Spatial quantitation of drugs in tissues using liquid extraction surface analysis mass spectrometry imaging

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported

External costs of atmospheric Pb emissions: valuation of neurotoxic impacts due to inhalation

<p>Abstract</p> <p>Background</p> <p>The Impact Pathway Approach (IPA) is an innovative methodology to establish links between emissions, related impacts and monetary estimates. Only few attempts have so far been presented regarding emissions of metals; in this study the external costs of airborne lead (Pb) emissions are assessed using the IPA. Exposure to Pb is known to provoke impacts especially on children's cognition. As cognitive abilities (measured as IQ, intelligence quotient) are known to have implications for lifetime income, a pathway can be established leading from figures for Pb emissions to the implied loss in earnings, and on this basis damage costs per unit of Pb emission can be assessed.</p> <p>Methods</p> <p>Different types of models are here linked. It is relatively straightforward to establish the relationship between Pb emissions and consequent increase in air-Pb concentration, by means of a Gaussian plume dispersion model (OML). The exposed population can then be modelled by linking the OML-output to population data nested in geo-referenced grid cells. Less straightforward is to establish the relationship between exposure to air-Pb concentrations and the resulting blood-Pb concentration. Here an Age-Dependent Biokinetic Model (ADBM) for Pb is applied. On basis of previous research which established links between increases in blood-Pb concentrations during childhood and resulting IQ-loss we arrive at our results.</p> <p>Results</p> <p>External costs of Pb airborne emissions, even at low doses, in our site are in the range of 41-83 €/kg emitted Pb, depending on the considered meteorological year. This estimate applies only to the initial effects of air-Pb, as our study does not address the effects due to the Pb environmental-accumulation and to the subsequent Pb re-exposure. These are likely to be between one and two orders of magnitude higher.</p> <p>Conclusions</p> <p>Biokinetic modelling is a novel tool not previously included when applying the IPA to explore impacts of Pb emissions and related external costs; it allows for more fine-tuned, age-dependent figures for the external costs from low-dose exposure. Valuation of additional health effects and impacts e.g. due to exposure via ingestion appear to be feasible when extending the insights from the present pilot study.</p

Micronutrient fortification of food and its impact on woman and child health: A systematic review

Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality

Sibling similarities and economic inequality in the US

Sibling correlation, Intergenerational mobility, J0, D3, J62,

Explaining explanations in AI

Recent work on interpretability in machine learning and AI has focused on the building of simplified models that approximate the true criteria used to make decisions. These models are a useful pedagogical device for teaching trained professionals how to predict what decisions will be made by the complex system, and most importantly how the system might break. However, when considering any such model it's important to remember Box's maxim that "All models are wrong but some are useful." We focus on the distinction between these models and explanations in philosophy and sociology. These models can be understood as a "do it yourself kit" for explanations, allowing a practitioner to directly answer "what if questions" or generate contrastive explanations without external assistance. Although a valuable ability, giving these models as explanations appears more difficult than necessary, and other forms of explanation may not have the same trade-offs. We contrast the different schools of thought on what makes an explanation, and suggest that machine learning might benefit from viewing the problem more broadly

The association of season and temperature with adverse pregnancy outcome in two German states, a time-series analysis.

BACKGROUND: A seasonality of low birth weight (LBW) and preterm birth (PTB) has been described for most regions and there is evidence that this pattern is caused by ambient outdoor temperature. However, the association as such, the direction of effect and the critical time of exposure remain controversial. METHODS: Logistic, time-series regression was performed on nearly 300,000 births from two German states to study the association between season and daily mean temperature and changes in daily proportions of term LBW (tLBW) or PTB. Analyses were adjusted for time-varying factors. Temperature exposures were examined during different periods of pregnancy. RESULTS: Weak evidence for an association between season of conception, season of birth or ambient outdoor temperature and tLBW or PTB was found. Results of analyses of temperature were not consistent between the two states. Different sources of bias which would have artificially led to stronger findings were detected and are described. CONCLUSIONS: No clear evidence for an association between season of conception, season of birth or temperature and tLBW or PTB was found. In the study of pregnancy outcome different sources of bias can be identified which can potentially explain heterogeneous findings of the past

Quantitative structural mechanobiology of platelet-driven blood clot contraction

Blood clot contraction is a cellular (patho)physiological process essential for wound healing, hemostasis, and thrombosis. Here, the authors describe the physical structural mechanism by which platelet filopodia pull “hand-over-hand” on fibrin fibers to compact them into bundled agglomerates