排序方式： 共有46条查询结果，搜索用时 0 毫秒
1.
The epidemiology of leprosy is characterized by heterogeneity in susceptibility and clustering of disease within households. We aim to assess the extent to which different mechanisms for heterogeneity in leprosy susceptibility can explain household clustering as observed in a large study among contacts of leprosy patients.We used a microsimulation model, parameterizing it with data from over 20,000 contacts of leprosy patients in Bangladesh. We simulated six mechanisms producing heterogeneity in susceptibility: (1) susceptibility was allocated at random to persons (i.e. no additional mechanism), (2) a household factor, (3, 4) a genetic factor (dominant or recessive), or (5, 6) half a household factor and half genetic. We further assumed that a fraction of 5%, 10%, and 20% of the population was susceptible, leading to a total of 18 scenarios to be fitted to the data. We obtained an acceptable fit for each of the six mechanisms, thereby excluding none of the possible underlying mechanisms for heterogeneity of susceptibility to leprosy. However, the distribution of leprosy among contacts did differ between mechanisms, and predicted trends in the declining leprosy case detection were dependent on the assumed mechanism, with genetic-based susceptibility showing the slowest decline. Clustering of leprosy within households is partially caused by an increased transmission within households independent of the leprosy susceptibility mechanism. Even a large and detailed data set on contacts of leprosy patients could not unequivocally reveal the mechanism most likely responsible for heterogeneity in leprosy susceptibility. 相似文献
2.
3.
The first step of many metabolomics studies is quenching, a technique vital for rapidly halting metabolism and ensuring that the metabolite profile remains unchanging during sample processing. The most widely used approach is to plunge the sample into prechilled cold methanol; however, this led to significant metabolite loss in Synecheococcus sp. PCC 7002. Here we describe our analysis of the impacts of cold methanol quenching on the model marine cyanobacterium Synechococcus sp. PCC 7002, as well as our brief investigation of alternative quenching methods. We tested several methods including cold methanol, cold saline, and two filtration approaches. Targeted central metabolites were extracted and metabolomic profiles were generated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results indicate that cold methanol quenching induces dramatic metabolite leakage in Synechococcus, resulting in a majority of central metabolites being lost prior to extraction. Alternatively, usage of a chilled saline quenching solution mitigates metabolite leakage and improves sample recovery without sacrificing rapid quenching of cellular metabolism. Finally, we illustrate that metabolite leakage can be assessed, and subsequently accounted for, in order to determine absolute metabolite pool sizes; however, our results show that metabolite leakage is inconsistent across various metabolite pools and therefore must be determined for each individually measured metabolite. 相似文献
4.
The cardiac output of isolated working rat heart and left ventricular pressure were estimated in either almost complete inhibition of creatine kinase by iodoacetamide or predominant fall in adenine nucleotides (AdN) content induced by 2-deoxyglucose treatment. In the former case, a profound cardiac pump failure was observed despite almost normal levels of myocardial AdN and phosphocreatine. Those hearts could not maintain the aortic output at standard load due to lower LV systolic pressure, that was accompanied by increased minimal and maximal diastolic pressures by 5-7 mm Hg as well as by LV diastolic stiffness. As LV systolic pressure in those hearts was unchanged in retrogradely perfused and unloaded hearts it might be suggested that the cardiac pump failure was caused by the decreased LV distensibility. On the contrary, deoxyglucose treatment that resulted in 70% fall in the AdN content was accompanied by only moderate reduction of the cardiac output and insignificant changes in LV diastolic pressure and stiffness. The results suggested that creatine kinase plays a crucial role in the maintenance of normal myofibrillar compliance, which is necessary for cardiac filling and pump function. 相似文献
5.
Luc E. Coffeng Wilma A. Stolk Achim Hoerauf Dik Habbema Roel Bakker Adrian D. Hopkins Sake J. de Vlas 《PloS one》2014,9(12)
The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently. 相似文献
6.
Federica Gugole Luc E. Coffeng Wouter Edeling Benjamin Sanderse Sake J. de Vlas Daan Crommelin 《PLoS computational biology》2021,17(9)
Many countries are currently dealing with the COVID-19 epidemic and are searching for an exit strategy such that life in society can return to normal. To support this search, computational models are used to predict the spread of the virus and to assess the efficacy of policy measures before actual implementation. The model output has to be interpreted carefully though, as computational models are subject to uncertainties. These can stem from, e.g., limited knowledge about input parameters values or from the intrinsic stochastic nature of some computational models. They lead to uncertainties in the model predictions, raising the question what distribution of values the model produces for key indicators of the severity of the epidemic. Here we show how to tackle this question using techniques for uncertainty quantification and sensitivity analysis. We assess the uncertainties and sensitivities of four exit strategies implemented in an agent-based transmission model with geographical stratification. The exit strategies are termed Flattening the Curve, Contact Tracing, Intermittent Lockdown and Phased Opening. We consider two key indicators of the ability of exit strategies to avoid catastrophic health care overload: the maximum number of prevalent cases in intensive care (IC), and the total number of IC patient-days in excess of IC bed capacity. Our results show that uncertainties not directly related to the exit strategies are secondary, although they should still be considered in comprehensive analysis intended to inform policy makers. The sensitivity analysis discloses the crucial role of the intervention uptake by the population and of the capability to trace infected individuals. Finally, we explore the existence of a safe operating space. For Intermittent Lockdown we find only a small region in the model parameter space where the key indicators of the model stay within safe bounds, whereas this region is larger for the other exit strategies. 相似文献
7.
Ryan E. Wiegand Fiona M. Fleming Anne Straily Susan P. Montgomery Sake J. de Vlas Jürg Utzinger Penelope Vounatsou W. Evan Secor 《PLoS neglected tropical diseases》2021,15(6)
BackgroundRecent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a “background” level of morbidity.MethodologyData obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%.Principal findingsAn infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels.Conclusions/significanceA target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria. 相似文献
8.
Wilma A. Stolk Quirine A. ten Bosch Sake J. de Vlas Peter U. Fischer Gary J. Weil Ann S. Goldman 《PLoS neglected tropical diseases》2013,7(1)
The Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020. 相似文献
9.
Savitha S. Desai Swati Hegde Preeti Inamdar Nagaraj Sake M. S. Aravind 《Engineering in Life Science》2010,10(4):361-367
Isolation of two keratinolytic bacterial strains from poultry soil as well as purification and properties of keratinase were investigated. Isolates were designated as KI8101 and KI8102 (KI, keratin isolates) and were identified as Bacillus subtilis and B. licheniformis respectively. The purified enzyme from KI8102 exhibited a high specific activity of 500 U/mg with 71‐fold purification and 41% yield. SDS‐PAGE analysis indicated that the purified keratinase had a molecular mass of 32 kDa. The optimum temperature and pH were 50°C and 7.5, respectively. Its Km was 83.3 μM and Vmax was 71.4 μmol/mL min. The bacterium could potentially degrade keratin waste such as human hair, nails, bovine hair and wool. Therefore, the enzyme could improve the nutritional value of meat and poultry‐processing waste containing keratin and could be a potential candidate for biotechnological processing involving keratin hydrolysis. 相似文献
10.
Luc E. Coffeng Wilma A. Stolk Honorat G. M. Zouré J. Lennert Veerman Koffi B. Agblewonu Michele E. Murdoch Mounkaila Noma Grace Fobi Jan Hendrik Richardus Donald A. P. Bundy Dik Habbema Sake J. de Vlas Uche V. Amazigo 《PLoS neglected tropical diseases》2013,7(1)