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| 5. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 6. |
- Lienhardt, C, et al.
(författare)
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Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo
- 2002
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Ingår i: European Journal of Immunology. - 1521-4141. ; 32:6, s. 1605-1613
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Tidskriftsartikel (refereegranskat)abstract
- Activation of Th1 lymphocytes, IFN-gamma production and macrophage activation are crucial in defense against Mycobacteria. In developing countries, Th2 activation and IL-4 production have been associated in vitro with tuberculosis and with poor clinical outcome after treatment. Serological markers of Th1 [soluble lymphocyte activation gene (LAG)-3] and Th2 (IgE, soluble CD30, and CCL22/macrophage-derived chemokine) activity were measured in 414 HIV-negative tuberculosis patients from The Gambia and Guinee and in 414 healthy household and community controls. Measurements were repeated during treatment to assess the effect of therapy on Th1/Th2 ratio. At diagnosis, sLAG-3 levels were lower in patients than in community controls (p<0.0001), but were higher in household controls exposed to contact with patients than in community controls (p<0.0001). In comparison with community controls, patients had consistently higher levels of IgE, sCD30, and CCL22 (p<0.0001), whereas household controls had lower levels of indicators of Th2 activity (P<0.0001). After treatment, cured patients had higher levels of Th1 (p<0.0001) and lower levels of Th2 (p<0.0001) activity than patients who were not successfully treated or interrupted therapy. In Africa, tuberculosis is associated with low Th1 and high Th2 activity in vivo, whereas close exposure to tuberculosis is associated with a high Th1/Th2 ratio. Patients with favorable outcome after treatment exhibit a higher Th1/Th2 ratio compared to patients with poor clinical outcome.
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| 7. |
- Meyer, Michael F., et al.
(författare)
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Virtual Growing Pains : Initial Lessons Learned from Organizing Virtual Workshops, Summits, Conferences, and Networking Events during a Global Pandemic
- 2021
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Ingår i: Limnology and Oceanography Bulletin. - : John Wiley & Sons. - 1539-607X .- 1539-6088. ; 30:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- For many, 2020 was a year of abrupt professional and personal change. For the aquatic sciences community, many were adapting to virtual formats for conducting and sharing science, while simultaneously learning to live in a socially distanced world. Understandably, the aquatic sciences community postponed or canceled most in-person scientific meetings. Still, many scientific communities either transitioned annual meetings to a virtual format or inaugurated new virtual meetings. Fortunately, increased use of video conferencing platforms, networking and communication applications, and a general comfort with conducting science virtually helped bring the in-person meeting experience to scientists worldwide. Yet, the transition to conducting science virtually revealed new barriers to participation whereas others were lowered. The combined lessons learned from organizing a meeting constitute a necessary knowledge base that will prove useful, as virtual conferences are likely to continue in some form. To concentrate and synthesize these experiences, we showcase how six scientific societies and communities planned, organized, and conducted virtual meetings in 2020. With this consolidated information in hand, we look forward to a future, where scientific meetings embrace a virtual component, so to as help make science more inclusive and global.
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| 8. |
- Saint-Leger, A., et al.
(författare)
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The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres
- 2014
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Ingår i: Cell Cycle. - : Taylor andamp; Francis: STM, Behavioural Science and Public Health Titles. - 1538-4101 .- 1551-4005. ; 13:15, s. 2469-2479
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Tidskriftsartikel (refereegranskat)abstract
- The stability of mammalian telomeres depends upon TRF2, which prevents inappropriate repair and checkpoint activation. By using a plasmid integration assay in yeasts carrying humanized telomeres, we demonstrated that TRF2 possesses the intrinsic property to both stimulate initial homologous recombination events and to prevent their resolution via its basic N-terminal domain. In human cells, we further showed that this TRF2 domain prevents telomere shortening mediated by the resolvase-associated protein SLX4 as well as GEN1 and MUS81, 2 different types of endonucleases with resolvase activities. We propose that various types of resolvase activities are kept in check by the basic N-terminal domain of TRF2 in order to favor an accurate repair of the stalled forks that occur during telomere replication. © 2014 Landes Bioscience.
