Population-level Differences Research Articles

Land-dependent marine species face climate-driven impacts on land and at sea

Land-dependent marine species are a unique guild of species whose life histories rely on both land and sea. This group is exposed to climate change-related stressors 2-fold, as climate change impacts likely occur at different velocities across land and sea habitat, leading to a greater probability of evolutionary traps. Thus, it is difficult to assess vulnerability and subsequently manage these populations in response to climate change. Without consideration of the factors unique to land-dependent marine species, current vulnerability assessment frameworks may fall short when evaluating climate impacts on these species. We identified commonalities in climate-related threats across taxa and geographic regions, highlighting the specific life history strategies that may be better suited to adapt to the changing climate. Accordingly, we suggest 3 considerations for assessing the vulnerability of land-dependent marine species: (1) degree of specialization, (2) intraspecies population-level differences, and (3) non-climate stressors. Where possible, we suggest how the exclusion of this information in management and conservation planning may lead to less successful outcomes. Potential compounding impacts of multiple stressors puts this group at particular risk of population collapse when losing land and/or sea habitat and functionality. Each of these considerations should be included when assessing vulnerabilities to climate change, as well as in effective and proactive management responses.

Higher prevalence of stunting and poor growth outcomes in HIV-exposed uninfected than HIV-unexposed infants in Kenya.

With the growing population of HIV-exposed uninfected (HEU) children globally, it is important to determine population-level growth differences between HEU and HIV-unexposed uninfected (HUU) children. We analyzed data from a population-level survey enrolling mother-infant pairs attending 6-week and 9-month immunizations in 140 clinics across Kenya. Weight-for-age (WAZ), length-for-age (LAZ), head circumference-for-age (HCAZ) z-scores and underweight (WAZ < -2), stunting (LAZ < -2), and microcephaly (HCAZ < -2), were compared between HEU and HUU. Correlates of growth faltering and poor growth were assessed using generalized Poisson and linear regression models. Among 2457 infants, 456 (19%) were HEU. Among mothers living with HIV, 64% received antiretroviral therapy (ART) and 22% were on antiretroviral prophylaxis during pregnancy. At 9 months, 72% of HEU and 98% of HUU were breastfeeding. At 6 weeks, HEU had lower mean WAZ (-0.41 vs. -0.09; P < 0.001) and LAZ (-0.99 vs. -0.31; P = 0.001) than HUU. Stunting was higher in HEU than HUU at 6 weeks (34% vs. 18%, P < 0.001) and 9 months (20% vs. 10%, P < 0.001). In multivariable analyses, HEU had lower mean LAZ at 6 weeks (-0.67, 95% confidence interval [CI]: -1.07, -0.26) and 9 months (-0.57, 95% CI: -0.92, -0.21) and HEU had higher stunting prevalence (week-6 adjusted prevalence ratio [aPR]: 1.88, 95% CI: 1.35, 2.63; month-9 aPR: 2.10, 95% CI: 1.41, 3.13). HEU had lower mean head circumference (-0.49, 95% CI: -0.91, -0.07) and higher prevalence of microcephaly (aPR: 2.21, 95% CI: 1.11, 4.41) at 9 months. Despite high maternal ART coverage, HEU had poorer growth than HUU in this large population-level comparison. Optimizing breastfeeding practices in HEU may be useful to improve growth.

Aggressiveness of Spanish Isolates of Xylella fastidiosa to Almond Plants of Different Cultivars Under Greenhouse Conditions.

