ResearchPad - special-feature https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Serum IgA Fc effector functions in infectious disease and cancer]]> https://www.researchpad.co/article/elastic_article_8248 The role of mucosal immunoglobulin A (IgA) in infection (e.g. neutralization) has been extensively investigated; by contrast, serum IgA is poorly understood. Crosslinking of serum IgA with fragment crystallizable alpha receptor I (FcαRI) can activate immune cells (e.g. phagocytosis, antibody‐dependent cellular cytotoxicity, reactive oxygen species) to clear select bacteria, viruses and tumors, whereas monomeric serum IgA can inhibit these functions hindering an effective immune response. Here we discuss serum IgA Fc effector functions in infectious disease and tumor clearance, potential applications in immunotherapy and limitations of current research.

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<![CDATA[Dielectric-induced surface wave radiation loss]]> https://www.researchpad.co/article/Nf744108f-3177-456a-9f7b-980cfcadf3d0 We investigate a model which shows how the introduction of a perturbing dielectric close to an electromagnetic surface wave leads to radiation away from the surface through the dielectric. This resembles a surface waveguide passing through a wall or being deployed underground. Our theory, which is based on the mode-matching technique, allows quantitative determination of losses from a bound surface wave mode up to the point of its complete extinction. For a surface wave supported by a coated, conducting sheet the attenuation due to the perturbing dielectric is calculated for a number of frequencies, permittivities of the perturbation and separations between the sheet and the perturbing dielectric. The accuracy of our results is verified by simulation of the system with a full-wave numerical solution. Finally, we report experimental data of perturbed surface waves on a cable, which are in qualitative agreement with our model.

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<![CDATA[First-line endocrine therapy for postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis]]> https://www.researchpad.co/article/Nafa61ea7-915c-447e-a790-256d21c722b9 In establishing the 2018 Breast Cancer Practice Guidelines of the Japan Breast Cancer Society, we explored the optimal first-line endocrine therapy for advanced postmenopausal hormone receptor-positive breast cancer.MethodsWe performed a systematic review of relevant reports from randomized-controlled studies published prior to November 2016 found using medical journal search engines. The main outcomes which we evaluated were progression-free survival (PFS), objective response rate (ORR), disease control rate (CBR), and toxicity.ResultsFour controlled trials comparing aromatase inhibitors (AI) and cyclin-dependent kinase (CDK)4/6 inhibitor combination therapy to AI monotherapy, and two controlled trials comparing anastrozole to fulvestrant 500 mg were analyzed. AI/CDK4/6 inhibitor combination therapy significantly improved PFS (Risk Ratio: 0.67, 95%CI 0.60–0.73), increased ORR (Risk Difference: 0.11, 95% CI 0.07–0.16), and increased CBR (Risk Difference: 0.11, 95% CI 0.07–0.15), compared with AI monotherapy. Patients who received this combination therapy had a higher grade ≥ 3 adverse event rate more than those who received AI monotherapy (Risk Difference: 43%, 95%CI: 0.39–0.47). Fulvestrant 500 mg alone significantly improved PFS (risk ratio: 0.85, 95%CI 0.72–0.98), but ORR and CBR were similar to those of anastrozole alone.ConclusionIn the first-line treatment for advanced postmenopausal hormone receptor-positive breast cancer, a combination therapy of CDK4/6 inhibitors and AI showed significant improvement of PFS, ORR, and CBR but with significant increased toxicities compared with AI alone. Fulvestrant 500 mg monotherapy significantly prolonged PFS compared with AI monotherapy. We must wait for the results of the studies with longer follow-up period. ]]> <![CDATA[The African Region early experience with structures for the verification of measles elimination – a review]]> https://www.researchpad.co/article/N20b710fb-b6af-42dc-b50d-f8126f612b7a Substantial progress has been achieved in the last two decades with the implementation of measles control strategies in the African Region. Elimination of measles is defined as the absence of endemic transmission in a defined geographical region or country for at least 12 months, as documented by a well-performing surveillance system. The framework for documenting elimination outlines five lines of evidence that should be utilized in documenting and assessing progress towards measles elimination. In March 2017, the WHO regional office for Africa developed and disseminated regional guidelines for the verification of measles elimination. As of May 2019, fourteen countries in the African Region have established national verification committees and 8 of these have begun to document progress toward measles elimination. Inadequate awareness, concerns about multiple technical committees for immunization work, inadequate funding and human resources, as well as gaps in data quality and in the implementation of measles elimination strategies have been challenges that hindered the establishment and documentation of progress by national verification committees. We recommend continuous capacity building and advocacy, technical assistance and networking to improve the work around the documentation of country progress towards measles elimination in the African Region.

