Energy and material flows of megacities

Understanding the drivers of energy and material flows of cities is important for addressing global environmental challenges. Accessing, sharing, and managing energy and material resources is particularly critical for megacities, which face enormous social stresses because of their sheer size and complexity. Here we quantify the energy and material flows through the world’s 27 megacities with populations greater than 10 million people as of 2010. Collectively the resource flows through megacities are largely consistent with scaling laws established in the emerging science of cities. Correlations are established for electricity consumption, heating and industrial fuel use, ground transportation energy use, water consumption, waste generation, and steel production in terms of heating-degree-days, urban form, economic activity, and population growth. The results help identify megacities exhibiting high and low levels of consumption and those making efficient use of resources. The correlation between per capita electricity use and urbanized area per capita is shown to be a consequence of gross building floor area per capita, which is found to increase for lower-density cities. Many of the megacities are growing rapidly in population but are growing even faster in terms of gross domestic product (GDP) and energy use. In the decade from 2001–2011, electricity use and ground transportation fuel use in megacities grew at approximately half the rate of GDP growth.The remarkable growth of cities on our planet during the past century has provoked a range of scientific inquires. From 1900–2011, the world’s urban population grew from 220 million (13% of the world’s population) to 3,530 million (52% of the world’s population) (1, 2). This phenomenon of urbanization has prompted the development of a science of cities (3, 4), including interdisciplinary contributions on scaling laws (5, 6), networks (7), and the thermodynamics of cities (8, 9). The growth of cities also has been strongly linked to global challenges of environmental sustainability, making the study of urban energy and material flows, e.g., for determining greenhouse gas emissions from cities and urban resource efficiency (10–19), important.At the pinnacle of the growth of cities is the formation of megacities, i.e., metropolitan regions with populations in excess of 10 million people. In 1970, there were only eight megacities on the planet (SI Appendix, Fig. S1). By 2010, the number had grown to 27, and a further 10 megacities likely will exist by 2020 (20). In 2010, 460 million people (6.7% of the global population) lived in the 27 megacities. The sheer size and complexity of megacities gives rise to enormous social and environmental challenges. Megacities often are perceived to be areas of high global risk (i.e., threatened by economic, environmental, geopolitical, societal, and technological risks with potential impacts across entire countries) with extreme levels of poverty, vulnerability, and social–spatial fragmentation (21–24). To provide adequate water and wastewater services, many megacities require massive technical investment and appropriate institutional development (25, 26). Many inhabitants of megacities also suffer severe health impacts from air pollution (27). However, these factors present only one side; the megacities include some of the wealthiest cities in the world (albeit with large disparities between citizens). Even the poorer megacities are seen by some as potential centers of innovation, where high levels of resource efficiency might reduce global environmental burdens (21, 28, 29). Whether megacities can develop as sustainable cities depends to a large extent on how they obtain, share, and manage their energy and material resources.The aims of our study are first to quantify the energy and material flows for the world’s 27 megacities, based on 2010 population, and second to identify physical and economic characteristics that underlie these resource flows at multiple scales. This goal entailed developing a common data-collection process applied to all the megacities. The cities were identified based on Brinkhoff’s database of metropolitan regions (www.citypopulation.de/world/Agglomerations.html; SI Appendix, Fig. S2). The megacities are essentially common commuter-sheds of more than 10 million people; most are contiguous urban regions, but a contiguous area is not a requirement; for example, the London megacity includes a ring of commuter towns outside the Greater London area. Megacities can spread across political borders. They include large tracts of suburban regions, which can have higher per capita resource flows than central areas (30, 31). We quantify energy flows for the dominant direct forms of consumption in megacities. A wide and complex range of materials flow through cities; here the focus is on water, concrete, steel, and waste. We show how values of aggregate resource use of all megacities generally are consistent with the scaling laws that have been developed for cities (5, 6). We then analyze factors correlated with energy and material flow at macro- and microscales; discuss megacities with low, high, and efficient use of resources; and examine changes over time.     

Life time fatality risk assessment due to variation of indoor radon concentration in dwellings in western Haryana, India

Indoor radon measurements in 60 dwellings belonging to 12 villages of Sirsa, Fatehbad and Hisar districts of western Haryana, India, have been carried out, using LR-115 type II cellulose nitrate films in the bare mode. The annual average indoor radon value in the studied area varies from 76.00 to 115.46 Bq m(-3), which is well within the recommended action level 200-300 Bq m(-3) (ICRP, 2009). The winter/summer ratio of indoor radon ranges from 0.78 to 2.99 with an average of 1.52. The values of annual average dose received by the residents and Life time fatality risk assessment due to variation of indoor radon concentration in dwellings of studied area suggests that there is no significance threat to the human beings due to the presence of natural radon in the dwellings.     

Inclusion of Compliance and Persistence in Economic Models

Economic models are developed to provide decision makers with information related to the real-world effectiveness of therapeutics, screening and diagnostic regimens. Although compliance with these regimens often has a significant impact on real-world clinical outcomes and costs, compliance and persistence have historically been addressed in a relatively superficial fashion in economic models. In this review, we present a discussion of the current state of economic modelling as it relates to the consideration of compliance and persistence. We discuss the challenges associated with the inclusion of compliance and persistence in economic models and provide an in-depth review of recent modelling literature that considers compliance or persistence, including a brief summary of previous reviews on this topic and a survey of published models from 2005 to 2012. We review the recent literature in detail, providing a therapeutic-area-specific discussion of the approaches and conclusions drawn from the inclusion of compliance or persistence in economic models. In virtually all publications, variation of model parameters related to compliance and persistence was shown to have a significant impact on predictions of economic outcomes. Growing recognition of the importance of compliance and persistence in the context of economic evaluations has led to an increasing number of economic models that consider these factors, as well as the use of more sophisticated modelling techniques such as individual simulations that provide an avenue for more rigorous consideration of compliance and persistence than is possible with more traditional methods. However, we note areas of continuing concern cited by previous reviews, including inconsistent definitions, documentation and tenuous assumptions required to estimate the effect of compliance and persistence. Finally, we discuss potential means to surmount these challenges via more focused efforts to collect compliance and persistence data.     

Dendritic cell paucity in mismatch repair–proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy

Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair–proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment in recent years. Anti–PD1 (anti–programmed cell-death protein 1) and anti–CTLA-4 (anti–cytotoxic T lymphocyte-associated protein 4) are two main types of ICB therapies that can be particularly effective (1). Metastatic melanoma, which was previously an incurable disease, now has cure rates of more than 50% when patients are treated with a combination of anti–PD1 and anti–CTLA-4 (2). However, ICB therapy is only effective in less than 15% of patients who receive the therapy (3), and efforts are ongoing to uncover the underlying mechanisms of intrinsic and acquired resistance.Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States (4) and in the world (5). Metastatic spread, especially to the liver, is a major cause of mortality in patients with CRC (6). The efficacy of ICB therapy in metastatic CRCs has been limited to patients with mismatch repair–deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, where a 55% objective response rate has been achieved (7). However, dMMR or MSI-H metastatic CRCs represent only about 5% of total metastatic CRC cases. The remaining 95% are mismatch repair–proficient (pMMR) or microsatellite stable (MSS) tumors (8), which are typically unresponsive to ICB therapy (8). Therefore, there is an urgent need to better understand the resistance mechanisms in pMMR and MSS metastatic CRCs, and improve the efficacy of treatments against this disease.Preclinical mouse models of cancer are effective tools for studying and improving cancer therapy. MC38 and CT26 are syngeneic mouse CRC cell lines commonly used in preclinical immunocompetent mouse models of cancer. In most preclinical studies, these cells are injected under the skin into the hind flank of mice, where they grow as subcutaneous tumors. When treated with ICB therapies such as anti–PD1 and/or anti–CTLA-4, these tumors have been shown to respond well (9, 10). However, MC38 and CT26 lack coding somatic mutations in the DNA mismatch repair genes and should be considered as pMMR CRC cell lines (11, 12). Hence, experimental preclinical models using subcutaneously implanted pMMR CRC cell lines fail to recapitulate the disease resistance to ICB therapy that is observed in patients.We hypothesized that orthotopic pMMR CRC mouse models, where pMMR CRC cells are implanted in the colon to represent primary colon tumors or in the liver to represent liver metastases, would more accurately recapitulate progression of the human disease and its response to ICB treatment in the clinic. Indeed, we report here strikingly different sensitivities to ICB treatment for pMMR CRC tumors grown orthotopically when compared with their subcutaneous counterparts. We further take advantage of these differences to define local nonmalignant components that determine the sensitivity of pMMR CRCs to treatment.