elimination programme centres on high participation rates in targeted communities, often enhanced by community engagement (CE) efforts. Social science research was conducted to develop a conceptual framework used for CE activities in the Targeted Malaria Elimination programme, as a cross-border operation in Karen/Kayin State, Myanmar...
2018: Wellcome Open Research
Jayne Ellis, Prosperity C Eneh, Kenneth Ssebambulidde, Morris K Rutakingirwa, Mohammed Lamorde, Joshua Rhein, Fiona V Cresswell, David R Boulware, Melanie R Nicol
In 2016, 10.4 million cases of tuberculosis (TB) were reported globally. Malaria also continues to be a global public health threat. Due to marked epidemiological overlap in the global burden of TB and malaria, co-infection does occur. An HIV-infected, 32-year-old male presented with a two-week history of headache with fevers to Mulago National Referral Hospital, Uganda. Five months prior, he was diagnosed with pulmonary TB. He endorsed poor adherence to anti-tuberculous medications. Mycobacterium tuberculosis in CSF was confirmed on Xpert MTB/RIF Ultra...
2018: Wellcome Open Research
Stephen B Gordon, Lameck Chinula, Ben Chilima, Victor Mwapasa, Sufia Dadabhai, Yohannie Mlombe
Background: Research participant remuneration has been variable and inconsistent world-wide for many years owing to uncertainty regarding best practice and a lack of written guidelines for investigators and research ethics committees.  Recent recommendations are that researchers and regulators should develop regionally appropriate written guidelines to define reasonable remuneration based on expense reimbursement, compensation for time and burden associated with participation.   Incentives to motivate participation are acceptable in specific circumstances...
2018: Wellcome Open Research
J Jaime Miranda, María Lazo-Porras, Antonio Bernabe-Ortiz, M Amalia Pesantes, Francisco Diez-Canseco, Socorro Del Pilar Cornejo, Antonio J Trujillo
Background: Incentives play a role in introducing health-related benefits, but no interventions using mixed incentives, i.e. a combination of individual and group incentives, have been tested in individuals with type 2 diabetes mellitus (T2DM). We evaluated the feasibility of implementing individual- and mixed-incentives, with and without a supportive partner, on glycated haemoglobin (HbA1c) control and weight loss among patients with T2DM. Methods: This is a feasibility, sex-stratified, single-blinded, randomized controlled study in individuals with T2DM...
2018: Wellcome Open Research
Sreedevi Padmanabhan, Malay Ranjan Biswal, Ravi Manjithaya, Meher K Prakash
Unconventional protein secretion (UPS) is an important phenomenon with fundamental implications to cargo export. How eukaryotic proteins transported by UPS are recognized without a conventional signal peptide has been an open question. It was recently observed that a diacidic amino acid motif (ASP-GLU or DE) is necessary for the secretion of superoxide dismutase 1 (SOD1) from yeast under nutrient starvation. Taking cue from this discovery, we explore the hypothesis of whether the diacidic motif DE, which can occur fairly ubiquitously, along with its context, can be a generic signal for unconventional secretion of proteins...
2018: Wellcome Open Research
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