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<![CDATA[Gene drive for population genetic control: non-functional resistance and parental effects]]> https://www.researchpad.co/article/N7498ff75-c52a-4894-ae77-5365b6eb19b4

Gene drive is a natural process of biased inheritance that, in principle, could be used to control pest and vector populations. As with any form of pest control, attention should be paid to the possibility of resistance evolving. For nuclease-based gene drive aimed at suppressing a population, resistance could arise by changes in the target sequence that maintain function, and various strategies have been proposed to reduce the likelihood that such alleles arise. Even if these strategies are successful, it is almost inevitable that alleles will arise at the target site that are resistant to the drive but do not restore function, and the impact of such sequences on the dynamics of control has been little studied. We use population genetic modelling of a strategy targeting a female fertility gene to demonstrate that such alleles may be expected to accumulate, and thereby reduce the reproductive load on the population, if nuclease expression per se causes substantial heterozygote fitness effects or if parental (especially paternal) deposition of nuclease either reduces offspring fitness or affects the genotype of their germline. All these phenomena have been observed in synthetic drive constructs. It will, therefore, be important to allow for non-functional resistance alleles in predicting the dynamics of constructs in cage populations and the impacts of any field release.

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<![CDATA[UV radiation recruits CD4+GATA3+ and CD8+GATA3+ T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo ]]> https://www.researchpad.co/article/Nf920785c-d0a3-455d-9cf5-1f057549dab4

Abstract

Objectives

Solar ultraviolet radiation (UVR) has major adverse effects on human health. While the mechanisms responsible for induction of UVR‐induced inflammation are well‐documented, the mediation of its resolution and longer‐term adaptive homeostasis is unknown. Therefore, we examined the skin immune and lipid profile over time following UVR inflammation.

Methods

To investigate the self‐resolving events of UVR inflammation in vivo, human skin was exposed to a single pro‐inflammatory dose of UVR. Skin biopsies and suction blister fluid were taken at intervals up to 2 weeks post‐UVR. The immune infiltrate was quantified by immunohistochemistry, and lipid mediators were profiled by liquid chromatography/mass spectrometry.

Results

We identified that cellular resolution events including switching of macrophage phenotype apply to human sunburn. However, UVR‐induced inflammation in humans involves a post‐resolution phase that differs from other experimental models. We demonstrate that 2 weeks after the initiating UVR stimulus, there is considerable immune activity with CD8+GATA3+ T cells maintained in human skin. Our results challenge the dogma of CD4+FOXP3+ T cells being the main effector CD4+ T‐cell population following UVR, with CD4+GATA3+ T cells the dominant phenotype. Furthermore, lipid mediators are elevated 14 days post‐UVR, demonstrating the skin lipid microenvironment does not revert to the tissue setting occurring prior to UVR exposure.

Conclusion

We have identified for the first time that CD4+GATA3+ and CD8+GATA3+ T‐cell subpopulations are recruited to UVR‐inflamed human skin, demonstrating discrepancies between the adaptive UVR response in mice and humans. Future strategies to abrogate UVR effects may target these T‐cell subpopulations and also the persistent alteration of the lipid microenvironment post‐UVR.

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<![CDATA[Mucins and their receptors in chronic lung disease]]> https://www.researchpad.co/article/Ne5d98293-d7f4-4236-86d5-48d03bda2b1f

Abstract

There is growing recognition that mucus and mucin biology have a considerable impact on respiratory health, and subsequent global morbidity and mortality. Mucins play a critical role in chronic lung disease, not only by providing a physical barrier and clearing pathogens, but also in immune homeostasis. The aim of this review is to familiarise the reader with the role of mucins in both lung health and disease, with particular focus on function in immunity, infection and inflammation. We will also discuss their receptors, termed glycan‐binding proteins, and how they provide an attractive prospect for therapeutic intervention.

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<![CDATA[Primate thanatology and hominoid mortuary archeology]]> https://www.researchpad.co/article/N8ff7f3d2-a335-42e1-b6ba-ada109405595

In recent years, a thanatology of primates has become a respectable research topic, and although still sparse, observations among several taxa have shown how complex responses to the dead can be. In human evolutionary archeology, re-analysis of old ‘burial’ sites is slowly revising our view on the development of specifically human responses to the dead. We propose here the means of integrating information from the two disciplines of primatology and archeology, in support of the field of primate thanatology. We propose a terminology and a shared set of research questions, from which we generate a number of observations that can be utilized in the field, in order to establish a working dialogue and foster greater collaboration across the two disciplines.

