Characterisation and traceability of extra virgin olive oil and table olive of Azapa variety marketed in Chile using Microsatellite Molecular Markers / Caracterización y trazabilidad de aceite de oliva virgen extra y aceituna de mesa de la variedad Azapa comercializados en Chile mediante marcadores moleculares microsatélites

Chile has two certified origin olive products: Extra-Virgin Olive Oil (EVOO) from Huasco valley and the Azapa variety table olive from the Azapa valley. However, efficient methodologies are needed to determine the varieties and raw materials involved in the end products. In this study, we assessed the size of alleles from ten microsatellites in 20 EVOOs and in leaves and fruits of 16 olive varieties cultivated in Chile to authenticate their origins. The identification of varieties relied on specific allele sizes derived from microsatellites markers UDO99-011 and DCA18-M found in leaves and fruit mesocarp. While most Chilean single-variety EVOOs matched the variety declared on the label, inconsistencies were observed in single-variety EVOOs containing multiple varieties. Our findings confirm that microsatellites serve as a valuable as diagnostic tools for ensuring the quality control of Geographical Indication certification for Azapa olives and EVOO with Designation of Origin from Huasco.

Chile cuenta con dos productos de oliva de origen certificado: El aceite de oliva virgen extra (AOVE) del valle del Huasco y la aceituna de mesa de la variedad Azapa del valle de Azapa. Sin embargo, se necesitan metodologías eficientes para determinar las variedades y materias primas involucradas en los productos finales. En este estudio, evaluamos el tamaño de los alelos de diez microsatélites en 20 AOVEs y en hojas y frutos de 16 variedades de aceituna cultivadas en Chile para autentificar sus orígenes. La identificación de las variedades se basó en los tamaños alélicos específicos derivados de los marcadores microsatélites UDO99-011 y DCA18-M encontrados en las hojas y el mesocarpio de los frutos. Aunque la mayoría de los AOVEs chilenos monovarietales coincidían con la variedad declarada en la etiqueta, se observaron incoherencias en los AOVEs monovarietales que contenían múltiples variedades. Nuestros hallazgos confirman que los microsatélites sirven como valiosas herramientas de diagnóstico para asegurar el control de calidad de la certificación de Indicación Geográfica para aceitunas de Azapa y AOVE con Denominación de Origen de Huasco.

Global arthropod beta-diversity is spatially and temporally structured by latitude.

Global biodiversity gradients are generally expected to reflect greater species replacement closer to the equator. However, empirical validation of global biodiversity gradients largely relies on vertebrates, plants, and other less diverse taxa. Here we assess the temporal and spatial dynamics of global arthropod biodiversity dynamics using a beta-diversity framework. Sampling includes 129 sampling sites whereby malaise traps are deployed to monitor temporal changes in arthropod communities. Overall, we encountered more than 150,000 unique barcode index numbers (BINs) (i.e. species proxies). We assess between site differences in community diversity using beta-diversity and the partitioned components of species replacement and richness difference. Global total beta-diversity (dissimilarity) increases with decreasing latitude, greater spatial distance and greater temporal distance. Species replacement and richness difference patterns vary across biogeographic regions. Our findings support long-standing, general expectations of global biodiversity patterns. However, we also show that the underlying processes driving patterns may be regionally linked.

Geographical variation in hotspots of stunting among under-five children in Ethiopia: A geographically weighted regression and multilevel robust Poisson regression analysis.

INTRODUCTION: Childhood stunting is a global public health concern, associated with both short and long-term consequences, including high child morbidity and mortality, poor development and learning capacity, increased vulnerability for infectious and non-infectious disease. The prevalence of stunting varies significantly throughout Ethiopian regions. Therefore, this study aimed to assess the geographical variation in predictors of stunting among children under the age of five in Ethiopia using 2019 Ethiopian Demographic and Health Survey. METHOD: The current analysis was based on data from the 2019 mini Ethiopian Demographic and Health Survey (EDHS). A total of 5,490 children under the age of five were included in the weighted sample. Descriptive and inferential analysis was done using STATA 17. For the spatial analysis, ArcGIS 10.7 were used. Spatial regression was used to identify the variables associated with stunting hotspots, and adjusted R2 and Corrected Akaike Information Criteria (AICc) were used to compare the models. As the prevalence of stunting was over 10%, a multilevel robust Poisson regression was conducted. In the bivariable analysis, variables having a p-value < 0.2 were considered for the multivariable analysis. In the multivariable multilevel robust Poisson regression analysis, the adjusted prevalence ratio with the 95% confidence interval is presented to show the statistical significance and strength of the association. RESULT: The prevalence of stunting was 33.58% (95%CI: 32.34%, 34.84%) with a clustered geographic pattern (Moran's I = 0.40, p<0.001). significant hotspot areas of stunting were identified in the west and south Afar, Tigray, Amhara and east SNNPR regions. In the local model, no maternal education, poverty, child age 6-23 months and male headed household were predictors associated with spatial variation of stunting among under five children in Ethiopia. In the multivariable multilevel robust Poisson regression the prevalence of stunting among children whose mother's age is >40 (APR = 0.74, 95%CI: 0.55, 0.99). Children whose mother had secondary (APR = 0.74, 95%CI: 0.60, 0.91) and higher (APR = 0.61, 95%CI: 0.44, 0.84) educational status, household wealth status (APR = 0.87, 95%CI: 0.76, 0.99), child aged 6-23 months (APR = 1.87, 95%CI: 1.53, 2.28) were all significantly associated with stunting. CONCLUSION: In Ethiopia, under-five children suffering from stunting have been found to exhibit a spatially clustered pattern. Maternal education, wealth index, birth interval and child age were determining factors of spatial variation of stunting. As a result, a detailed map of stunting hotspots and determinants among children under the age of five aid program planners and decision-makers in designing targeted public health measures.

Study on the differences and influencing factors of spatial distribution of population aging at township scale: a case study of township research units in Anshun City, China.

An aging population is one of the main features of China's current population structure, and it is a key area that needs attention to achieve high-quality population development. Because of its unique geographical environment, economic conditions, and sociocultural background, the study of population aging in the karst region of southwest China is particularly important. However, there is a lack of research exploring the regional differentiation of population aging and its influencing factors in the karst regions of southwest China. In light of this, we chose Anshun City, located in Guizhou Province's southwest area, as the case study area. We used the Lorenz curve and spatial autocorrelation to study the differences in the spatial distribution pattern of population aging and introduced multi-scale geographical weighted regression to explore its influencing factors. The results show that Anshun City's older people population proportion (OPP) is generally high with more than 7% of the older people there, making it part of an aging society. The OPP appeared high in the east and low in the west in spatial distribution; the older people population density (OPD) revealed a gradually increasing trend from south to north. At the township scale, both the OPP and the OPD showed significant spatial positive correlation, and the spatial agglomeration characteristics were obvious. OPD and OPP have a positive spatial correlation at the global level, and townships with similar OPP or OPD were spatially adjacent. The spatial distribution characteristics of population aging are the consequence of complex contributions such as natural, social, economic, and karst factors. Further, the spatial distribution pattern of aging is determined by a variety of influencing factors, which have different directions and intensities. Therefore, it is necessary to formulate and implement corresponding policies and strategies to deal with the aging problem in the future.

The geography of corporate fake news.

Although a rich academic literature examines the use of fake news by foreign actors for political manipulation, there is limited research on potential foreign intervention in capital markets. To address this gap, we construct a comprehensive database of (negative) fake news regarding U.S. firms by scraping prominent fact-checking sites. We identify the accounts that spread the news on Twitter (now X) and use machine-learning techniques to infer the geographic locations of these fake news spreaders. Our analysis reveals that corporate fake news is more likely than corporate non-fake news to be spread by foreign accounts. At the country level, corporate fake news is more likely to originate from African and Middle Eastern countries and tends to increase during periods of high geopolitical tension. At the firm level, firms operating in uncertain information environments and strategic industries are more likely to be targeted by foreign accounts. Overall, our findings provide initial evidence of foreign-originating misinformation in capital markets and thus have important policy implications.