The aggressiveness of Spanish isolates of Xylella fastidiosa, representing different sequence types, were studied in almond plants of several cultivars by means of the dynamics of the population levels and symptoms, colonization and spread, and dose-effect relationships. Pathogen dynamics in almond plants under greenhouse conditions showed doubling times of 2.1 to 2.5 days during the exponential growth phase, with a maximum population size of about 35 days postinoculation (dpi). Differences in patterns in population dynamics were observed between sap and xylem tissue after the exponential growth, as population levels in the xylem tissue remained stable while viable cells in sap decreased. Population levels were higher in two upward zones than in the downward zone with respect to the inoculation area. The first symptoms were observed between 20 and 60 dpi, and disease severity increased over time at doubling times of 30 days, with a maximum observed at 120 dpi. Strains tested showed differences in population levels in the cultivars studied and were able to spread with different intensity from contaminated plant parts to new growing shoots after pruning. Two almond isolates showed different performance in dose-effect relationships when inoculated in cultivar Avijor. Whereas IVIA 5387.2 reached high population levels but showed high median effective dose (ED50) and minimal infective dose (MID) values, IVIA 5901.2 showed low population levels and low ED50 and MID values. This study has implications for the epidemiology of X. fastidiosa in almond crops, estimating doubling times of the pathogen in planta and of symptom development and showing differences in aggressiveness between strains.

Pharmacogenetic testing for adverse drug reaction prevention: systematic review of economic evaluations and the appraisal of quality matters for clinical practice and implementation

BackgroundGenetic testing has potential roles in identifying whether an individual would have risk of adverse drug reactions (ADRs) from a particular medicine. Robust cost-effectiveness results on genetic testing would be useful for clinical practice and policy decision-making on allocating resources effectively. This study aimed to update a systematic review on economic evaluations of pharmacogenetic testing to prevent ADRs and critically appraise the quality of reporting and sources of evidence for model input parameters.MethodsWe searched studies through Medline via PubMed, Scopus and CRD’s NHS Economic Evaluation up to October 2019. Studies investigating polymorphism-based pharmacogenetic testing, which guided drug therapies to prevent ADRs, using economic evaluation methods were included. Two reviewers independently performed data extraction and assessed the quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines and the quality of data sources using the hierarchy of evidence developed by Cooper et al.ResultsFifty-nine economic evaluations of pharmacogenetic testing to avoid drug-induced ADRs were found between 2002 and 2018. Cost-utility and cost-effectiveness analyses were the most common methods of economic evaluation of pharmacogenetic testing. Most studies complied with the CHEERS checklist, except for single study-based economic evaluations which did not report uncertainty analysis (78%). There was a lack of high-quality evidence not only for estimating the clinical effectiveness of pharmacogenetic testing, but also baseline clinical data. About 14% of the studies obtained clinical effectiveness data of testing from a meta-analysis of case-control studies with direct comparison, which was not listed in the hierarchy of evidence used.ConclusionsOur review suggested that future single study-based economic evaluations of pharmacogenetic testing should report uncertainty analysis, as this could significantly affect the robustness of economic evaluation results. A specific ranking system for the quality of evidence is needed for the economic evaluation of pharmacogenetic testing of ADRs. Differences in parameters, methods and outcomes across studies, as well as population-level and system-level differences, may lead to the difficulty of comparing cost-effectiveness results across countries.

Population level differences in overwintering survivorship of blue crabs (Callinectes sapidus): A caution on extrapolating climate sensitivities along latitudinal gradients.

Winter mortality can strongly affect the population dynamics of blue crabs (Callinectes sapidus) near poleward range limits. We simulated winter in the lab to test the effects of temperature, salinity, and estuary of origin on blue crab winter mortality over three years using a broad range of crab sizes from both Great South Bay and Chesapeake Bay. We fit accelerated failure time models to our data and to data from prior blue crab winter mortality experiments, illustrating that, in a widely distributed, commercially valuable marine decapod, temperature, salinity, size, estuary of origin, and winter duration were important predictors of winter mortality. Furthermore, our results suggest that extrapolation of a Chesapeake Bay based survivorship model to crabs from New York estuaries yielded poor fits. As such, the severity and duration of winter can impact northern blue crab populations differently along latitudinal gradients. In the context of climate change, future warming could possibility confer a benefit to crab populations near the range edge that are currently limited by temperature-induced winter mortality by shifting their range edge poleward, but care must be taken in generalizing from models that are developed based on populations from one part of the range to populations near the edges, especially for species that occupy large geographical areas.

Impact of climate change on global agricultural markets under different shared socioeconomic pathways

AbstractThis analysis quantifies changesin global agricultural markets for maize, rice, soybeans, and wheat due to yield changes triggered by climate change. The scenarios include four representative concentration pathways (RCP), five global climate models, three shared socioeconomic pathways (SSPs) capturing differences in population levels and economic growth, and enhanced CO‐fertilization. Yield projections incorporate the influence of SSPs on nitrogen application and agricultural technology. Depending on the SSP and comparing the RCP8.5 ensemble yields (with CO‐fertilization) to a no climate change scenario in 2050, price increases for maize (61.3%–80.9%), soybeans (36.7%–51.7%), and wheat (5.4%–11.1%) are observed. Large wheat producers in temperate regions expand wheat production under climate change. Rice benefits from CO fertilization resulting in a relatively uniform price decrease across scenarios of 19.5%–19.9%. Cropland expansion between 2015 and 2050 is lowest for the high economic growth scenario. Depending on the crop and region, there are significant reductions in production especially for maize. Absolute changes in trade patterns are most pronounced for wheat and least for rice. Using trade as a means to dampen the negative welfare effects of climate change will be important and so is economic growth.

Environmental correlates of exploratory behavior and anxiety in three African striped mouse (Rhabdomys) taxa occurring in different habitats and contexts.

Species or populations are locally adapted to the environments they occupy because of different selection pressures. Our study considers behavioral differences in rodents originating from environments with different levels of overhead cover. We investigated exploratory behavior and anxiety in 4 populations of the African striped mouse Rhabdomys, in South Africa, from different environments: R. pumilio from a semi-desert; R. bechuanae and R. d. dilectus, which were sympatric in the central grasslands; and another allopatric R. d. dilectus occurred in the northern grasslands. We tested all individuals in 5 standard laboratory tests: light-dark, startle response, open field and novel object tests, and the plus maze. In a principle components analysis, R. pumilio and the central grassland R. dilectus grouped together, and R. bechuanae and the allopatric R. dilectus grouped together, but there was some overlap between populations. Univariate analyses showed population-level differences in exploration and anxiety. R. pumilio and the central R. d. dilectus were more exploratory and less anxious than R. bechuanae and the allopatric R. d. dilectus. The behavior of R. pumilio (more exploratory and less anxious) reflects the open environments it occupies in nature, whereas the allopatric R. d. dilectus and R. bechuanae were less exploratory and more anxious reflecting the closed habitats they occupy. The similarity between R. pumilio and the central R. d. dilectus cannot be explained by habitat and might be related to the effects of coexistence between central grassland R. d. dilectus and R. bechuanae, which may potentially alter the behavior of one or both species. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Associations between dimensions of behaviour, personality traits, and mental-health during the COVID-19 pandemic in the United Kingdom

The COVID-19 pandemic (including lockdown) is likely to have had profound but diverse implications for mental health and well-being, yet little is known about individual experiences of the pandemic (positive and negative) and how this relates to mental health and well-being, as well as other important contextual variables. Here, we analyse data sampled in a large-scale manner from 379,875 people in the United Kingdom (UK) during 2020 to identify population variables associated with mood and mental health during the COVID-19 pandemic, and to investigate self-perceived pandemic impact in relation to those variables. We report that while there are relatively small population-level differences in mood assessment scores pre- to peak-UK lockdown, the size of the differences is larger for people from specific groups, e.g. older adults and people with lower incomes. Multiple dimensions underlie peoples’ perceptions, both positive and negative, of the pandemic’s impact on daily life. These dimensions explain variance in mental health and can be statistically predicted from age, demographics, home and work circumstances, pre-existing conditions, maladaptive technology use and personality traits (e.g., compulsivity). We conclude that a holistic view, incorporating the broad range of relevant population factors, can better characterise people whose mental health is most at risk during the COVID-19 pandemic.

Sibling Similarity in Education Across and Within Societies.

The extent to which siblings resemble each other measures the omnibus impact of family background on life chances. We study sibling similarity in cognitive skills, school grades, and educational attainment in Finland, Germany, Norway, Sweden, the United Kingdom, and the United States. We also compare sibling similarity by parental education and occupation within these societies. The comparison of sibling correlations across and within societies allows us to characterize the omnibus impact of family background on education across social landscapes. Across countries, we find larger population-level differences in sibling similarity in educational attainment than in cognitive skills and school grades. In general, sibling similarity in education varies less across countries than sibling similarity in earnings. Compared with Scandinavian countries, the United States shows more sibling similarity in cognitive skills and educational attainment but less sibling similarity in school grades. We find that socioeconomic differences in sibling similarity vary across parental resources, countries, and measures of educational success. Sweden and the United States show greater sibling similarity in educational attainment in families with a highly educated father, and Finland and Norway show greater sibling similarity in educational attainment in families with a low-educated father. We discuss the implications of our results for theories about the impact of institutions and income inequality on educational inequality and the mechanisms that underlie such inequality.

Chill coma onset and recovery fail to reveal true variation in thermal performance among populations of Drosophila melanogaster

Species from colder climates tend to be more chill tolerant regardless of the chill tolerance trait measured, but for Drosophila melanogaster, population-level differences in chill tolerance among populations are not always found when a single trait is measured in the laboratory. We measured chill coma onset temperature, chill coma recovery time, and survival after chronic cold exposure in replicate lines derived from multiple paired African and European D. melanogaster populations. The populations in our study were previously found to differ in chronic cold survival ability, which is believed to have evolved independently in each population pair; however, they did not differ in chill coma onset temperature and chill coma recovery time in a manner that reflected their geographic origins, even though these traits are known to vary with origin latitude among Drosophila species and are among the most common metrics of thermal tolerance in insects. While it is common practice to measure only one chill tolerance trait when comparing chill tolerance among insect populations, our results emphasise the importance of measuring more than one thermal tolerance trait to minimize the risk of missing real adaptive variation in insect thermal tolerance.

Dancing in the Rain: How Do Abiotic Conditions Influence Sexually Selected Behaviors in the White-Ruffed Manakin?

Tropical animals respond to rainfall in population-specific ways. In extremely wet regions, endotherms experience heavy rains as stressors with consequences for behavior and demography. Ultimately, such stressors can affect the relative strength of abiotic selection, reducing the scope for sexual selection, and other biotic sources of selection. We studied population-level differences in the response to rainfall of White-ruffed manakins (Corapipo altera) on the Caribbean slope of Costa Rica, a species having a lek mating system subject to strong sexual selection. Between 2008 and 2013, we studied reproductive behavior in a population inhabiting an extremely wet site; estimates of apparent survival were low, and the turnover of display courts and dominant males was high. Males also engaged in coordinated display, and sub-adult males practiced in the presence of adults. Over three breeding seasons (2017-2019), we studied a population of the same species at a site only 110 km away, but in a location receiving roughly half as much rain. We tested behavioral predictions of three alternative mechanisms-indirect abiotic effects, direct mortality effects, and direct behavioral effects-linking rainfall to sexual selection in these two populations. Data derived from over 4300 h of observations at 105 display sites revealed high interannual variation in nearly all response variables, including turnover of display sites, retention of alpha status, male display behavior, and time females spent assessing male display. Additionally, we detected spatial differences in drivers of display site turnover. Notably, age distribution of males was skewed toward older individuals at the drier location. Based on these findings, we infer that indirect abiotic effects on forest structure leading to display site transience and direct effects of mortality increasing turnover in the male population likely underlie links between rain and the spatial and temporal differences we documented. Our results are consistent with rain constituting an important source of abiotic selection for tropical endotherms and modulating the scope for sexual selection near the extremes of a species' hygric niche.

Mesophotic coral refuges following multiple disturbances

As coral populations on shallow reefs decline globally, mesophotic coral ecosystems (MCE) have been proposed as potential coral refugia from thermal, storm, and anthropogenic disturbances in the face of climate change. The current study assesses the refuge potential of MCEs in the U.S. Virgin Islands (USVI) for Montastraea cavernosa by extrapolating reproductive potential through depth-stratified coral loss following regional storm, disease, and bleaching perturbations. Fecundity of this depth-generalist coral from 4 to 40 m was measured histologically, and polyp, population, and total habitat fecundities were then extrapolated across the species’ depth range. The number of reproductively active female gonads per polyp and oocyte size experienced a significant, though small, decrease with depth, potentially due to energetic limitations. Notably, the population sex ratio was not different from 1:1 on shallow and mid-depth reefs, but it became significantly male-biased (3.6:1) at mesophotic depths. Population-level differences in oocyte production over depth were primarily driven by changes in coral cover and sex ratio. The large spatial extent of mesophotic reefs relative to shallow reefs in the USVI makes MCEs the primary contributor of oocytes, despite the reduced proportion of females at depth. Following Hurricanes Irma and Maria in 2017, the outbreak of Stony Coral Tissue Loss Disease in 2019, and a bleaching event in 2019, shallow and mid-depth M. cavernosa populations experienced severe coral cover declines. Shallow and mid-depth population fecundities were predicted to decline correspondingly. Coral cover in MCEs remained relatively stable following these largely shallow water perturbations, and predicted population and total habitat fecundities remained constant as well. Thus, MCEs in the USVI currently appear to be reproductive refuges for M. cavernosa, but the persistence of that refuge remains in question as disease perturbation begins to affect deeper reefs.

Predator- and competitor-induced responses in amphibian populations that evolved different levels of pesticide tolerance.

Exposure to agrochemicals can drive rapid phenotypic and genetic changes in exposed populations. For instance, amphibian populations living far from agriculture (a proxy for agrochemical exposure) exhibit low pesticide tolerance, but they can be induced to possess high tolerance following a sublethal pesticide exposure. In contrast, amphibian populations close to agriculture exhibit high, constitutive tolerance to pesticides. A recent study has demonstrated that induced pesticide tolerance appears to have arisen from plastic responses to predator cues. As a result, we might expect that selection for constitutive pesticide tolerance in populations near agriculture (i.e., genetic assimilation) will lead to the evolution of constitutive responses to natural stressors. Using 15 wood frog (Rana sylvatica) populations from across an agricultural gradient, we conducted an outdoor mesocosm experiment to examine morphological (mass, body length, and tail depth) and behavioral responses (number of tadpoles observed and overall activity) of tadpoles exposed to three stressor environments (no-stressor, competitors, or predator cues). We discovered widespread differences in tadpole traits among populations and stressor environments, but no population-by-environment interaction. Subsequent linear models revealed that population distance to agriculture (DTA) was occasionally correlated with tadpole traits in a given environment and with magnitudes of plasticity, but none of the correlations were significant after Bonferroni adjustment. The magnitudes of predator and competitor plasticity were never correlated with the magnitude of pesticide-induced plasticity that we documented in a companion study. These results suggest that while predator-induced plasticity appears to have laid the foundation for the evolution of pesticide-induced plasticity and its subsequent genetic assimilation, inspection of population-level differences in plastic responses show that the evolution of pesticide-induced plasticity has not had a reciprocal effect on the evolved plastic responses to natural stressors.

The Meaning of "Cause" in Genetics.