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- Sowe, Alieu, et al.
(författare)
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Epidemiology of measles cases, vaccine effectiveness, and performance towards measles elimination in The Gambia
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction In 2011, member states of the World Health Organization (WHO) Africa Regional Office (AFRO) resolved to eliminate Measles by 2020. Our study aims to assess The Gambia's progress towards the set AFRO measles elimination target and highlight surveillance and immunisation gaps to better inform future measles prevention strategies. Material and methods A retrospective review of measles surveillance data for the period 2011-2019, was extracted from The Gambia case-based measles surveillance database. WHO-UNICEF national coverage estimates were used for estimating national level MCV coverage. Measles post campaign coverage survey coverage estimates were used to estimate national measles campaign coverage. Results One hundred and twenty-five of the 863 reported suspected cases were laboratory confirmed as measles cases. More than half (53.6%) of the confirmed cases have unknown vaccination status, 24% of cases were vaccinated, 52.8% of cases occurred among males, and 72.8% cases were among urban residents. The incidence of measles cases per million population was lowest (0) in 2011-2012 and highest in 2015 and 2016 (31 and 23 respectively). The indicator for surveillance sensitivity was met in all years except in 2016 and 2019. Children aged 5-9 years (Incidence Rate Ratio-IRR = 0.6) and residents of Central River region (IRR = 0.21) had lower measles risk whilst unvaccinated (Adjusted IRR = 5.95) and those with unknown vaccination status (IRR 2.21) had higher measles risk. Vaccine effectiveness was 89.5%. Conclusion The Gambia's quest to attain measles elimination status by 2020 has registered significant success but it is unlikely that all target indicators will be met. Vaccination has been very effective in preventing cases. There is variation in measles risk by health region, and it will be important to take it into account when designing prevention and control strategies. The quality of case investigations should be improved to enhance the quality of surveillance for decision making.
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- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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- Flechard, Chris R., et al.
(författare)
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Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 1: Fluxes and budgets of carbon, nitrogen and greenhouse gases from ecosystem monitoring and modelling
- 2020
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 17:6, s. 1583-1620
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Tidskriftsartikel (refereegranskat)abstract
- The impact of atmospheric reactive nitrogen (N-r) deposition on carbon (C) sequestration in soils and biomass of unfertilized, natural, semi-natural and forest ecosystems has been much debated. Many previous results of this dC/dN response were based on changes in carbon stocks from periodical soil and ecosystem inventories, associated with estimates of N-r deposition obtained from large-scale chemical transport models. This study and a companion paper (Flechard et al., 2020) strive to reduce uncertainties of N effects on C sequestration by linking multi-annual gross and net ecosystem productivity estimates from 40 eddy covariance flux towers across Europe to local measurement-based estimates of dry and wet N-r deposition from a dedicated collocated monitoring network. To identify possible ecological drivers and processes affecting the interplay between C and N-r inputs and losses, these data were also combined with in situ flux measurements of NO, N2O and CH4 fluxes; soil NO3- leaching sampling; and results of soil incubation experiments for N and greenhouse gas (GHG) emissions, as well as surveys of available data from online databases and from the literature, together with forest ecosystem (BAS-FOR) modelling. Multi-year averages of net ecosystem productivity (NEP) in forests ranged from -70 to 826 gCm(-2) yr(-1) at total wet + dry inorganic N-r deposition rates (N-dep) of 0.3 to 4.3 gNm(-2) yr(-1) and from -4 to 361 g Cm-2 yr(-1) at N-dep rates of 0.1 to 3.1 gNm(-2) yr(-1) in short semi-natural vegetation (moorlands, wetlands and unfertilized extensively managed grasslands). The GHG budgets of the forests were strongly dominated by CO2 exchange, while CH4 and N2O exchange comprised a larger proportion of the GHG balance in short semi-natural vegetation. Uncertainties in elemental budgets were much larger for nitrogen than carbon, especially at sites with elevated N-dep where N-r leaching losses were also very large, and compounded by the lack of reliable data on organic nitrogen and N-2 losses by denitrification. Nitrogen losses in the form of NO, N2O and especially NO3- were on average 27%(range 6 %-54 %) of N-dep at sites with N-dep < 1 gNm(-2) yr(-1) versus 65% (range 35 %-85 %) for N-dep > 3 gNm(-2) yr(-1). Such large levels of N-r loss likely indicate that different stages of N saturation occurred at a number of sites. The joint analysis of the C and N budgets provided further hints that N saturation could be detected in altered patterns of forest growth. Net ecosystem productivity increased with N-r deposition up to 2-2.5 gNm(-2) yr(-1), with large scatter associated with a wide range in carbon sequestration efficiency (CSE, defined as the NEP/GPP ratio). At elevated N-dep levels (> 2.5 gNm(-2) yr(-1)), where inorganic N-r losses were also increasingly large, NEP levelled off and then decreased. The apparent increase in NEP at low to intermediate N-dep levels was partly the result of geographical cross-correlations between N-dep and climate, indicating that the actual mean dC/dN response at individual sites was significantly lower than would be suggested by a simple, straightforward regression of NEP vs. N-dep.
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- Kengne-Ouafo, Jonas A., et al.
(författare)
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The global transcriptome of Plasmodium falciparum midstage gametocytes (stages II–IV) appears largely conserved and gametocyte-specific gene expression patterns vary in clinical isolates
- 2023
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Our overall understanding of the developmental biology of malaria parasites has been greatly enhanced by recent advances in transcriptomic analysis. However, most of these investigations rely on laboratory strains (LS) that were adapted into in vitro culture many years ago, and the transcriptomes of clinical isolates (CI) circulating in human populations have not been assessed. In this study, RNA-seq was used to compare the global transcriptome of mid-stage gametocytes derived from three short-term cultured CI, with gametocytes derived from the NF54 reference laboratory strain. The core transcriptome appeared to be consistent between CI- and LS-derived gametocyte preparations, but some important differences were also observed. A majority of gametocyte-specific genes (43/53) appear to have relatively higher expression in CI-derived gametocytes than in LS-derived gametocytes, but a K-means clustering analysis showed that genes involved in flagellum- and microtubule-based processes (movement/motility) were more abundant in both groups, albeit with some differences between them. In addition, gametocytes from one CI described as CI group II gametocytes (CI:GGII) showed gene expression variation in the form of reduced gametocyte-specific gene expression compared to the other two CI-derived gametocytes (CI gametocyte group I, CI:GGI), although the mixed developmental stages used in our study is a potential confounder, only partially mitigated by the inclusion of multiple replicates for each CI. Overall, our study suggests that there may be subtle differences in the gene expression profiles of mid-stage gametocytes from CI relative to the NF54 reference strain of Plasmodium falciparum. Thus, it is necessary to deploy gametocyte-producing clinical parasite isolates to fully understand the diversity of gene expression strategies that may occur during the sequestered development of parasite sexual stages. IMPORTANCE Maturing gametocytes of Plasmodium falciparum are known to sequester away from peripheral circulation into the bone marrow until they are mature. Blocking gametocyte sequestration can prevent malaria transmission from humans to mosquitoes, but most studies aim to understand gametocyte development utilizing long-term adapted laboratory lines instead of clinical isolates. This is a particular issue for our understanding of the sexual stages, which are known to decrease rapidly during adaptation to long-term culture, meaning that many LS are unable to produce transmissible gametocytes. Using RNA-seq, we investigated the global transcriptome of mid-stage gametocytes derived from three clinical isolates and a reference strain (NF54). This identified important differences in gene expression profiles between immature gametocytes of CI and the NF54 reference strain of P. falciparum, suggesting increased investment in gametocytogenesis in clinical isolates. Our transcriptomic data highlight the use of clinical isolates in studying the morphological, cellular features and molecular biology of gametocytes.
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- Burgert-Brucker, Clara R., et al.
(författare)
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Risk factors associated with failing pre-transmission assessment surveys (pre-TAS) in lymphatic filariasis elimination programs : Results of a multi-country analysis
- 2020
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites-referred to as pre-transmission assessment surveys (pre-TAS)-in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value <= 0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS.
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- Gianni, Stefano, et al.
(författare)
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Mechanism of Na(+) binding to thrombin resolved by ultra-rapid kinetics
- 2007
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Ingår i: Biophysical Chemistry. - : Elsevier BV. - 0301-4622 .- 1873-4200. ; 131:1-3, s. 111-114
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of Na(+) and K(+) with proteins is at the basis of numerous processes of biological importance. However, measurement of the kinetic components of the interaction has eluded experimentalists for decades because the rate constants are too fast to resolve with conventional stopped-flow methods. Using a continuous-flow apparatus with a dead time of 50 micro s we have been able to resolve the kinetic rate constants and entire mechanism of Na(+) binding to thrombin, an interaction that is at the basis of the procoagulant and prothrombotic roles of the enzyme in the blood.
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- Jalloh, MF, et al.
(författare)
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Integrated digital system for community engagement and community-based surveillance during the 2014-2016 Ebola outbreak in Sierra Leone: lessons for future health emergencies
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Community engagement and community-based surveillance are essential components of responding to infectious disease outbreaks, but real-time data reporting remains a challenge. In the 2014–2016 Ebola outbreak in Sierra Leone, the Social Mobilisation Action Consortium was formed to scale-up structured, data-driven community engagement. The consortium became operational across all 14 districts and supported an expansive network of 2500 community mobilisers, 6000 faith leaders and 42 partner radio stations. The benefit of a more agile digital reporting system became apparent within few months of implementing paper-based reporting given the need to rapidly use the data to inform the fast-evolving epidemic. In this paper, we aim to document the design, deployment and implementation of a digital reporting system used in six high transmission districts. We highlight lessons learnt from our experience in scaling up the digital reporting system during an unprecedented public health crisis. The lessons learnt from our experience in Sierra Leone have important implications for designing and implementing similar digital reporting systems for community engagement and community-based surveillance during public health emergencies.
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| 20. |
- Wilson, S, et al.
(författare)
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Challenges and solutions to providing surgery in Sierra Leone hospitals: a qualitative analysis of surgical provider perspectives
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:2, s. e052972-
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to use qualitative interviews with surgical providers to explore challenges and solutions to providing surgical and anaesthesia care in Sierra Leone’s hospitals.DesignData were collected through anonymous, semistructured interviews. We used a qualitative framework approach to analyse interview data and determine themes relating to challenges that were reported.SettingA purposive sample of 12 hospitals was selected throughout Sierra Leone to include district and referral hospitals of varying ownership (private, non-governmental organisation and government).ParticipantsThe most senior surgical provider available during each hospital site visit participated in a semistructured interview. A total of 12 interviews were conducted.ResultsProviders described both challenges and solutions relating to the following categories: equipment and supplies, access to services, human resources, infrastructure, management and patient factors. These challenges were found to affect surgical care in hospitals by delaying surgical care, decreasing operative capacity and decreasing quality of care. Providers identified not only the root causes of these challenges, but also the varied workarounds and solutions they employ to overcome them.ConclusionSurgical providers can offer important insights into challenges affecting surgical services in hospitals. Despite working in challenging environments with limited resources, providers have developed innovative solutions to improve surgical and anaesthesia care in hospitals in Sierra Leone. Qualitative research has an important role to play in improving understanding of the challenges facing surgeons in low-income countries.
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