Physiography, foraging mobility, and the first peopling of Sahul.

The route and speed of migration into Sahul by Homo sapiens remain a major research question in archaeology. Here, we introduce an approach which models the impact of the physical environment on human mobility by combining time-evolving landscapes with Lévy walk foraging patterns, this latter accounting for a combination of short-distance steps and occasional longer moves that hunter-gatherers likely utilised for efficient exploration of new environments. Our results suggest a wave of dispersal radiating across Sahul following riverine corridors and coastlines. Estimated migration speeds, based on archaeological sites and predicted travelled distances, fall within previously reported range from Sahul and other regions. From our mechanistic movement simulations, we then analyse the likelihood of archaeological sites and highlight areas in Australia that hold archaeological potential. Our approach complements existing methods and provides interesting perspectives on the Pleistocene archaeology of Sahul that could be applied to other regions around the world.

Tree water uptake patterns across the globe.

Plant water uptake from the soil is a crucial element of the global hydrological cycle and essential for vegetation drought resilience. Yet, knowledge of how the distribution of water uptake depth (WUD) varies across species, climates, and seasons is scarce relative to our knowledge of aboveground plant functions. With a global literature review, we found that average WUD varied more among biomes than plant functional types (i.e. deciduous/evergreen broadleaves and conifers), illustrating the importance of the hydroclimate, especially precipitation seasonality, on WUD. By combining records of rooting depth with WUD, we observed a consistently deeper maximum rooting depth than WUD with the largest differences in arid regions - indicating that deep taproots act as lifelines while not contributing to the majority of water uptake. The most ubiquitous observation across the literature was that woody plants switch water sources to soil layers with the highest water availability within short timescales. Hence, seasonal shifts to deep soil layers occur across the globe when shallow soils are drying out, allowing continued transpiration and hydraulic safety. While there are still significant gaps in our understanding of WUD, the consistency across global ecosystems allows integration of existing knowledge into the next generation of vegetation process models.

Temporal and geographical variations in diagnostic imaging in Norway.

BACKGROUND: Unwarranted temporal and geographical variations are acknowledged as a profound problem for equal access and justice in the provision of health services. Even more, they challenge the quality, safety, and efficiency of such services. This is highly relevant for imaging services. OBJECTIVE: To analyse the temporal and geographical variation in the number of diagnostic images in Norway from 2013 to 2021. METHODS: Data on outpatient imaging provided by the Norwegian Health Economics Administration (HELFO) and inpatient data afforded by fourteen hospital trusts and hospitals in Norway. Data include the total number of imaging examinations according to the Norwegian Classification of Radiological Procedures (NCRP). Analyses were performed with descriptive statistics. RESULTS: More than 37 million examinations were performed in Norway during 2013-2021 giving an average of 4.2 million examinations per year. In 2021 there was performed and average of 0.8 examinations per person and 2.2 examinations per person for the age group > 80. There was a 9% increase in the total number of examinations from 2013 to 2015 and a small and stable decrease of 0.5% per year from 2015 to 2021 (with the exception of 2020 due to the pandemic). On average 71% of all examinations were outpatient examinations and 32% were conducted at private imaging centres. There were substantial variations between the health regions, with Region South-East having 53.1% more examinations per inhabitant than Region West. The geographical variation was even more outspoken when comparing catchment areas, where Oslo University Hospital Trust had twice as many examinations per inhabitant than Finnmark Hospital Trust. CONCLUSION: As the population in Norway is homogeneous it is difficult to attribute the variations to socio-economic or demographic factors. Unwarranted and supply-sensitive variations are challenging for healthcare systems where equal access and justice traditionally are core values.

Recent Advances and Future Perspectives in the E-Nose Technologies Addressed to the Wine Industry.