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<![CDATA[Do chimpanzees (Pan troglodytes) console a bereaved mother?]]> https://www.researchpad.co/article/N3be0b15c-ef32-43ff-aa98-b65a6d8c226e

Comparative thanatology encompasses the study of death-related responses in non-human animals and aspires to elucidate the evolutionary origins of human behavior in the context of death. Many reports have revealed that humans are not the only species affected by the death of group members. Non-human primates in particular show behaviors such as congregating around the deceased, carrying the corpse for prolonged periods of time (predominantly mothers carrying dead infants), and inspecting the corpse for signs of life. Here, we extend the focus on death-related responses in non-human animals by exploring whether chimpanzees are inclined to console the bereaved: the individual(s) most closely associated with the deceased. We report a case in which a chimpanzee (Pan troglodytes) mother experienced the loss of her fully developed infant (presumed stillborn). Using observational data to compare the group members’ behavior before and after the death, we found that a substantial number of group members selectively increased their affiliative expressions toward the bereaved mother. Moreover, on the day of the death, we observed heightened expressions of species-typical reassurance behaviors toward the bereaved mother. After ruling out several alternative explanations, we propose that many of the chimpanzees consoled the bereaved mother by means of affiliative and selective empathetic expressions.

Electronic supplementary material

The online version of this article (10.1007/s10329-019-00752-x) contains supplementary material, which is available to authorized users.

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<![CDATA[Intra-community infanticide in wild, eastern chimpanzees: a 24-year review]]> https://www.researchpad.co/article/N79b3d60e-5d7e-48ad-be49-820749fb6055

Infanticide is well documented in chimpanzees and various hypotheses have been proposed to explain this behavior. However, since infanticide by chimpanzees is relatively rare, it has thus far not been possible to thoroughly test these hypotheses. Here we present an analysis of the largest dataset of infanticides from a single community of chimpanzees, a full record of all intra-community infanticides and failed attempts at infanticide over a 24-year period for the Sonso community of chimpanzees in the Budongo Forest, Uganda. We use these data to test four hypotheses for this behavior: the sexual selection hypothesis, male mating competition, resource competition, and meat acquisition. Our dataset consisted of 33 attacks on 30 victims, 11 of which were ‘definite’ infanticides, four of which ‘almost certain’, and nine were ‘suspected’, while nine were ‘attempted’ infanticides. The majority of attacks where the perpetrators were known (23) had only male attackers and victims were disproportionately young (two-thirds of victims with known ages were under 1 week old). Our data best support the sexual selection hypothesis for infanticide. Cannibalism was infrequent and partial, suggesting meat acquisition was a by-product of infanticide, and there was no evidence to suggest that infanticide was part of a male strategy to eliminate future competitors. Infanticide by females was rare, but we suggest sexual selection, operating through intra-sexual competition, may also be responsible for infanticide by females.

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<![CDATA[The clock is ticking: the impact of ageing on T cell metabolism]]> https://www.researchpad.co/article/Ncbb0e73b-73c3-456e-b1a3-3bede6f50ecd

Abstract

It is now clear that access to specific metabolic programmes controls the survival and function of various immune cell populations, including T cells. Efficient naïve and memory T cell homoeostasis requires the use of specific metabolic pathways and differentiation requires rapid and dramatic metabolic remodelling. While we are beginning to appreciate the crucial role of metabolic programming during normal T cell physiology, many of the potential impacts of ageing on metabolic homoeostasis and remodelling in T cells remain unexplored. This review will outline our current understanding of T cell metabolism and explore age‐related metabolic changes that are postulated or have been demonstrated to impact T cell function.

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<![CDATA[Insights into GABAAergic system alteration in Huntington's disease]]> https://www.researchpad.co/article/5c4b8efdd5eed0c48486f3d8

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disease that is characterized by a triad of motor, psychiatric and cognitive impairments. There is still no effective therapy to delay or halt the disease progress. The striatum and cortex are two particularly affected brain regions that exhibit dense reciprocal excitatory glutamate and inhibitory gamma-amino butyric acid (GABA) connections. Imbalance between excitatory and inhibitory signalling is known to greatly affect motor and cognitive processes. Emerging evidence supports the hypothesis that disrupted GABAergic circuits underlie HD pathogenesis. In the present review, we focused on the multiple defects recently found in the GABAergic inhibitory system, including altered GABA level and synthesis, abnormal subunit composition and distribution of GABAA receptors and aberrant GABAA receptor-mediated signalling. In particular, the important role of cation–chloride cotransporters (i.e. NKCC1 and KCC2) is discussed. Recent studies also suggest that neuroinflammation contributes significantly to the abnormal GABAergic inhibition in HD. Thus, GABAA receptors and cation–chloride cotransporters are potential therapeutic targets for HD. Given the limited availability of therapeutic treatments for HD, a better understanding of GABAergic dysfunction in HD could provide novel therapeutic opportunities.

