The interplay of leukemia cells and the bone marrow microenvironment

The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models have advanced our comprehension of leukemia-microenvironment crosstalk and have potential implications for development of novel treatment options

CO2, the greenhouse effect and global warming: from the pioneering work of Arrhenius and Callendar to today's Earth System Models

Climate warming during the course of the twenty-first century is projected to be between 1.0 and 3.7 °C depending on future greenhouse gas emissions, based on the ensemble-mean results of state-of-the-art Earth System Models (ESMs). Just how reliable are these projections, given the complexity of the climate system? The early history of climate research provides insight into the understanding and science needed to answer this question. We examine the mathematical quantifications of planetary energy budget developed by Svante Arrhenius (1859–1927) and Guy Stewart Callendar (1898–1964) and construct an empirical approximation of the latter, which we show to be successful at retrospectively predicting global warming over the course of the twentieth century. This approximation is then used to calculate warming in response to increasing atmospheric greenhouse gases during the twenty-first century, projecting a temperature increase at the lower bound of results generated by an ensemble of ESMs (as presented in the latest assessment by the Intergovernmental Panel on Climate Change). This result can be interpreted as follows. The climate system is conceptually complex but has at its heart the physical laws of radiative transfer. This basic, or “core” physics is relatively straightforward to compute mathematically, as exemplified by Callendar's calculations, leading to quantitatively robust projections of baseline warming. The ESMs include not only the physical core but also climate feedbacks that introduce uncertainty into the projections in terms of magnitude, but not sign: positive (amplification of warming). As such, the projections of end-of-century global warming by ESMs are fundamentally trustworthy: quantitatively robust baseline warming based on the well-understood physics of radiative transfer, with extra warming due to climate feedbacks. These projections thus provide a compelling case that global climate will continue to undergo significant warming in response to ongoing emissions of CO2 and other greenhouse gases to the atmosphere

Ecosystem Services and Disservices of Mangrove Forests and Salt Marshes

Coastal wetlands such as mangrove forests and salt marshes provide a range of important benefits to people, broadly defined as ecosystem services. These include provisioning services such as fuelwood and food, regulating services such as carbon sequestration and wave attenuation, and various tangible and intangible cultural services. However, strong negative perceptions of coastal wetlands also exist, often driven by the perceived or actual ecosystem disservices that they also produce. These can include odour, a sense of danger, and their real or perceived role in vector and disease transmission (e.g. malaria). This review provides an introduction to the ecosystem services and disservices concepts and highlights the broad range of services and disservices provided by mangrove forests and salt marshes. Importantly, we discuss the key implications of ecosystem services and disservices for the management of these coastal ecosystems. Ultimately, a clear binary does not exist between ecosystem services and disservices; an ecosystem service to one stakeholder can be viewed as a disservice to another, or a service can change seasonally into a disservice, and vice versa. It is not enough to only consider the beneficial ecosystem services that coastal wetlands provide: instead, we need to provide a balanced view of coastal wetlands that incorporates the complexities that exist in how humans relate to and interact with them

Scenario and modelling uncertainty in global mean temperature change derived from emission-driven global climate models

We compare future changes in global mean temperature in response to different future scenarios which, for the first time, arise from emission-driven rather than concentration-driven perturbed parameter ensemble of a global climate model (GCM). These new GCM simulations sample uncertainties in atmospheric feedbacks, land carbon cycle, ocean physics and aerosol sulphur cycle processes. We find broader ranges of projected temperature responses arising when considering emission rather than concentration-driven simulations (with 10–90th percentile ranges of 1.7 K for the aggressive mitigation scenario, up to 3.9 K for the high-end, business as usual scenario). A small minority of simulations resulting from combinations of strong atmospheric feedbacks and carbon cycle responses show temperature increases in excess of 9 K (RCP8.5) and even under aggressive mitigation (RCP2.6) temperatures in excess of 4 K. While the simulations point to much larger temperature ranges for emission-driven experiments, they do not change existing expectations (based on previous concentration-driven experiments) on the timescales over which different sources of uncertainty are important. The new simulations sample a range of future atmospheric concentrations for each emission scenario. Both in the case of SRES A1B and the Representative Concentration Pathways (RCPs), the concentration scenarios used to drive GCM ensembles, lies towards the lower end of our simulated distribution. This design decision (a legacy of previous assessments) is likely to lead concentration-driven experiments to under-sample strong feedback responses in future projections. Our ensemble of emission-driven simulations span the global temperature response of the CMIP5 emission-driven simulations, except at the low end. Combinations of low climate sensitivity and low carbon cycle feedbacks lead to a number of CMIP5 responses to lie below our ensemble range. The ensemble simulates a number of high-end responses which lie above the CMIP5 carbon cycle range. These high-end simulations can be linked to sampling a number of stronger carbon cycle feedbacks and to sampling climate sensitivities above 4.5 K. This latter aspect highlights the priority in identifying real-world climate-sensitivity constraints which, if achieved, would lead to reductions on the upper bound of projected global mean temperature change. The ensembles of simulations presented here provides a framework to explore relationships between present-day observables and future changes, while the large spread of future-projected changes highlights the ongoing need for such work

Poorest countries experience earlier anthropogenic emergence of daily temperature extremes

Understanding how the emergence of the anthropogenic warming signal from the noise of internal variability translates to changes in extreme event occurrence is of crucial societal importance. By utilising simulations of cumulative carbon dioxide (CO2) emissions and temperature changes from eleven earth system models, we demonstrate that the inherently lower internal variability found at tropical latitudes results in large increases in the frequency of extreme daily temperatures (exceedances of the 99.9th percentile derived from pre-industrial climate simulations) occurring much earlier than for mid-to-high latitude regions. Most of the world's poorest people live at low latitudes, when considering 2010 GDP-PPP per capita; conversely the wealthiest population quintile disproportionately inhabit more variable mid-latitude climates. Consequently, the fraction of the global population in the lowest socio-economic quintile is exposed to substantially more frequent daily temperature extremes after much lower increases in both mean global warming and cumulative CO2 emissions

The timing of anthropogenic emergence in simulated climate extremes

Determining the time of emergence of climates altered from their natural state by anthropogenic influences can help inform the development of adaptation and mitigation strategies to climate change. Previous studies have examined the time of emergence of climate averages. However, at the global scale, the emergence of changes in extreme events, which have the greatest societal impacts, has not been investigated before. Based on state-of-the-art climate models, we show that temperature extremes generally emerge slightly later from their quasi-natural climate state than seasonal means, due to greater variability in extremes. Nevertheless, according to model evidence, both hot and cold extremes have already emerged across many areas. Remarkably, even precipitation extremes that have very large variability are projected to emerge in the coming decades in Northern Hemisphere winters associated with a wettening trend. Based on our findings we expect local temperature and precipitation extremes to already differ significantly from their previous quasi-natural state at many locations or to do so in the near future. Our findings have implications for climate impacts and detection and attribution studies assessing observed changes in regional climate extremes by showing whether they will likely find a fingerprint of anthropogenic climate change

Quantifying exposure biases in early instrumental land surface air temperature observations

Exposure biases are a pervasive non-climatic change in land air temperature records which have been introduced as a result of changes in the way thermometers were sheltered from solar radiation and the elements over time. Exposure biases have not been widely accounted for in observational records, due to difficulties detecting/correcting the bias using traditional homogenisation techniques; therefore, exposure biases still contribute significant uncertainty to the early period in global temperature compilations. Here, an empirical approach to address the bias arising from the introduction of Stevenson-type screens from the late-19th century is presented. The approach consists of: (1) an empirical analysis of 54 parallel measurement series to identify the characteristics of the exposure bias in four exposure classes; (2) the development of bias-estimation models based on an analysis of which variables influence the bias; and (3) the application of the models to an extended version of CRUTEM5 (CRUTEM5_ext), based on exposure metadata, to quantify and reduce the bias. Step one identified differences between the temperatures recorded in Stevenson screens and early exposures, which vary seasonally, diurnally, and with location and exposure class. The largest biases (in mean temperatures) were found in freestanding exposures (up to −0.78°C annually) and in summer, while the smallest biases were generally found in wall-mounted exposures (near-0°C annually) and in winter. Significant relationships between the bias and temperature, downward top of atmosphere and/or received shortwave downward solar radiation were found in each exposure class and led to the development of three regression-based bias-estimation models. Application of these models to 1,960 mid-latitude stations in CRUTEM5_ext, resulted in small (≤0.016°C) positive adjustments to the Northern Hemisphere mid-latitude mean before 1880, and larger (≤−0.1°C) negative adjustments to the Northern and Southern Hemisphere mid-latitude means between 1882–1934 and 1856–1900, respectively. Larger adjustments were estimated regionally: up to −0.57°C annually and −0.79°C seasonally in individual grid cells

Seasonal cycles enhance disparities between low- and high-income countries in exposure to monthly temperature emergence with future warming

A common proxy for the adaptive capacity of a community to the impacts of future climate change is the range of climate variability which they have experienced in the recent past. This study presents an interpretation of such a framework for monthly temperatures. Our results demonstrate that emergence into genuinely 'unfamiliar' climates will occur across nearly all months of the year for low-income nations by the second half of the 21st century under an RCP8.5 warming scenario. However, high income countries commonly experience a large seasonal cycle, owing to their position in the middle latitudes: as a consequence, temperature emergence for transitional months translates only to more-frequent occurrences of heat historically associated with the summertime. Projections beyond 2050 also show low-income countries will experience 2–10 months per year warmer than the hottest month experienced in recent memory, while high-income countries will witness between 1–4 months per year hotter than any month previously experienced. While both results represent significant departures that may bring substantive societal impacts if greenhouse gas emissions continue unabated, they also demonstrate that spatial patterns of emergence will compound existing differences between high and low income populations, in terms of their capacity to adapt to unprecedented future temperatures

Towards seasonal Arctic shipping route predictions

The continuing decline in Arctic sea-ice will likely lead to increased human activity and opportunities for shipping in the region, suggesting that seasonal predictions of route openings will become ever more important. Here we present results from a set of 'perfect model' experiments to assess the predictability characteristics of the opening of Arctic sea routes. We find skilful predictions of the upcoming summer shipping season can be made from as early as January, although typically forecasts show lower skill before a May 'predictability barrier'. We demonstrate that in forecasts started from January, predictions of route opening date are twice as uncertain as predicting the closing date and that the Arctic shipping season is becoming longer due to climate change, with later closing dates mostly responsible. We find that predictive skill is state dependent with predictions for high or low ice years exhibiting greater skill than medium ice years. Forecasting the fastest open water route through the Arctic is accurate to within 200 km when predicted from July, a six-fold increase in accuracy compared to forecasts initialised from the previous November, which are typically no better than climatology. Finally we find that initialisation of accurate summer sea-ice thickness information is crucial to obtain skilful forecasts, further motivating investment into sea-ice thickness observations, climate models, and assimilation systems

The passive biomechanics of human pelvic collecting lymphatic vessels

The lymphatic system has a major significance in the metastatic pathways in women’s cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport