27 research outputs found
Food Crises and Asset Liquidation: Household-level Evidence from Tanzania
This paper studies the effects of food crisesâlarge and sudden increases in food pricesâon asset liquidation. Substantial research exists on household food insecurity as a result of a food crisis, but studies on householdsâ coping strategies have so far been limited to natural shocks such as flood, drought, and financial crises. In this paper, I use an adapted version of the asset-based poverty trap model to explain householdsâ use of asset liquidation as a coping strategy when faced with food crises. To test my theory, I employ a household-level panel data set from Tanzania that covers the years 2008, 2010, and 2012. I estimate fixed effects regressions of productive and unproductive asset levels on a measure of household-specific food prices. I find no statistically significant evidence in support of asset liquidation. My results suggest an asset smoothing behavior across all types of households
Prognostic factors for changes in the timed 4-stair climb in patients with Duchenne muscular dystrophy, and implications for measuring drug efficacy: A multi-institutional collaboration
The timed 4-stair climb (4SC) assessment has been used to measure function in Duchenne muscular dystrophy (DMD) practice and research. We sought to identify prognostic factors for changes in 4SC, assess their consistency across data sources, and the extent to which prognostic scores could be useful in DMD clinical trial design and analysis. Data from patients with DMD in the placebo arm of a phase 3 trial (Tadalafil DMD trial) and two real-world sources (Universitaire Ziekenhuizen, Leuven, Belgium [Leuven] and Cincinnati Children\u27s Hospital Medical Center [CCHMC]) were analyzed. One-year changes in 4SC completion time and velocity (stairs/second) were analyzed. Prognostic models included age, height, weight, steroid use, and multiple timed function tests and were developed using multivariable regression, separately in each data source. Simulations were used to quantify impacts on trial sample size requirements. Data on 1-year changes in 4SC were available from the Tadalafil DMD trial (n = 92) Leuven (n = 67), and CCHMC (n = 212). Models incorporating multiple timed function tests, height, and weight significantly improved prognostic accuracy for 1-year change in 4SC (R2: 29%-36% for 4SC velocity, and 29%-34% for 4SC time) compared to models including only age, baseline 4SC and steroid duration (R2:8%-17% for 4SC velocity and 2%-13% for 4SC time). Measures of walking and rising ability contributed important prognostic information for changes in 4SC. In a randomized trial with equal allocation to treatment and placebo, adjustment for such a prognostic score would enable detection (at 80% power) of a treatment effect of 0.25 stairs/second with 100-120 patients, compared to 170-190 patients without prognostic score adjustment. Combining measures of ambulatory function doubled prognostic accuracy for 1-year changes in 4SC completion time and velocity. Randomized clinical trials incorporating a validated prognostic score could reduce sample size requirements by approximately 40%. Knowledge of important prognostic factors can also inform adjusted comparisons to external controls
Land-surface characteristics and climate in West Africa : Modelsâ biases and impacts of historical anthropogenically-induced deforestation
Land Use Land-Cover Change (LULCC), such as deforestation, affects the climate system and land-atmosphere interactions. Using simulations carried out within the LUCID (Land Use and Climate, IDentification of robust Impacts) project framework, we first quantify the role of historical land-cover change induced by human activities on surface climate in West Africa. Focusing on two contrasted African regions, we find that climate responses of land-use changes are small but they are still statistically significant. In Western Sahel, a statistically significant near-surface atmospheric cooling and a decrease in water recycling are simulated in summer in response to LULCC. Over the Guinean zone, models simulate a significant decrease in precipitation and water recycling in autumn in response to LULCC. This signal is comparable in magnitude with the effect induced by the increase in greenhouse gases. Simulated climate changes due to historical LULCC could however be underestimated because: (i) the prescribed LULCC can be underestimated in those regions; (ii) the climate models underestimate the coupling strength between West African surface climate and leaf area index (LAI) and (iii) the lack of interactive LAI in some models. Finally, our study reveals indirect atmospheric processes triggered by LULCC. Over the Western Sahel, models reveal that a significant decrease in solar reflection tend to cool down the surface and thus counteract the atmospheric feedback. Conversely, over the Guinea zone, models reveal that the indirect atmospheric processes and turbulent heat fluxes dominate the climatic responses over the direct effects of LULCC