Causation has multiple distinct meanings in genetics. One reason for this is meaning slippage between two concepts of the gene: Mendelian and molecular. Another reason is that a variety of genetic methods address different kinds of causal relationships. Some genetic studies address causes of traits in individuals, which can only be assessed when single genes follow predictable inheritance patterns that reliably cause a trait. A second sense concerns the causes of trait differences within a population. Whereas some single genes can be said to cause population-level differences, most often these claims concern the effects of many genes. Polygenic traits can be understood using heritability estimates, which estimate the relative influences of genetic and environmental differences to trait differences within a population. Attempts to understand the molecular mechanisms underlying polygenic traits have been developed, although causal inference based on these results remains controversial. Genetic variation has also recently been leveraged as a randomizing factor to identify environmental causes of trait differences. This technique-Mendelian randomization-offers some solutions to traditional epidemiological challenges, although it is limited to the study of environments with known genetic influences.

Changes in student behaviors and policy opinion regarding E-cigarettes at a Kentucky University from 2014 to 2018.

The behaviors and opinions regarding e-cigarette use and campus policies prohibiting vaping vary greatly among college students nationally. Kentucky is one of the four U.S. states with the highest tobacco use prevalence, and characterizing e-cigarette use, trends and policy opinions among Kentucky undergraduates may inform interventions. To characterize population-level differences in e-cigarette-related behaviors and policy opinions among undergraduates from 2014 to 2018, results from two cross-sectional surveys (2014 and 2018) from a public regional university in south-central Kentucky were analyzed. Students from randomly selected undergraduate general studies courses completed a 5-minute in-class survey. Data were obtained from 514 and 519 respondents in 2014 and 2018, respectively. Mean age did not differ (19.9 and 20.1 years; p = 0.41) nor did class rank (p = 0.30) by survey year. Chi-square analysis indicated previous 30-day e-cigarette use was higher in 2018 than 2014 (28% vs. 18%; p < 0.001), and current cigarette use was lower in 2018 than 2014 (13% vs. 25%; p < 0.001). When current smoking and recent e-cigarette use were combined as a use variable, there was no significant difference between 2018 (29%) and 2014 (30%). Fraternity/sorority affiliation, being under 22 years old, male gender, out-of-state residency, and having a smoking parent were associated with recent e-cigarette use in multivariable logit models. Support for the on-campus vaping prohibition was lower among 2018 respondents (68% approval) compared to 2014 respondents (74% approval), respectively (p = 0.022). Overall, these findings may inform policy, population-specific health communications, and future research.

Climate-driven flyway changes and memory-based long-distance migration.

Millions of migratory birds occupy seasonally favourable breeding grounds in the Arctic1, but we know little about the formation, maintenance and future of the migration routes of Arctic birds and the genetic determinants of migratory distance. Here we established a continental-scale migration system that used satellite tracking to follow 56peregrine falcons (Falco peregrinus) from 6populations that breed in the Eurasian Arctic, and resequenced 35genomes from 4of these populations. The breeding populations used five migration routes across Eurasia, which were probably formed by longitudinal and latitudinal shifts in their breeding grounds during the transition from the Last Glacial Maximum to the Holocene epoch. Contemporary environmental divergence between the routes appears to maintain their distinctiveness. We found that the gene ADCY8 is associated with population-level differences in migratory distance. We investigated the regulatory mechanism of this gene, and found that long-term memory was the most likely selective agent for divergence in ADCY8 among the peregrine populations. Global warming is predicted to influence migration strategies and diminish the breeding ranges of peregrine populations of the Eurasian Arctic. Harnessing ecological interactions and evolutionary processes to study climate-driven changes in migration can facilitate the conservation of migratory birds.