Electronic nose devices stand out as pioneering innovations in contemporary technological research, addressing the arduous challenge of replicating the complex sense of smell found in humans. Currently, sensor instruments find application in a variety of fields, including environmental, (bio)medical, food, pharmaceutical, and materials production. Particularly the latter, has seen a significant increase in the adoption of technological tools to assess food quality, gradually supplanting human panelists and thus reshaping the entire quality control paradigm in the sector. This process is happening even more rapidly in the world of wine, where olfactory sensory analysis has always played a central role in attributing certain qualities to a wine. In this review, conducted using sources such as PubMed, Science Direct, and Web of Science, we examined papers published between January 2015 and January 2024. The aim was to explore prevailing trends in the use of human panels and sensory tools (such as the E-nose) in the wine industry. The focus was on the evaluation of wine quality attributes by paying specific attention to geographical origin, sensory defects, and monitoring of production trends. Analyzed results show that the application of E-nose-type sensors performs satisfactorily in that trajectory. Nevertheless, the integration of this type of analysis with more classical methods, such as the trained sensory panel test and with the application of destructive instrument volatile compound (VOC) detection (e.g., gas chromatography), still seems necessary to better explore and investigate the aromatic characteristics of wines.

Exponential growth of private coastal infrastructure influenced by geography and race in South Carolina, USA.

Homeowners in coastal environments often augment their access to estuarine ecosystems by building private docks on their personal property. Despite the commonality of docks, particularly in the Southeastern United States, few works have investigated their historical development, their distribution across the landscape, or the environmental justice dimensions of this distribution. In this study, we used historic aerial photography to track the abundance and size of docks across six South Carolina counties from the 1950s to 2016. Across our roughly 60-year study period, dock abundance grew by two orders of magnitude, mean length of newly constructed docks doubled, and the cumulative length of docks ballooned from 34 to 560 km. Additionally, we drew on census data interpolated into consistent 2010 tract boundaries to analyze the racial and economic distribution of docks in 1994, 1999, 2011, and 2016. Racial composition, measured as the percentage of a tract's population that was White, positively correlated with dock abundance in each year. Median household income and dock abundance were only correlated in 2011. Taken together, these metrics indicate the growing desire for direct estuary access, however, that access does not appear to be equally spread across racial groups. Because docks enhance estuarine access and demarcate private property, our study provides longitudinal insights into environmental justice concerns related to disparate private property ownership. We found a persistent correlation between the racial characteristics of an area and dock abundance, strongly indicating that White South Carolinians have had disproportionately greater private water access for the past two decades.

Discovering Subgroups of Children With High Mortality in Urban Guinea-Bissau: Exploratory and Validation Cohort Study.

BACKGROUND: The decline in global child mortality is an important public health achievement, yet child mortality remains disproportionally high in many low-income countries like Guinea-Bissau. The persisting high mortality rates necessitate targeted research to identify vulnerable subgroups of children and formulate effective interventions. OBJECTIVE: This study aimed to discover subgroups of children at an elevated risk of mortality in the urban setting of Bissau, Guinea-Bissau, West Africa. By identifying these groups, we intend to provide a foundation for developing targeted health interventions and inform public health policy. METHODS: We used data from the health and demographic surveillance site, Bandim Health Project, covering 2003 to 2019. We identified baseline variables recorded before children reached the age of 6 weeks. The focus was on determining factors consistently linked with increased mortality up to the age of 3 years. Our multifaceted methodological approach incorporated spatial analysis for visualizing geographical variations in mortality risk, causally adjusted regression analysis to single out specific risk factors, and machine learning techniques for identifying clusters of multifactorial risk factors. To ensure robustness and validity, we divided the data set temporally, assessing the persistence of identified subgroups over different periods. The reassessment of mortality risk used the targeted maximum likelihood estimation (TMLE) method to achieve more robust causal modeling. RESULTS: We analyzed data from 21,005 children. The mortality risk (6 weeks to 3 years of age) was 5.2% (95% CI 4.8%-5.6%) for children born between 2003 and 2011, and 2.9% (95% CI 2.5%-3.3%) for children born between 2012 and 2016. Our findings revealed 3 distinct high-risk subgroups with notably higher mortality rates, children residing in a specific urban area (adjusted mortality risk difference of 3.4%, 95% CI 0.3%-6.5%), children born to mothers with no prenatal consultations (adjusted mortality risk difference of 5.8%, 95% CI 2.6%-8.9%), and children from polygamous families born during the dry season (adjusted mortality risk difference of 1.7%, 95% CI 0.4%-2.9%). These subgroups, though small, showed a consistent pattern of higher mortality risk over time. Common social and economic factors were linked to a larger share of the total child deaths. CONCLUSIONS: The study's results underscore the need for targeted interventions to address the specific risks faced by these identified high-risk subgroups. These interventions should be designed to work to complement broader public health strategies, creating a comprehensive approach to reducing child mortality. We suggest future research that focuses on developing, testing, and comparing targeted intervention strategies unraveling the proposed hypotheses found in this study. The ultimate aim is to optimize health outcomes for all children in high-mortality settings, leveraging a strategic mix of targeted and general health interventions to address the varied needs of different child subgroups.

The Geography of Metacommunities: Landscape Characteristics Drive Geographic Variation in the Assembly Process through Selecting Species Pool Attributes.

AbstractThe nonrandom association between landscape characteristics and the dominant life history strategies observed in species pools is a typical pattern in nature. Here, we argue that these associations determine predictable changes in the relative importance of assembly mechanisms along broadscale geographic gradients (i.e., the geographic context of metacommunity dynamics). To demonstrate that, we employed simulation models in which groups of species with the same initial distribution of niche breadths and dispersal abilities interacted across a wide range of landscapes with contrasting characteristics. By assessing the traits of dominant species in the species pool in each landscape type, we determined how different landscape characteristics select for different life history strategies at the metacommunity level. We analyzed the simulated data using the same analytical approaches used in the study of empirical metacommunities to derive predictions about the causal relationships between landscape characteristics and dominant life histories in species pools, as well as their reciprocal influence on empirical inferences regarding the assembly process. We provide empirical support for these predictions by contrasting the assembly of moth metacommunities in a tropical versus a temperate mountainous landscape. Together, our model framework and empirical analyses demonstrate how the geographic context of metacommunities influences our understanding of community assembly across broadscale ecological gradients.

Propagation thresholds and driving mechanism detection of karst meteorological- agricultural drought: A case study in Guizhou Province.

It is significant to systematically quantify the propagation thresholds of meteorological drought to different levels of agricultural drought in karst areas, and revealit's the propagation driving mechanisms. This can guide early warning and fine management of agricultural drought. In this study,we selected Guizhou Province as an example. The standardized precipitation evapotranspiration index (SPEI) and standardized soil moisture index (SSI) were used to characterize meteorological and agricultural drought. The run theory was used to identify, merge and eliminate drought events. The maximum correlation coefficient was used to capture the propagation time of meteorological-agricultural drought. The regression models were used to quantify the propagation intensity threshold from meteorological drought to different levels of agricultural drought. Finally, the propagation threshold driving mechanism was explored using geographical detectors. The results show that: (1) in terms of temporal variations during the past 21 years, regional meteorological drought had a shorter duration and a higher intensity than agricultural drought, Particularly, 2011 was a year of severe drought, and agricultural drought was significantly alleviated after 2014. (2) In terms of spatial variations, the "long duration area" of meteorological drought duration showed an "S" shaped distribution in the northeast, and the "short duration area" showed a point-like distribution. The overall duration of agricultural drought showed a spatial distribution of northeast to "medium-high in the northeast and low in the southwest. (3) The drought propagation time showed an alternating distribution of "valley-peak-valley-peak" from southeast to northwest. In terms of propagation intensity thresholds, light drought showed an overall spatial distribution of high in the east and low in the west. Moderate, severe, and extreme droughts showed a spatial distribution of low in the center north of southern Guizhou) and high in the borders. (4) There was a strong spatial coupling relationship between karst development intensity, altitude and meteorological-agricultural drought propagation thresholds. The interaction of different factors exhibited a two-factor enhancement and nonlinear enhancement on the propagation threshold. This indicates that synergistic effects of different factors on the propagation threshold were larger than single-factor effects.

Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.

Aspects of public health development in China's western region.

The public health level in a country is closely related to national development and quality of life. In order to appraise the level of health services in the western region of China, panel data of 124 prefecture-level units covering the period 2011 to 2021 was used together with a health evaluation index system based on four dimensions: quality of life, environmental situation, the level of health services and longevity. To assess this, we used entropy weights, standard deviation and coefficient of variation together with the geographical detector model that measures the stratified spatial heterogeneity. The results show that although public health services have improved overall, the various dimensions are still not balanced as longevity did not match up everywhere. While the developmental level of the various health dimensions presents a pattern of a relatively smooth increasing gradient in the west-central- east direction, the situation with respect to the north-centralsouth is more uneven with both ups and downs. However, a trend of continuous enhancement of all health dimensions was found with a significant positive correlation of spatial clustering, with hotspots and 'sub-hotspots' contracting from north to south, while coldspots and 'sub-coldspots' expanded from west to east. This can be seen as the result of multiple factors, with the level of urbanization and economic level as the dominant factors and government guidance, agglomeration capacity and industrial structure being auxiliary.

Bringing traits back into the equation: A roadmap to understand species redistribution.

Ecological and evolutionary theories have proposed that species traits should be important in mediating species responses to contemporary climate change; yet, empirical evidence has so far provided mixed evidence for the role of behavioral, life history, or ecological characteristics in facilitating or hindering species range shifts. As such, the utility of trait-based approaches to predict species redistribution under climate change has been called into question. We develop the perspective, supported by evidence, that trait variation, if used carefully can have high potential utility, but that past analyses have in many cases failed to identify an explanatory value for traits by not fully embracing the complexity of species range shifts. First, we discuss the relevant theory linking species traits to range shift processes at the leading (expansion) and trailing (contraction) edges of species distributions and highlight the need to clarify the mechanistic basis of trait-based approaches. Second, we provide a brief overview of range shift-trait studies and identify new opportunities for trait integration that consider range-specific processes and intraspecific variability. Third, we explore the circumstances under which environmental and biotic context dependencies are likely to affect our ability to identify the contribution of species traits to range shift processes. Finally, we propose that revealing the role of traits in shaping species redistribution may likely require accounting for methodological variation arising from the range shift estimation process as well as addressing existing functional, geographical, and phylogenetic biases. We provide a series of considerations for more effectively integrating traits as well as extrinsic and methodological factors into species redistribution research. Together, these analytical approaches promise stronger mechanistic and predictive understanding that can help society mitigate and adapt to the effects of climate change on biodiversity.

Rapid discrimination of geographical origin of garlic (Allium sativum L.): A metabolomic approach applied to paper spray mass spectrometry data.

INTRODUCTION: Distinguishing and categorizing the origin of garlic are highly significant, considering its widespread use as a flavoring agent. With billions of dollars annually in global trade, garlic is frequently susceptible to fraudulent practices. METHODOLOGY: Paper spray ionization mass spectrometry (PS-MS) was employed to quickly analyze garlic samples from distinct geographic origins: China and Brazil. The so-generated PS-MS data were treated with metabolomic multivariate approaches, and the garlic samples from these different geographic regions were easily discriminated. RESULTS: Brazilian garlic was characterized to contain higher levels of amino acids, such as arginine, proline, and valine, and organosulfur compounds, such as allicin, alliin, and l-γ-glutamil-S-allyl-l-cysteine, compared to Chinese garlic. The PS-MS data were treated employing multivariate approaches, typically used in the metabolomics field, and this protocol was promptly able to discern among both types of samples. CONCLUSION: Hence, this combined strategy holds promise not only as an effective tool for the authentication of the geographical origin of garlic but also as a powerful means for biomarker discovery.