Prevalence study of yaws in the Democratic Republic of Congo using the lot quality assurance sampling method.

BACKGROUND: Until the 1970s the prevalence of non-venereal trepanomatosis, including yaws, was greatly reduced after worldwide mass treatment. In 2005, cases were again reported in the Democratic Republic of the Congo. We carried out a survey to estimate the village-level prevalence of yaws in the region of Equator in the north of the country in order to define appropriate strategies to effectively treat the affected population. METHODOLOGY/PRINCIPAL FINDINGS: We designed a community-based survey using the Lot Quality Assurance Sampling method to classify the prevalence of active yaws in 14 groups of villages (lots). The classification into high, moderate, or low yaws prevalence corresponded to World Health Organization prevalence thresholds for identifying appropriate operational treatment strategies. Active yaws cases were defined by suggestive clinical signs and positive rapid plasma reagin and Treponema pallidum hemagglutination serological tests. The overall prevalence in the study area was 4.7% (95% confidence interval: 3.4-6.0). Two of 14 lots had high prevalence (>10%), three moderate prevalence (5-10%) and nine low prevalence (<5%.). CONCLUSIONS/SIGNIFICANCE: Although yaws is no longer a World Health Organization priority disease, the presence of yaws in a region where it was supposed to be eradicated demonstrates the importance of continued surveillance and control efforts. Yaws should remain a public health priority in countries where previously it was known to be endemic. The integration of sensitive surveillance systems together with free access to effective treatment is recommended. As a consequence of our study results, more than 16,000 people received free treatment against yaws

Amélioration de la qualité des sols acides de Lubumbashi (Katanga, RD Congo) par l’application de différents niveaux de compost de fumiers de poules

Objectives: An experiment was conducted on an acidic soil to assess the influence of compost and mineral fertilizers on the chemical properties of this soil. Methodology and results: The test was installed to a completely randomized with six replicates of six treatment: T0 (unfertilized control), T1 (175 kg NPK+ 87 kg urea per hectare) T2 (double of T1, 350 kg NPK+175 kg urea) T3 (15t.ha-1 of compost), T4 (double of T3, 30 t.ha-1 of compost) T5 (quadruple of T3, 60 t.ha-1 of compost). Before installation of the test, composting chicken manure was carried out for 36 days. At the end of the experiment, chemical analyzes were performed on samples of soil and compost from manure of hens. The contents of exchangeable cations appear to be higher compared to the reference values found by other authors in the study area. The high values found for these parameters in the site of the present study could result from the contribution of fertilizers. For the witness, there was a low nutrient availability. In addition, the mean levels of K, P, C and pH are high in pots amended with plenty of compost. Significant differences were observed between the different doses of compost and mineral NPK fertilizer on soil characteristics studied. Conclusion and application: Recovery of waste as a source of organic matter is a practice to be encouraged in Lubumbashi urban horticulture, in given the high cost of mineral fertilizers and the low level of income of farmers.Keywords: Compost; mineral fertilizers; acid soil; urban and peri-urban agriculture; Lubumbashi

Oral fexinidazole for stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: a prospective, multicentre, open-label, cohort study

BACKGROUND: Staging and treatment of human African trypanosomiasis caused by Trypanosoma brucei gambiense (g-HAT) required lumbar puncture to assess cerebrospinal fluid (CSF) and intravenous drugs that cross the blood-brain barrier for late-stage infection. These procedures are inconvenient in rural health systems of disease-endemic countries. A pivotal study established fexinidazole as the first oral monotherapy to be effective against non-severe stage 2 g-HAT. We aimed to assess the safety and efficacy of fexinidazole in early g-HAT. METHODS: In this prospective, multicentre, open-label, single-arm cohort study, patients with stage 1 or early stage 2 g-HAT were recruited from eight treatment centres in the Democratic Republic of the Congo. Primary inclusion criteria included being older than 15 years, being able to ingest at least one complete meal per day (or at least one sachet of Plumpy'Nut®), a Karnofsky score higher than 50, evidence of trypanosomes in the blood or lymph but no evidence of trypanosomes in the CSF, willingness to be admitted to hospital to receive treatment, having a permanent address, and being able to comply with the follow-up visit schedule. Exclusion criteria included severe malnutrition, inability to take medication orally, pregnant or breastfeeding women, any clinically important medical condition that could jeopardise patient safety or participation in the study, severely deteriorated general status, any contraindication to imidazole drugs, HAT treatment in the past 2 years, previous enrolment in the study or previous intake of fexinidazole, abnormalities on electrocardiogram that did not return to normal in pretreatment repeated assessments or were considered clinically important, QT interval corrected using Fridericia's formula of at least 450 ms, and patients not tested for malaria or not having received appropriate treatment for malaria or for soil-transmitted helminthiasis. Patients were classified into stage 1 or early stage 2 g-HAT groups following evidence of trypanosomes in the blood, lymph, and absence in CSF, and using white-blood-cell count in CSF. Patients received 1800 mg fexinidazole once per day on days 1-4 then 1200 mg fexinidazole on days 5-10. Patients were observed for approximately 19 months in total. Study participants were followed up on day 5 and day 8 during treatment, at end of treatment on day 11, at end of hospitalisation on days 11-18, at week 9 for a subset of patients, and after 6 months, 12 months, and 18 months. The primary endpoint was treatment success at 12 months. Safety was assessed through routine monitoring. Analyses were done in the intention-to-treat population. The acceptable success rate was defined as treatment efficacy in more than 80% of patients. This study is completed and registered with ClinicalTrials.gov (NCT02169557). FINDINGS: Patients were enrolled between April 30, 2014, and April 25, 2017. 238 patients were recruited: 195 (82%) patients with stage 1 g-HAT and 43 (18%) with early stage 2 g-HAT. 189 (97%) of 195 patients with stage 1 g-HAT and 41 (95%) of 43 patients with early stage 2 g-HAT were finally included and completed the 10 day treatment period. Three patients with stage 1 g-HAT died after the 10 day treatment period and before the 12 month primary follow-up visit, considered as treatment failure and were withdrawn from the study. Treatment was effective at 12 months for 227 (99%) of 230 patients (95% CI 96·2-99·7): 186 (98%) of 189 patients (95·4-99·7) with stage 1 and 41 (100%) of 41 patients (91·4-100·0) with early stage 2, indicating that the primary study endpoint was met. No new safety issues were observed. The most frequent adverse events were headache and vomiting. In total, 214 (93%) of 230 patients had treatment-emergent adverse events, mainly common-terminology criteria for adverse events grades 1 to 3. None led to treatment discontinuation. INTERPRETATION: Fexinidazole is a valuable first-line treatment option in the early stages of g-HAT. FUNDING: Through the Drugs for Neglected Diseases initiative: the Bill & Melinda Gates Foundation, the Republic and Canton of Geneva (Switzerland), the Dutch Ministry of Foreign Affairs (also known as DGIS; Netherlands), the Norwegian Agency for Development Cooperation (also known as Norad; Norway), the Federal Ministry of Education and Research (also known as BMBF) through KfW (Germany), the Brian Mercer Charitable Trust (UK), and other private foundations and individuals from the HAT campaign

Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial

Summary Background Human African trypanosomiasis caused by Trypanosoma brucei gambiense (gambiense HAT) in patients with late-stage disease requires hospital admission to receive nifurtimox-eflornithine combination therapy (NECT). Fexinidazole, the latest treatment that has been recommended by WHO, also requires systematic admission to hospital, which is problematic in areas with few health-care resources. We aim to assess the safety and efficacy of acoziborole in adult and adolescent patients with gambiense HAT. Methods This multicentre, prospective, open-label, single-arm, phase 2/3 study recruited patients aged 15 years or older with confirmed gambiense HAT infection from ten hospitals in the Democratic Republic of the Congo and Guinea. Inclusion criteria included a Karnofsky score less than 50, ability to swallow tablets, a permanent address or traceability, ability to comply with follow-up visits and study requirements, and agreement to hospital admission during treatment. Oral acoziborole was administered as a single 960 mg dose (3 × 320 mg tablets) to fasted patients. Patients were observed in hospital until day 15 after treatment administration then for 18 months as outpatients with visits at 3, 6, 12, and 18 months. The primary efficacy endpoint was the success rate of acoziborole treatment at 18 months in patients with late-stage gambiense HAT (modified intention-to-treat [mITT] population), based on modified WHO criteria. A complementary post-hoc analysis comparing the 18-month success rates for acoziborole and NECT (using historical data) was performed. This study is registered at ClinicalTrials.gov, NCT03087955. Findings Between Oct 11, 2016, and March 25, 2019, 260 patients were screened, of whom 52 were ineligible and 208 were enrolled (167 with late-stage and 41 with early-stage or intermediate-stage gambiense HAT; primary efficacy analysis set). All 41 (100%) patients with early-stage or intermediate-stage and 160 (96%) of 167 with late-stage disease completed the last 18-month follow-up visit. The mean age of participants was 34·0 years (SD 12·4), including 117 (56%) men and 91 (44%) women. Treatment success rate at 18 months was 95·2% (95% CI 91·2-97·7) reached in 159 of 167 patients with late-stage gambiense HAT (mITT population) and 98·1% (95·1-99·5) reached in 159 of 162 patients (evaluable population). Overall, 155 (75%) of 208 patients had 600 treatment-emergent adverse events. A total of 38 drug-related treatment-emergent adverse events occurred in 29 (14%) patients; all were mild or moderate and most common were pyrexia and asthenia. Four deaths occurred during the study; none were considered treatment related. The post-hoc analysis showed similar results to the estimated historical success rate for NECT of 94%. Interpretation Given the high efficacy and favourable safety profile, acoziborole holds promise in the efforts to reach the WHO goal of interrupting HAT transmission by 2030. Funding Bill & Melinda Gates Foundation, UK Aid, Federal Ministry of Education and Research, Swiss Agency for Development and Cooperation, Médecins Sans Frontières, Dutch Ministry of Foreign Affairs, Norwegian Agency for Development Cooperation, Norwegian Ministry of Foreign Affairs, the Stavros Niarchos Foundation, Spanish Agency for International Development Cooperation, and the Banco Bilbao Vizcaya Argentaria Foundation. Translation For the French translation of the abstract see Supplementary Materials section

Management and outcomes following emergency surgery for traumatic brain injury - A multi-centre, international, prospective cohort study (the Global Neurotrauma Outcomes Study).

Introduction:Traumatic brain injury (TBI) accounts for a significant amount of death and disability worldwide and the majority of this burden affects individuals in low-and-middle income countries. Despite this, considerable geographical differences have been reported in the care of TBI patients. On this background, we aim to provide a comprehensive international picture of the epidemiological characteristics, management and outcomes of patients undergoing emergency surgery for traumatic brain injury (TBI) worldwide. Methods and analysis:The Global Neurotrauma Outcomes Study (GNOS) is a multi-centre, international, prospective observational cohort study. Any unit performing emergency surgery for TBI worldwide will be eligible to participate. All TBI patients who receive emergency surgery in any given consecutive 30-day period beginning between 1st of November 2018 and 31st of December 2019 in a given participating unit will be included. Data will be collected via a secure online platform in anonymised form. The primary outcome measures for the study will be 14-day mortality (or survival to hospital discharge, whichever comes first). Final day of data collection for the primary outcome measure is February 13th. Secondary outcome measures include return to theatre and surgical site infection. Ethics and dissemination:This project will not affect clinical practice and has been classified as clinical audit following research ethics review. Access to source data will be made available to collaborators through national or international anonymised datasets on request and after review of the scientific validity of the proposed analysis by the central study team

Matricellular Proteins Produced by Melanocytes and Melanomas: In Search for Functions