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<![CDATA[Development of clinical simultaneous SPECT/MRI]]> https://www.researchpad.co/article/5c354a03d5eed0c484dbab62

There is increasing clinical use of combined positron emission tomography and MRI, but to date there has been no clinical system developed capable of simultaneous single-photon emission computed tomography (SPECT) and MRI. There has been development of preclinical systems, but there are several challenges faced by researchers who are developing a clinical prototype including the need for the system to be compact and stationary with MRI-compatible components. The limited work in this area is described with specific reference to the Integrated SPECT/MRI for Enhanced stratification in Radio-chemo Therapy (INSERT) project, which is at an advanced stage of developing a clinical prototype. Issues of SPECT/MRI compatibility are outlined and the clinical appeal of such a system is discussed, especially in the management of brain tumour treatment.

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<![CDATA[Framing natural assets for advancing sustainability research: translating different perspectives into actions]]> https://www.researchpad.co/article/5c19b55ad5eed0c484c5c672

Sustainability is a key challenge for humanity in the context of complex and unprecedented global changes. Future Earth, an international research initiative aiming to advance global sustainability science, has recently launched knowledge–action networks (KANs) as mechanisms for delivering its research strategy. The research initiative is currently developing a KAN on “natural assets” to facilitate and enable action-oriented research and synthesis towards natural assets sustainability. ‘Natural assets’ has been adopted by Future Earth as an umbrella term aiming to translate and bridge across different knowledge systems and different perspectives on peoples’ relationships with nature. In this paper, we clarify the framing of Future Earth around natural assets emphasizing the recognition on pluralism and identifying the challenges of translating different visions about the role of natural assets, including via policy formulation, for local to global sustainability challenges. This understanding will be useful to develop inter-and transdisciplinary solutions for human–environmental problems by (i) embracing richer collaborative decision processes and building bridges across different perspectives; (ii) giving emphasis on the interactions between biophysical and socioeconomic drivers affecting the future trends of investments and disinvestments in natural assets; and (iii) focusing on social equity, power relationships for effective application of the natural assets approach. This understanding also intends to inform the scope of the natural asset KAN’s research agenda to mobilize the translation of research into co-designed action for sustainability.

Electronic supplementary material

The online version of this article (10.1007/s11625-018-0599-5) contains supplementary material, which is available to authorized users.

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<![CDATA[Sustainable food systems—a health perspective]]> https://www.researchpad.co/article/5c19b55cd5eed0c484c5c724

Malnutrition in all forms, ranging from undernourishment to obesity and associated diet-related diseases, is one of the leading causes of death worldwide, while food systems often have major environmental impacts. Rapid global population growth and increases in demands for food and changes in dietary habits create challenges to provide universal access to healthy food without creating negative environmental, economic, and social impacts. This article discusses opportunities for and challenges to sustainable food systems from a human health perspective by making the case for avoiding the transition to unhealthy less sustainable diets (using India as an exemplar), reducing food waste by changing consumer behaviour (with examples from Japan), and using innovations and new technologies to reduce the environmental impact of healthy food production. The article touches upon two of the challenges to achieving healthy sustainable diets for a global population, i.e., reduction on the yield and nutritional quality of crops (in particular vegetables and fruits) due to climate change; and trade-offs between food production and industrial crops. There is an urgent need to develop and implement policies and practices that provide universal access to healthy food choices for a growing world population, whilst reducing the environmental footprint of the global food system.

