Co-evolution of density and topology in a simple model of city formation

We study the influence that population density and the road network have on each others' growth and evolution. We use a simple model of formation and evolution of city roads which reproduces the most important empirical features of street networks in cities. Within this framework, we explicitely introduce the topology of the road network and analyze how it evolves and interact with the evolution of population density. We show that accessibility issues -pushing individuals to get closer to high centrality nodes- lead to high density regions and the appearance of densely populated centers. In particular, this model reproduces the empirical fact that the density profile decreases exponentially from a core district. In this simplified model, the size of the core district depends on the relative importance of transportation and rent costs.Comment: 13 pages, 13 figure

Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab

BACKGROUND The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1500 cells per microliter with end-organ involvement and no recognized secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity. METHODS We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti–interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome. Patients were negative for the FIP1L1–PDGFRA fusion gene and required prednisone monotherapy, 20 to 60 mg per day, to maintain a stable clinical status and a blood eosinophil count of less than 1000 per microliter. Patients received either intravenous mepolizumab or placebo while the prednisone dose was tapered. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks. RESULTS The primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90; 95% confidence interval [CI], 1.59 to 5.26; P CONCLUSIONS Our study shows that treatment with mepolizumab, an agent designed to target eosinophils, can result in corticosteroid-sparing for patients negative for FIP1L1– PDGFRA who have the hypereosinophilic syndrome. (ClinicalTrials.gov number, NCT00086658.

Weather-based prediction of Plasmodium falciparum malaria in epidemic-prone regions of Ethiopia I. Patterns of lagged weather effects reflect biological mechanisms

BACKGROUND: Malaria epidemics due to Plasmodium falciparum are reported frequently in the East African highlands with high case fatality rates. There have been formal attempts to predict epidemics by the use of climatic variables that are predictors of transmission potential. However, little consensus has emerged about the relative importance and predictive value of different factors. Understanding the reasons for variation is crucial to determining specific and important indicators for epidemic prediction. The impact of temperature on the duration of a mosquito's life cycle and the sporogonic phase of the parasite could explain the inconsistent findings. METHODS: Daily average number of cases was modeled using a robust Poisson regression with rainfall, minimum temperature and maximum temperatures as explanatory variables in a polynomial distributed lag model in 10 districts of Ethiopia. To improve reliability and generalizability within similar climatic conditions, we grouped the districts into two climatic zones, hot and cold. RESULTS: In cold districts, rainfall was associated with a delayed increase in malaria cases, while the association in the hot districts occurred at relatively shorter lags. In cold districts, minimum temperature was associated with malaria cases with a delayed effect. In hot districts, the effect of minimum temperature was non-significant at most lags, and much of its contribution was relatively immediate. CONCLUSIONS: The interaction between climatic factors and their biological influence on mosquito and parasite life cycle is a key factor in the association between weather and malaria. These factors should be considered in the development of malaria early warning system

Weather-based prediction of Plasmodium falciparum malaria in epidemic-prone regions of Ethiopia II. Weather-based prediction systems perform comparably to early detection systems in identifying times for interventions

BACKGROUND: Timely and accurate information about the onset of malaria epidemics is essential for effective control activities in epidemic-prone regions. Early warning methods that provide earlier alerts (usually by the use of weather variables) may permit control measures to interrupt transmission earlier in the epidemic, perhaps at the expense of some level of accuracy. METHODS: Expected case numbers were modeled using a Poisson regression with lagged weather factors in a 4(th)-degree polynomial distributed lag model. For each week, the numbers of malaria cases were predicted using coefficients obtained using all years except that for which the prediction was being made. The effectiveness of alerts generated by the prediction system was compared against that of alerts based on observed cases. The usefulness of the prediction system was evaluated in cold and hot districts. RESULTS: The system predicts the overall pattern of cases well, yet underestimates the height of the largest peaks. Relative to alerts triggered by observed cases, the alerts triggered by the predicted number of cases performed slightly worse, within 5% of the detection system. The prediction-based alerts were able to prevent 10–25% more cases at a given sensitivity in cold districts than in hot ones. CONCLUSIONS: The prediction of malaria cases using lagged weather performed well in identifying periods of increased malaria cases. Weather-derived predictions identified epidemics with reasonable accuracy and better timeliness than early detection systems; therefore, the prediction of malarial epidemics using weather is a plausible alternative to early detection systems

Microtiming patterns and interactions with musical properties in Samba music

In this study, we focus on the interaction between microtiming patterns and several musical properties: intensity, meter and spectral characteristics. The data-set of 106 musical audio excerpts is processed by means of an auditory model and then divided into several spectral regions and metric levels. The resulting segments are described in terms of their musical properties, over which patterns of peak positions and their intensities are sought. A clustering algorithm is used to systematize the process of pattern detection. The results confirm previously reported anticipations of the third and fourth semiquavers in a beat. We also argue that these patterns of microtiming deviations interact with different profiles of intensities that change according to the metrical structure and spectral characteristics. In particular, we suggest two new findings: (i) a small delay of microtiming positions at the lower end of the spectrum on the first semiquaver of each beat and (ii) systematic forms of accelerando and ritardando at a microtiming level covering two-beat and four-beat phrases. The results demonstrate the importance of multidimensional interactions with timing aspects of music. However, more research is needed in order to find proper representations for rhythm and microtiming aspects in such contexts

Impact of genomic testing and patient-reported outcomes on receipt of adjuvant chemotherapy

Practice guidelines incorporate genomic tumor profiling, using results such as the Oncotype DX Recurrence Score (RS), to refine recurrence risk estimates for the large proportion of breast cancer patients with early-stage, estrogen receptor-positive disease. We sought to understand the impact of receiving genomic recurrence risk estimates on breast cancer patients’ well-being and the impact of these patient-reported outcomes on receipt of adjuvant chemotherapy. Participants were 193 women (mean age 57) newly diagnosed with early-stage breast cancer. Women were interviewed before and 2–3 weeks after receiving the RS result between 2011 and 2015. We assessed subsequent receipt of chemotherapy from chart review. After receiving their RS, perceived pros (t = 4.27, P < .001) and cons (t = 8.54, P <.001) of chemotherapy increased from pre-test to post-test, while perceived risk of breast cancer recurrence decreased (t = 2.90, P = .004). Women with high RS tumors were more likely to receive chemotherapy than women with low RS tumors (88 vs. 5 %, OR 0.01, 0.00–0.02, P < .001). Higher distress (OR 2.19, 95 % CI 1.05–4.57, P < .05) and lower perceived cons of chemotherapy (OR 0.50, 95 % CI 0.26–0.97, P < .05) also predicted receipt of chemotherapy. Distressed patients who saw few downsides of chemotherapy received this treatment. Clinicians should consider these factors when discussing chemotherapy with breast cancer patients

Dynamic assembly of ribbon synapses and circuit maintenance in a vertebrate sensory system

Ribbon synapses transmit information in sensory systems, but their development is not well understood. To test the hypothesis that ribbon assembly stabilizes nascent synapses, we performed simultaneous time-lapse imaging of fluorescently-tagged ribbons in retinal cone bipolar cells (BCs) and postsynaptic densities (PSD95-FP) of retinal ganglion cells (RGCs). Ribbons and PSD95-FP clusters were more stable when these components colocalized at synapses. However, synapse density on ON-alpha RGCs was unchanged in mice lacking ribbons (ribeye knockout). Wildtype BCs make both ribbon-containing and ribbon-free synapses with these GCs even at maturity. Ribbon assembly and cone BC-RGC synapse maintenance are thus regulated independently. Despite the absence of synaptic ribbons, RGCs continued to respond robustly to light stimuli, although quantitative examination of the responses revealed reduced frequency and contrast sensitivity