Matricellular proteins are modulators of cell-matrix interactions and cellular functions. The group includes thrombospondin, osteopontin, osteonectin/SPARC, tenascin, disintegrins, galectins and CCN proteins. The production of matricellular proteins such as osteopontin, SPARC or tenascin is highly upregulated in melanoma and other tumors but little is known about their functions in tumor growth, survival, and metastasis. The distribution pattern of CCN3 differs from most other matricellular proteins, such that it is produced abundantly by normal melanocytes, but is not significantly expressed in melanoma cells. CCN3 is known to inhibit melanocyte proliferation and stimulate adhesion to collagen type IV, the main component of the basement membrane. CCN3 has a unique role in securing adhesion of melanocytes to the basement membrane distinct from other melanoma-produced matricellular proteins which act as de-adhesive molecules and antagonists of focal adhesion. Qualitative and quantitative changes in matricellular protein expression contribute to melanoma progression similar to the E-cadherin to N-cadherin class switch, allowing melanoma cells to escape from keratinocyte control

Prediction of the torsional capacity of CFDST steel columns using extreme gradient boosting tree-based machine learning technique

This study presents an eXtreme Gradient Boosting (XGBoost) algorithm for predicting the torsional capacity of circular Concrete-Filled Double Skin Tubular (CFDST) steel columns under pure torsion. Utilizing a dataset of 806 columns generated through non-linear finite element analysis, the of XGBoost model outperforms existing empirical models with R² values of 99.5% (training) and 97.6% (testing). SHapley Additive exPlanations (SHAP) framework aided in interpreting predictions at both global and local levels. Key influencing variables include concrete compressive strength, outer steel tube yield strength, outer steel tube thickness, and inner steel tube thickness. The study highlights the effectiveness XGBoost as a promising alternative to traditional empirical models for accurate torsional capacity predictions in CFDST steel columns

Reliability analysis of shear design provisions for cold formed steel sections

This study focuses on the structural reliability analysis of cold-formed steel (CFS) sections under the ultimate limit state of shear. It considers two design models: the EN 1993-1-3 standard and its recent modification proposed by a previous study. The bias and uncertainty in these models were calibrated by comparing the design models’ prediction to 67 experimental results. Reliability analyses for the CFS beams, designed according to both models, were conducted using Monte Carlo Simulation (MCS) and the First Order Reliability Method (FORM). This analysis incorporated the model uncertainty and other parameters describing these models into the stochastic description. The 10% fractile of the reliability values for beams designed using the existing EN 1993-1-3 provisions showed values that were more conservative than those of the modified EN 1993-1-3 provisions, compared to the reliability target of 3.8. A FORM sensitivity analysis identified the yield strength of steel fyb and the resistance model uncertainty ΓR as the main positive drivers of uncertainty in the computed reliability indices of the design models. Additionally, a multiplicative modification factor was proposed for both the existing and modified versions of EN 1993-1-3, ensuring that these models optimally meet the specified reliability targets of 3.8 and 4.3 for Eurocode reliability classes 2 and 3, respectively. The proposed modifications maintain the partial factor γM0 at 1.0, as stipulated by the EN 1993-1-3 provisions for the resistance of the cross-section.</p

Reliability analysis of shear design provisions for cold formed steel sections

This study focuses on the structural reliability analysis of cold-formed steel (CFS) sections under the ultimate limit state of shear. It considers two design models: the EN 1993-1-3 standard and its recent modification proposed by a previous study. The bias and uncertainty in these models were calibrated by comparing the design models’ prediction to 67 experimental results. Reliability analyses for the CFS beams, designed according to both models, were conducted using Monte Carlo Simulation (MCS) and the First Order Reliability Method (FORM). This analysis incorporated the model uncertainty and other parameters describing these models into the stochastic description. The 10% fractile of the reliability values for beams designed using the existing EN 1993-1-3 provisions showed values that were more conservative than those of the modified EN 1993-1-3 provisions, compared to the reliability target of 3.8. A FORM sensitivity analysis identified the yield strength of steel fyb and the resistance model uncertainty ΓR as the main positive drivers of uncertainty in the computed reliability indices of the design models. Additionally, a multiplicative modification factor was proposed for both the existing and modified versions of EN 1993-1-3, ensuring that these models optimally meet the specified reliability targets of 3.8 and 4.3 for Eurocode reliability classes 2 and 3, respectively. The proposed modifications maintain the partial factor γM0 at 1.0, as stipulated by the EN 1993-1-3 provisions for the resistance of the cross-section.</p