Global patterns of city size distributions and their fundamental drivers

Urban areas and their voracious appetites are increasingly dominating the flows of energy and materials around the globe. Understanding the size distribution and dynamics of urban areas is vital if we are to manage their growth and mitigate their negative impacts on global ecosystems. For over 50 years, city size distributions have been assumed to universally follow a power function, and many theories have been put forth to explain what has become known as Zipf's law (the instance where the exponent of the power function equals unity). Most previous studies, however, only include the largest cities that comprise the tail of the distribution. Here we show that national, regional and continental city size distributions, whether based on census data or inferred from cluster areas of remotely-sensed nighttime lights, are in fact lognormally distributed through the majority of cities and only approach power functions for the largest cities in the distribution tails. To explore generating processes, we use a simple model incorporating only two basic human dynamics, migration and reproduction, that nonetheless generates distributions very similar to those found empirically. Our results suggest that macroscopic patterns of human settlements may be far more constrained by fundamental ecological principles than more fine-scale socioeconomic factors.     

The allometry of host-pathogen interactions

Background

Understanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.

Methods and Principal Findings

We conducted a literature search to find estimates of the time from infection to first symptoms (t_S) and to death (t_D) for five pathogens infecting a variety of bird and mammal hosts. A broad sampling of diseases (1 bacterial, 1 prion, 3 viruses) indicates that pathogenesis is controlled by the scaling of host metabolism. We find that the time for symptoms to appear is a constant fraction of time to death in all but one disease. Our findings also predict that many population-level attributes of disease dynamics are likely to be expressed as dimensionless quantities that are independent of host body size.

Conclusions and Significance

Our results show that much variability in host pathogenesis can be described by simple power functions consistent with the scaling of host metabolic rate. Assessing how disease progression is controlled by geometric relationships will be important for future research. To our knowledge this is the first study to report the allometric scaling of host/pathogen interactions.     

Renal Fanconi syndrome: developmental basis for a new animal model with relevance to human disease

Using succinylacetone (SA), a metabolite of tyrosine excreted in excess by infants and children with hereditary tyrosinemia and the renal Fanconi syndrome (FS), we have investigated developmentally-related membrane transport events leading to emergence of the generalized renal tubular dysfunction seen in human FS. SA was found to impair sugar and amino acid uptake by both newborn renal tubules and 7-day renal brush-border membrane vesicles (BBMV). This impairment by SA was due in part to a slowing of substrate cotransport rate of 22Na+-entry into BBMV. Concentration-dependent uptake studies indicated SA inhibited the newborn high-affinity transport systems for sugars and amino acids. SA also caused an increase in membrane fluidity and a shift in the thermotropic transition temperature. The demonstrated dual nature of SA's effect on membrane fluidity and O2 consumption, together with the relative contribution of each component to SA-induced transport impairment helps to provide a basis for an understanding of the age-related increases in glucosuria, aminoaciduria and natriuria seen in infants with FS.     

Glucocorticoid type II receptors of the spinal cord show lower affinity than hippocampal type II receptors: binding parameters obtained with different experimental protocols

We have used three experimental protocols to determine binding parameters for type I and type II glucocorticoid receptors in the spinal cord and hippocampus (HIPPO) from adrenalectomized rats. In protocol A, 0.5-20 nM [3H]dexamethasone (DEX) was incubated plus or minus a 1000-fold excess of unlabeled DEX, assuming binding to a two-site model. In protocol B, [3H]DEX competed with a single concentration of RU 28362 (500 nM), whereas in protocol C, we used a concentration of RU 28362 which varied in parallel to that of [3H]DEX, such as 500 x. Results of protocols A and C were qualitatively similar, in that: (1) Bmax for type I receptors favored the HIPPO, while the content of type II sites was comparable in the two tissues; (2) Kd was consistently lower for type I than for type II sites in both tissues; and (3) type II receptors from the spinal cord showed lower affinity than their homologous sites from HIPPO. This last result was also obtained when using protocol B. In contrast, protocol B yielded binding data indicating that type II sites were of similar or higher affinity than type I sites. Computer simulation of the binding protocols demonstrated that protocols A and C were the most theoretically reliable for estimating the Kd and Bmax of type I sites, and the predicted error was smaller for protocol C, in comparison with protocol B. We suggest that the noted differences in the Kd of type II receptors between the spinal cord and HIPPO could account for a difference in sensitivity of the two systems in the physiological adrenal hormone range.     

Ankyrin Repeat‐rich Membrane Spanning/Kidins220 protein regulates dendritic branching and spine stability in vivo

The development of nervous system connectivity depends upon the arborization of dendritic fields and the stabilization of dendritic spine synapses. It is well established that neuronal activity and the neurotrophin BDNF modulate these correlated processes. However, the downstream mechanisms by which these extrinsic signals regulate dendritic development and spine stabilization are less well known. Here we report that a substrate of BDNF signaling, the Ankyrin Repeat‐rich Membrane Spanning (ARMS) protein or Kidins220, plays a critical role in the branching of cortical and hippocampal dendrites and in the turnover of cortical spines. In the barrel somatosensory cortex and the dentate gyrus, regions where ARMS/Kidins220 is highly expressed, no difference in the complexity of dendritic arbors was observed in 1‐month‐old adolescent ARMS/Kidins220^+/? mice compared to wild‐type littermates. However, at 3 months of age, young adult ARMS/Kidins220^+/? mice exhibited decreased dendritic complexity. This suggests that ARMS/Kidins220 does not play a significant role in the initial formation of dendrites but, rather, is involved in the refinement or stabilization of the arbors later in development. In addition, at 1 month of age, the rate of spine elimination was higher in ARMS/Kidins220^+/? mice than in wild‐type mice, suggesting that ARMS/Kidins220^+/? levels regulate spine stability. Taken together, these data suggest that ARMS/Kidins220 is important for the growth of dendritic arbors and spine stability during an activity‐ and BDNF‐dependent period of development. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009     

Risk Factors for Helminth,Malaria, and HIV Infection in Pregnancy in Entebbe,Uganda

Background

Infections during pregnancy may have serious consequences for both mother and baby. Assessment of risk factors for infections informs planning of interventions and analysis of the impact of infections on health outcomes.

Objectives

To describe risk factors for helminths, malaria and HIV in pregnant Ugandan women before intervention in a trial of de-worming in pregnancy.

Methods

The trial recruited 2,507 pregnant women between April 2003 and November 2005. Participants were interviewed and blood and stool samples obtained; location of residence at enrolment was mapped. Demographic, socioeconomic, behavioral and other risk factors were modelled using logistic regression.

Results

There was a high prevalence of helminth, malaria and HIV infection, as previously reported. All helminths and malaria parasitemia were more common in younger women, and education was protective against every infection. Place of birth and/or tribe affected all helminths in a pattern consistent with the geographical distribution of helminth infections in Uganda. Four different geohelminths (hookworm, Trichuris, Ascaris and Trichostrongylus) showed a downwards trend in prevalence during the enrolment period. There was a negative association between hookworm and HIV, and between hookworm and low CD4 count among HIV-positive women. Locally, high prevalence of schistosomiasis and HIV occurred in lakeshore communities.

Conclusions

Interventions for helminths, malaria and HIV need to target young women both in and out of school. Antenatal interventions for malaria and HIV infection must continue to be promoted. Women originating from a high risk area for a helminth infection remain at high risk after migration to a lower-risk area, and vice versa, but overall, geohelminths seem to be becoming less common in this population. High risk populations, such as fishing communities, require directed effort against schistosomiasis and HIV infection.     

Geographic and ecologic heterogeneity in elimination thresholds for the major vector-borne helminthic disease,lymphatic filariasis

Background

Large-scale intervention programmes to control or eliminate several infectious diseases are currently underway worldwide. However, a major unresolved question remains: what are reasonable stopping points for these programmes? Recent theoretical work has highlighted how the ecological complexity and heterogeneity inherent in the transmission dynamics of macroparasites can result in elimination thresholds that vary between local communities. Here, we examine the empirical evidence for this hypothesis and its implications for the global elimination of the major macroparasitic disease, lymphatic filariasis, by applying a novel Bayesian computer simulation procedure to fit a dynamic model of the transmission of this parasitic disease to field data from nine villages with different ecological and geographical characteristics. Baseline lymphatic filariasis microfilarial age-prevalence data from three geographically distinct endemic regions, across which the major vector populations implicated in parasite transmission also differed, were used to fit and calibrate the relevant vector-specific filariasis transmission models. Ensembles of parasite elimination thresholds, generated using the Bayesian fitting procedure, were then examined in order to evaluate site-specific heterogeneity in the values of these thresholds and investigate the ecological factors that may underlie such variability

Results

We show that parameters of density-dependent functions relating to immunity, parasite establishment, as well as parasite aggregation, varied significantly between the nine different settings, contributing to locally varying filarial elimination thresholds. Parasite elimination thresholds predicted for the settings in which the mosquito vector is anopheline were, however, found to be higher than those in which the mosquito is culicine, substantiating our previous theoretical findings. The results also indicate that the probability that the parasite will be eliminated following six rounds of Mass Drug Administration with diethylcarbamazine and albendazole decreases markedly but non-linearly as the annual biting rate and parasite reproduction number increases.

Conclusions

This paper shows that specific ecological conditions in a community can lead to significant local differences in population dynamics and, consequently, elimination threshold estimates for lymphatic filariasis. These findings, and the difficulty of measuring the key local parameters (infection aggregation and acquired immunity) governing differences in transmission thresholds between communities, mean that it is necessary for us to rethink the utility of the current anticipatory approaches for achieving the elimination of filariasis both locally and globally.