The effect of treatment delay on time-to-recovery in the presence of unobserved heterogeneity

We study the effect of delaying treatment in the presence of (unobserved) heterogeneity. In a homogeneous population and assuming a proportional treatment effect, a treatment delay period will result in notably lower cumulative recovery percentages. We show in theoretical scenarios using frailty models that if the population is heterogeneous, the effect of a delay period is much smaller. This can be explained by the selection process that is induced by the frailty. Patient groups that start treatment later have already undergone more selection. The marginal hazard ratio for the treatment will act differently in such a more homogeneous patient group. We further discuss modeling approaches for estimating the effect of treatment delay in the presence of heterogeneity, and compare their performance in a simulation study. The conventional Cox model that fails to account for heterogeneity overestimates the effect of treatment delay. Including interaction terms between treatment and starting time of treatment or between treatment and follow up time gave no improvement. Estimating a frailty term can improve the estimation, but is sensitive to misspecification of the frailty distribution. Therefore, multiple frailty distributions should be used and the results should be compared using the Akaike Information Criterion. Non-parametric estimation of the cumulative recovery percentages can be considered if the dataset contains sufficient long term follow up for each of the delay strategies. The methods are demonstrated on a motivating application evaluating the effect of delaying the start of treatment with assisted reproductive techniques on time-to-pregnancy in couples with unexplained subfertility.     

Spatial structure of stoloniferous herbs: an interplay between structural blue-print, ontogeny and phenotypic plasticity

Plant form and spatial structure reflect the basic architectural blue-print of a plant. In most plant species, the expression of the structural blue-print is systematically altered during ontogeny resulting in predictable changes in the allometry of plant structures and in the types of structures that are produced. The expression of the structural blue-print or the timing of ontogenetic changes is also frequently altered by environmental conditions. This latter source of variability, referred to as phenotypic plasticity, is manifested through changes in the timing and rates of meristem initiation and development, the likelihood that meristems will remain dormant or commit to different demographic fates (i.e., vegetative vs. reproductive structures), or the size and structure of the organs formed. Complex interactions among these components can result in considerable differences in form and spatial structure among individuals of the same species. This paper focuses on the importance of these different components in determining the architecture of clonal plants with long internode connections between ramets.A case study is presented that attempts to separate ontogenetic variation and phenotypic plasticity in two stoloniferous species with different structural blue-prints, in their responses to shading. In both species the rate of ontogenetic development responded to intermediate shading levels, but only at very low levels of light availability did plastic changes in branch formation occur. Under shaded conditions the two species achieved similar changes in their architecture in conspicuously different ways. We discuss how different mechanisms leading to a given architecture can be distinguished and what the ecological implications of this are.     

Miltefosine for the treatment of cutaneous leishmaniasis—A pilot study from Ethiopia

BackgroundCutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.Methodology and principal findingsIn an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.Conclusions/SignificanceBased on miltefosine’s good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04004754","term_id":"NCT04004754"}}NCT04004754.     

Influence of microorganism and plant oils on the structure of mannosylerythritol lipid (MEL) biosurfactants revealed by a novel thin layer chromatography mass spectrometry method

Journal of Industrial Microbiology & Biotechnology - Mannosylerythritol lipids (MEL) are microbial glycolipid biosurfactants with great potential for application in cosmetics and household...     

Nutritional and Health Status of Woolly Monkeys

Woolly monkeys (Lagothrix lagotricha and L. flavicauda) are threatened species in the wild and in captivity. Numerous zoological institutions have historically kept Lagothrix lagotricha spp., but only a few of them have succeeded in breeding populations. Therefore the majority of institutions that formerly kept Lagothrix lagotricha are no longer able or willing to do so. Captive populations of the species have frequent health problems, most significantly hypertension and related disorders. Researchers have conducted free-ranging dietary and behavior studies with respect to woolly monkeys, but have established no concrete link between diet or nutrients and captive health problems. The available literature we discuss indicates that researchers need to examine the link further. In addition, it is critical to the survival of the primates to be able to keep breeding populations in captivity owing to increasing natural pressures such as deforestation and hunting. Therefore, better understanding of the captive and free-ranging behavior and health parameters of the species is vital to ensure their survival and to maintain forest health and diversity. Researchers need to conduct large-scale research studies comparing the health and complete diet of individuals in the wild and captivity to resolve health problems facing the species in captivity.     

Parental Feeding Style and the Inter‐generational Transmission of Obesity Risk

Objective: This study was designed to determine whether a community sample of obese mothers with young children used different feeding styles compared with a matched sample of normal‐weight mothers. Four aspects of feeding style were assessed: emotional feeding, instrumental feeding (using food as a reward), prompting/encouragement to eat, and control over eating. Research Methods and Procedures: Participants were from 214 families with same‐sex twins; 100 families in which both parents were overweight or obese and 114 in which both parents were normal weight or lean. Results: We found that obese mothers were no more likely than normal‐weight mothers to offer food to deal with emotional distress, use food as a form of reward, or encourage the child to eat more than was wanted. The obese and normal‐weight mothers did differ on “control”; obese mothers reported significantly less control over their children's intake, and this was seen for both first‐born and second‐born twins. Twin analyses showed that these differences were not in response to children's genetic propensities, because monozygotic correlations were no greater than dizygotic correlations for maternal feeding style. Discussion: These results suggest that the stereotype of the obese mother, who uses food in nonnutritive ways so that her child also becomes obese, is more likely to be myth than fact. However, the results raise the possibility that lack of control of food intake might contribute to the emergence of differences in weight.