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<![CDATA[Local responses to global sustainability agendas: learning from experimenting with the urban sustainable development goal in Cape Town]]> https://www.researchpad.co/article/5c0c63c0d5eed0c48490dd80

The success of the Sustainable Development Goal 11 (SDG 11) depends on the availability and accessibility of robust data, as well as the reconfiguration of governance systems that can catalyse urban transformation. Given the uneven success of the Millennium Development Goals, and the unprecedented inclusion of the urban in the SDG process, the feasibility of SDG 11 was assessed in advance of its ratification through a series of urban experiments. This paper focusses on Cape Town’s participation in piloting SDG 11, in order to explore the role of urban experimentation in highlighting the partnership arrangements necessary to allow cities to meet the data and governance challenges presented by the SDG 11. Specifically, we focus on the relationship between data and governance that lie at the heart of the SDG 11. The urban experiment demonstrates the highly complex and multi-level governance dynamics that shape the way urban experiments are initiated, executed and concluded. The implications of these dependencies illustrate that more attention needs to be paid at the global level to what data are important and how and where the data are generated if SDG 11 is to be met. Overall, this paper makes the case that the success of SDG 11 rests on effecting local level change and enabling real opportunities in cities.

Electronic supplementary material

The online version of this article (doi:10.1007/s11625-017-0500-y) contains supplementary material, which is available to authorized users.

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<![CDATA[Recent novel approaches to limit oxidative stress and inflammation in diabetic complications]]> https://www.researchpad.co/article/5bfe2bf3d5eed0c4848709c1

Abstract

Diabetes is considered a major burden on the healthcare system of Western and non‐Western societies with the disease reaching epidemic proportions globally. Diabetic patients are highly susceptible to developing micro‐ and macrovascular complications, which contribute significantly to morbidity and mortality rates. Over the past decade, a plethora of research has demonstrated that oxidative stress and inflammation are intricately linked and significant drivers of these diabetic complications. Thus, the focus now has been towards specific mechanism‐based strategies that can target both oxidative stress and inflammatory pathways to improve the outcome of disease burden. This review will focus on the mechanisms that drive these diabetic complications and the feasibility of emerging new therapies to combat oxidative stress and inflammation in the diabetic milieu.

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<![CDATA[The role of IL‐22 in the resolution of sterile and nonsterile inflammation]]> https://www.researchpad.co/article/5bfe2bf1d5eed0c484870929

Abstract

In a broad sense, inflammation can be conveniently characterised by two phases: the first phase, which is a pro‐inflammatory, has evolved to clear infection and/or injured tissue; and the second phase concerns regeneration of normal tissue and restitution of normal physiology. Innate immune cell‐derived pro‐inflammatory cytokines and chemokines activate and recruit nonresident immune cells to the site of infection, thereby amplifying the inflammatory responses to clear infection or injury. This phase is followed by a cytokine milieu that promotes tissue regeneration. There is no absolute temporal distinction between these two phases, and cytokines may have dual pleiotropic effects depending on the timing of release, inflammatory microenvironment or concentrations. IL‐22 is a cytokine with reported pro‐ and anti‐inflammatory roles; in this review, we contend that this protein has primarily a function in restitution of normal tissue and physiology.

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<![CDATA[Exploiting biological and physical determinants of radiotherapy toxicity to individualize treatment]]> https://www.researchpad.co/article/5bc7eccf40307c6b52e0a0c9

The recent advances in radiation delivery can improve tumour control probability (TCP) and reduce treatment-related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally, IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day to day. Daily image guidance scans can be used to identify the position of normal tissue structures and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues that limits radiotherapy (RT) dose and therefore tumour control. However, the dose–response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of RT. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be owing to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In patients with prostate cancer receiving curative RT, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses was −2.7 Gy (5%), and a dose reduction was seen in 7 of the 10 cases. If dose escalation was performed to take rectal dose back to the planned level, this should increase the mean TCP (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical RT who might benefit from either dose escalation, suggesting improved tumour cure or reduced toxicity or both.

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<![CDATA[Is this scaling nonlinear?]]> https://www.researchpad.co/article/5b010157463d7e3f2d9b1e25

One of the most celebrated findings in complex systems in the last decade is that different indexes y (e.g. patents) scale nonlinearly with the population x of the cities in which they appear, i.e. yxβ,β≠1. More recently, the generality of this finding has been questioned in studies that used new databases and different definitions of city boundaries. In this paper, we investigate the existence of nonlinear scaling, using a probabilistic framework in which fluctuations are accounted for explicitly. In particular, we show that this allows not only to (i) estimate β and confidence intervals, but also to (ii) quantify the evidence in favour of β≠1 and (iii) test the hypothesis that the observations are compatible with the nonlinear scaling. We employ this framework to compare five different models to 15 different datasets and we find that the answers to points (i)–(iii) crucially depend on the fluctuations contained in the data, on how they are modelled, and on the fact that the city sizes are heavy-tailed distributed.

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