Intraspecific variation of reproductive traits between migratory and resident populations of the rice plant skipper Parnara guttata guttata

Much empirical data obtained across taxa is necessary to evaluate how variation in migratory costs and benefits can play a role in shaping the phenotypic and genetic patterns of reproductive investment between populations. Reproductive resources are allocated to both the size and number of eggs, and females may vary their allocation to each of these traits in response to increased movement capacity. In central regions of Japan, the rice plant skipper Parnara guttata guttata migrates in a southwesterly direction every year during late summer and early autumn (‘migratory’ population), but this migration is not observed in populations in southern or parts of western Japan (‘resident’ population). If migratory costs and benefits vary between these populations, they may cause their reproductive strategies to differ. Moreover, migration combined with a shift of reproductive allocation that evolved in one generation may influence the flight ability and patterns of reproductive allocation in the other generation in which migration has not evolved. In this study, a common-garden experiment was conducted to compare reproductive traits (egg size and number of eggs), flight ability and body size between these populations under two daylength regimes, at which different forms of adult P. g. guttata emerge. Under both daylength regimes the female adults of migratory populations had greater flight ability and tended to lay a greater number of eggs, which were on average smaller than the eggs laid by resident population females. A population-level difference in reaction norm elevation for flight ability and number of eggs was detected, but no interactions between population and daylength. The effects of the energetic cost of flight, adaptive constraints (e.g., genetic correlations and trade-offs), and the optimal strategy may explain the difference between populations of this species in the patterns of reproductive allocation to egg size and number of eggs.

Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology.

Simple SummaryGlioblastomas (GBMs) are the most frequent and aggressive malignant tumors arising in the human brain. One of the main reasons for GBM aggressiveness is its diverse cellular composition, comprised by differentiated tumor cells, tumor stem cells, cells from the blood vessels, and inflammatory cells, which simultaneously affect multiple cellular functions involved in cancer development. “Tumor Heterogeneity” usually encompasses both inter-tumor heterogeneity, differences observed at population level; and intra-tumor heterogeneity, differences among cells within individual tumors, which directly affect outcomes and response to treatment. In this review, we briefly describe the evolution of GBM classification yielded from inter-tumor heterogeneity studies and discuss how the technological development allows for the characterization of intra-tumor heterogeneity, beginning with differences based on histopathological features of GBM until the molecular alterations in DNA, RNA, and proteins observed at individual cells.One of the main reasons for the aggressive behavior of glioblastoma (GBM) is its intrinsic intra-tumor heterogeneity, characterized by the presence of clonal and subclonal differentiated tumor cell populations, glioma stem cells, and components of the tumor microenvironment, which affect multiple hallmark cellular functions in cancer. “Tumor Heterogeneity” usually encompasses both inter-tumor heterogeneity (population-level differences); and intra-tumor heterogeneity (differences within individual tumors). Tumor heterogeneity may be assessed in a single time point (spatial heterogeneity) or along the clinical evolution of GBM (longitudinal heterogeneity). Molecular methods may detect clonal and subclonal alterations to describe tumor evolution, even when samples from multiple areas are collected in the same time point (spatial-temporal heterogeneity). In GBM, although the inter-tumor mutational landscape is relatively homogeneous, intra-tumor heterogeneity is a striking feature of this tumor. In this review, we will address briefly the inter-tumor heterogeneity of the CNS tumors that yielded the current glioma classification. Next, we will take a deeper dive in the intra-tumor heterogeneity of GBMs, which directly affects prognosis and response to treatment. Our approach aims to follow technological developments, allowing for characterization of intra-tumor heterogeneity, beginning with differences on histomorphology of GBM and ending with molecular alterations observed at single-cell level.

The Option Value of Vacant Land: Don't Build when Demand for Housing Is Booming

Urban structures and urban growth rates are highly persistent. This has far-reaching implications for the optimal size and timing of new construction. We prove that rational developers postpone construction not because prospects are gloomy, but because they are bright. The slow mean reversion in urban growth rates for the Netherlands and the United States (estimated at ∼0.07 per annum) implies that a substantial share of cities should optimally postpone construction due to high growth. Observed heterogeneity in floorspace density across cities can be explained not by differences in population levels, but in growth rates.

Population level differences in overwintering survivorship of blue crabs (Callinectes sapidus): A caution on extrapolating climate sensitivities along latitudinal gradients

Population level differences in overwintering survivorship of blue crabs (Callinectes sapidus): A caution on extrapolating climate sensitivities along latitudinal gradients