DMD Genotypes and Motor Function in Duchenne Muscular Dystrophy: A Multi-institution Meta-analysis With Implications for Clinical Trials
BACKGROUND AND OBJECTIVES: Clinical trials of genotype-targeted treatments in Duchenne muscular dystrophy (DMD) traditionally compare treated patients to untreated patients with the same DMD genotype class. This avoids confounding of drug efficacy by genotype effects but also shrinks the pool of eligible controls, increasing challenges for trial enrollment in this already rare disease. To evaluate the suitability of genotypically unmatched controls in DMD, we quantified effects of genotype class on 1-year changes in motor function endpoints used in clinical trials. METHODS: Over 1,600 patient-years of follow-up (>700 patients) were studied from six real-world/natural history data sources (UZ Leuven, PRO-DMD-01 shared by CureDuchenne, iMDEX, North Star UK, Cincinnati Children's Hospital Medical Center, and the DMD Italian Group), with genotypes classified as amenable to skipping exons 44, 45, 51 or 53, other skippable, nonsense, and other mutations. Associations between genotype class and 1-year changes in North Star Ambulatory Assessment total score (ÎNSAA) and in 10-meter walk/run velocity (Î10MWR) were studied in each data source with and without adjustment for baseline prognostic factors. RESULTS: The studied genotype classes accounted for approximately 2% of variation in ÎNSAA outcomes after 12 months, whereas other prognostic factors explained >30% of variation in large data sources. Based on a meta-analysis across all data sources, pooled effect estimates for the studied skip-amenable mutation classes were all small in magnitude (<2 units in ÎNSAA total score in 1-year follow up), smaller than clinically important differences in NSAA, and were precisely estimated with standard errors <1 unit after adjusting for non-genotypic prognostic factors. DISCUSSION: These findings suggest viability of trial designs incorporating genotypically mixed or unmatched controls for up to 12 months in duration for motor function outcomes, which would ease recruitment challenges and reduce numbers of patients assigned to placebos. Such trial designs, including multi-genotype platform trials and hybrid designs, should ensure baseline balance between treatment and control groups for the most important prognostic factors, while accounting for small remaining genotype effects quantified in the present study
High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations
Background: Emergence and spread of drug resistance to every anti-malarial used to date, creates an urgent need for development of sensitive, specifc and feld-deployable molecular tools for detection and surveillance of validated drug resistance markers. Such tools would allow early detection of mutations in resistance loci. The aim of this study was to compare common population signatures and drug resistance marker frequencies between two populations with diferent levels of malaria endemicity and history of anti-malarial drug use: Tanzania and SĂ©nĂ©gal. This was accomplished by implementing a high resolution melting assay to study molecular markers of drug resistance as compared to polymerase chain reactionârestriction fragment length polymorphism (PCR/RFLP) methodology.
Methods: Fifty blood samples were collected each from a lowly malaria endemic site (SĂ©nĂ©gal), and a highly malaria endemic site (Tanzania) from patients presenting with uncomplicated Plasmodium falciparum malaria at clinic. Data representing the DHFR were derived using both PCRâRFLP and HRM assay; while genotyping data representing the DHPS were evaluated in Senegal and Tanzania using HRM. Msp genotyping analysis was used to characterize the multiplicity of infection in both countries.
Results: A high prevalence of samples harbouring mutant DHFR alleles was observed in both population using both genotyping techniques. HRM was better able to detect mixed alleles compared to PCR/RFLP for DHFR codon 51 in Tanzania; and only HRM was able to detect mixed infections from Senegal. A high prevalence of mutant alleles in DHFR (codons 51, 59, 108) and DHPS (codon 437) were found among samples from Sénégal while no mutations were observed at DHPS codons 540 and 581, from both countries. Overall, the frequency of samples harbouring either a single DHFR mutation (S108N) or double mutation in DHFR (C59R/S108N) was greater in Sénégal compared to Tanzania
Conclusion: Here the results demonstrate that HRM is a rapid, sensitive, and feld-deployable alternative technique to PCRâRFLP genotyping that is useful in populations harbouring more than one parasite genome (polygenomic infections). In this study, a high levels of resistance polymorphisms was observed in both dhfr and dhps, among samples from Tanzania and SĂ©nĂ©gal. A routine monitoring by molecular markers can be a way to detect emergence of resistance involving a change in the treatment policy
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Ex vivo susceptibility and genotyping of Plasmodium falciparum isolates from Pikine, Senegal
Background: The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxineâpyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006. The purpose of this study is to assess the ex vivo sensitivity to different anti-malarial drugs of the P. falciparum population from Pikine. Methods: Fifty-four samples were collected from patients with non-complicated malaria and aged between 2 and 20 years in the Deggo health centre in Pikine in 2014. An assay in which parasites are stained with 4âČ, 6-di-amidino-2-phenylindole (DAPI), was used to study the ex vivo sensitivity of isolates to chloroquine, amodiaquine, piperaquine, pyrimethamine, and dihydroartemisinin. High resolution melting was used for genotyping of pfdhps, pfdhfr, pfmdr1, and pfcrt genes. Results: The mean IC50s of chloroquine, amodiaquine, piperaquine, dihydroartemisinin, and pyrimethamine were, respectively, 39.44, 54.02, 15.28, 2.23, and 64.70 nM. Resistance mutations in pfdhfr gene, in codon 437 of pfdhps gene, and an absence of mutation at position 540 of pfdhps were observed. Mutations in codons K76T of pfcrt and N86Y of pfmdr1 were observed at 51 and 11% population prevalence, respectively. A relationship was found between the K76T and N86Y mutations and ex vivo resistance to chloroquine. Conclusion: An increase in sensitivity of isolates to chloroquine was observed. A high sensitivity to dihydroartemisinin was observed; whereas, a decrease in sensitivity to pyrimethamine was observed in the parasite population from Pikine
EClinicalMedicine
BACKGROUND: As mortality remains high for patients with Ebola virus disease (EVD) despite new treatment options, the ability to level up the provided supportive care and to predict the risk of death is of major importance. This analysis of the EVISTA cohort aims to describe advanced supportive care provided to EVD patients in the Democratic Republic of the Congo (DRC) and to develop a simple risk score for predicting in-hospital death, called PREDS. METHODS: In this prospective cohort (NCT04815175), patients were recruited during the 10(th) EVD outbreak in the DRC across three Ebola Treatment Centers (ETCs). Demographic, clinical, biological, virological and treatment data were collected. We evaluated factors known to affect the risk of in-hospital death and applied univariate and multivariate Cox proportional-hazards analyses to derive the risk score in a training dataset. We validated the score in an internal-validation dataset, applying C-statistics as a measure of discrimination. FINDINGS: Between August 1(st) 2018 and December 31(th) 2019, 711 patients were enrolled in the study. Regarding supportive care, patients received vasopressive drug (n = 111), blood transfusion (n = 101), oxygen therapy (n = 250) and cardio-pulmonary ultrasound (n = 15). Overall, 323 (45%) patients died before day 28. Six independent prognostic factors were identified (ALT, creatinine, modified NEWS2 score, viral load, age and symptom duration). The final score range from 0 to 13 points, with a good concordance (C = 86.24%) and calibration with the Hosmer-Lemeshow test (p = 0.12). INTERPRETATION: The implementation of advanced supportive care is possible for EVD patients in emergency settings. PREDS is a simple, accurate tool that could help in orienting early advanced care for at-risk patients after external validation. FUNDING: This study was funded by ALIMA
Ex vivo susceptibility and genotyping of Plasmodium falciparum isolates from Pikine, Senegal
Les moisissures des grains de sorgho (Sorghum bicolor (L.) Moench.) : etiologie et pouvoir pathogene, desinfection fongicide des semences
SIGLECNRS TD Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc