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Label-free chemical contrast is highly desirable in biomedical imaging. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. Here we report a three-dimensional multiphoton vibrational imaging technique based on stimulated Raman scattering (SRS). The sensitivity of SRS imaging is significantly greater than that of spontaneous Raman microscopy, which is achieved by implementing high-frequency (megahertz) phase-sensitive detection. SRS microscopy has a major advantage over previous coherent Raman techniques in that it offers background-free and readily interpretable chemical contrast. We show a variety of biomedical applications, such as differentiating distributions of omega-3 fatty acids and saturated lipids in living cells, imaging of brain and skin tissues based on intrinsic lipid contrast, and monitoring drug delivery through the epidermis.

We evaluate the impact of the 2009 Cash for Clunkers program on shortand medium-run auto purchases. Our empirical strategy exploits variation across U.S. cities in ex ante exposure to the program as measured by the number of \"clunkers\" in the city as of summer 2008. We find that the program induced the purchase of an additional 370,000 cars in July and August 2009. However, we find strong evidence of reversal; high clunker counties bought fewer autos in the 10 months after the program expired, which offset most of the initial purchases. We find no evidence of an effect on employment, house prices, or household default rates in cities with higher exposure to the program.

Clinical-grade T cells are genetically modified ex vivo to express chimeric antigen receptors (CARs) to redirect their specificity to target tumor-associated antigens in vivo. We now have developed this molecular strategy to render cytotoxic T cells specific for fungi. We adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ (designated “D-CAR”) upon binding with carbohydrate in the cell wall of Aspergillus germlings. T cells genetically modified with the Sleeping Beauty system to express D-CAR stably were propagated selectively on artificial activating and propagating cells using an approach similar to that approved by the Food and Drug Administration for manufacturing CD19-specific CAR ⁺ T cells for clinical trials. The D-CAR ⁺ T cells exhibited specificity for β-glucan which led to damage and inhibition of hyphal growth of Aspergillus in vitro and in vivo. Treatment of D-CAR ⁺ T cells with steroids did not compromise antifungal activity significantly. These data support the targeting of carbohydrate antigens by CAR ⁺ T cells and provide a clinically appealing strategy to enhance immunity for opportunistic fungal infections using T-cell gene therapy.

Imaging living organisms with molecular selectivity typically requires the introduction of specific labels. Many applications in biology and medicine, however, would significantly benefit from a noninvasive imaging technique that circumvents such exogenous probes. In vivo microscopy based on vibrational spectroscopic contrast offers a unique approach for visualizing tissue architecture with molecular specificity. We have developed a sensitive technique for vibrational imaging of tissues by combining coherent anti-Stokes Raman scattering (CARS) with video-rate microscopy. Backscattering of the intense forward-propagating CARS radiation in tissue gives rise to a strong epi-CARS signal that makes in vivo imaging possible. This substantially large signal allows for realtime monitoring of dynamic processes, such as the diffusion of chemical compounds, in tissues. By tuning into the CH2stretching vibrational band, we demonstrate CARS imaging and spectroscopy of lipid-rich tissue structures in the skin of a live mouse, including sebaceous glands, corneocytes, and adipocytes, with unprecedented contrast at subcellular resolution.

BackgroundExposure assessment represents a major challenge for studies on the relation between pesticides and health.ObjectiveWe developed a method combining information from crop-exposure matrices (CEMs) and land use data, in order to compute indices of environmental and occupational pesticide exposure. We illustrate our approach using French data (1979–2010).MethodsWe used CEMs for five crops (straw cereals, grain corn, corn fodder, potatoes, vineyards) that describe use (annual probability, frequency, intensity) of pesticide subgroups, chemical families, and active substances by region and time since 1960. We combined these data with land use data from agricultural censuses (1979, 1988, 2000, 2010) to compute indices of environmental and occupational pesticide exposure in cantons (small French administrative units). Indices of environmental exposure were calculated based on the area of each crop in the cantons, while indices of occupational exposure depended on combinations of crops in each farm from the cantons. To illustrate our approach, we selected a pesticide group (herbicides), chemical family of herbicides (phenoxyacetic acids), and active substance from the phenoxyacetic acids chemical family (2,4-D).ResultsThe estimated proportion of the area of crops with CEMs and of farms sprayed with herbicides was close to 100% between 1979–2010, but the estimated average annual number of applications increased. There were decreasing time-trends for phenoxyacetic acids and 2,4-D over the same period for all indices of exposure. There was a high use of herbicides throughout France in 2010, except in the South coast. For phenoxyacetic acids and 2,4-D, the spatial distribution was heterogeneous for all indices of exposure, with the highest values in the Centre and North regions.Impact statementAssessment of pesticide exposure is a key issue for epidemiological studies on their association with health outcomes. However, it presents some unique challenges, particularly for retrospective exposure and the investigation of chronic diseases. We present a method to compute indices of exposure by combining information from crop-exposure matrices for five crops and land use data. Specificities of environmental and occupational exposure are addressed using different methods. These methods are applied to pesticides used in agriculture in France for five crops (3 groups, 91 chemical families, 197 active substances) to produce indices at a small geographic scale from 1979 to 2010 for the whole metropolitan France. Besides using these indices in French epidemiological studies, our approach could be relevant for other countries.

Society recognises the importance of agriculture to supply goods, which are essential for human survival and well-being. Sustainable agriculture is an important goal since resources need to be preserved for future generations. The recent agricultural policy orientations towards environmental concerns have also had consequences for Portuguese agriculture. The information provided by the 2019 Agricultural Census offers an opportunity to analyse the recent dynamics and establish rankings of municipalities related to agricultural sustainability. Sustainability in agriculture can be studied using different types of indicators, but its quantification and aggregation into an index is still difficult. This paper proposes an approach based on compromise programming to analyse sustainability considering the dynamics between the 2009 and 2019 Agricultural Census. This approach has three main steps: in the first one, the indicators are selected and a HJ-Biplot and Cluster analysis are carried out to identify groups of municipalities and general dynamics; in the second step, the weights of indicators are defined, and a novel compromise programming model is implemented to define the rankings of sustainability for each year; finally, in the third step, the spatial dynamics of the sustainability rankings are analysed and classified into the clusters of municipalities previously created. The analysis was implemented using data from the 308 Portuguese municipalities for 12 individual indicators encompassing the several dimensions of sustainability. The results were promising since the approach allowed for the identification of the main dynamics and tendencies regarding sustainability.

Background Domestic and parental occupational pesticide exposures are suspected of involvement in the occurrence of childhood acute leukaemia (AL), but the role of exposure to agricultural activities is little known. In a previous ecological study conducted in France, we observed an increase in acute lymphoblastic leukaemia (ALL) incidence rate with increasing viticulture density in the municipalities of residence at diagnosis. Objectives This study aimed to test the hypothesis that residential proximity to croplands at birth increases the risk of childhood AL, with a particular focus on vineyards. Methods We identified all the primary AL cases diagnosed before the age of 15 years in the cohorts of children born in the French municipalities between 1990 and 2015. We estimated crop densities in each municipality of residence at birth using agricultural census data, for ten crop types. Variations in standardized incidence ratios (SIR) were evaluated with Poisson regression models, for all AL, ALL and acute myeloid leukaemia (AML), separately. Results Among the 19,809,700 children born and residing in mainland France at birth in 1990–2015, 8,747 AL cases (7,236 ALL and 1,335 AML) were diagnosed over the period. We did not evidence any statistically significant positive association between total crop density or any specific crop density in the municipality of residence at birth and all AL, ALL or AML. Interestingly, we observed a higher ALL incidence rate in the municipalities with the highest viticulture densities (SIR = 1.25 95%CI [1.01–1.54]). Adjusting for the main potential confounders did not change the results. Conclusion Our study does not support the hypothesis that residential proximity to croplands, particularly vineyards, around birth plays a role in childhood leukaemia. The slightly higher ALL incidence rate in children born in the municipalities with the highest viticulture densities may reflect the previously-observed association at diagnosis.

Agritourism and direct-to-consumer sales are increasingly used as diversification strategies to generate additional farm revenue streams. Yet despite their growing importance, the impacts, interactions, and adoption of these strategies remain poorly understood. Here we use univariate and bivariate local Moran’s I statistics to identify agritourism and direct-to-consumer sales hotspots in the United States and a Seemingly-Unrelated-Regression Spatial Durbin Model to examine the association between agritourism and direct farm sales to consumers. We find that agritourism and direct sales reinforce each other within the same county but not consistently across neighboring counties.

Better understanding of the fundamental mechanisms behind metabolic diseases requires methods to monitor lipid stores on single-cell level in vivo. We have used Caenorhabditis elegans as a model organism to demonstrate the limitations of fluorescence microscopy for imaging of lipids compared with coherent anti-Stokes Raman scattering (CARS) microscopy, the latter allowing chemically specific and label-free imaging in living organisms. CARS microscopy was used to quantitatively monitor the impact of genetic variations in metabolic pathways on lipid storage in 60 specimens of C. elegans. We found that the feeding-defective mutant pha-3 contained a lipid volume fraction one-third of that found in control worms. In contrast, mutants (daf-2, daf-4 dauer) with deficiencies in the insulin and transforming growth factors (IGF and TGF-β) signaling pathways had lipid volume fractions that were 1.4 and 2 times larger than controls, respectively. This was observed as an accumulation of small-sized lipid droplets in the hypodermal cells, hosting as much as 40% of the total lipid volume in contrast to the 9% for the wild-type larvae. Spectral CARS microscopy measurements indicated that this is accompanied by a shift in the ordering of the lipids from gel to liquid phase. We conclude that the degree of hypodermal lipid storage and the lipid phase can be used as a marker of lipid metabolism shift. This study shows that CARS microscopy has the potential to become a sensitive and important tool for studies of lipid storage mechanisms, improving our understanding of phenomena underlying metabolic disorders.

The ongoing climate crisis and growing water scarcity are exerting increasing pressure on agriculture in Southern and Western Europe, leading to reduced crop yields, greater risk of land abandonment, and deterioration of soil quality. Despite the extensive literature on irrigation and water use in agriculture, the specific relationship between irrigation availability and changes in the type of farming (ToF) remains insufficiently investigated. This study aims to address this gap by analyzing data from the 2010 and 2020 Italian General Agricultural Censuses conducted by ISTAT, in combination with microdata from the Italian Farm Accountancy Data Network (FADN), focusing on irrigated farms in Southern Italy. Descriptive analysis reveals that over 60% of irrigated farms specialize in permanent crops and predominantly adopt efficient irrigation systems such as drip irrigation. Between 2010 and 2020, approximately 23.8% of farms changed their ToF; however, these transitions were not generally associated with improvements in productivity or profitability. Results from logistic regression models suggest that structural variables—including Utilized Agricultural Area (UAA), economic size, and demographic characteristics such as the farmer’s gender—play a more significant role in determining changes in the ToF than the presence of irrigation itself. Moreover, the adoption of organic practices and larger farm sizes are positively associated with ToF changes. These findings suggest that while there has been some shift toward less water-demanding and potentially more sustainable crops, the impact of irrigation on such transitions remains limited. The results underscore the need for more targeted agricultural policies and improved data collection to support effective climate adaptation strategies in the sector.