Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in Sao Paulo, Brazil

The dengue virus has a single-stranded positive-sense RNA genome of similar to 10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1-4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in Sao Jose do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000-2001. Sixty DENV-3 from Sao Jose do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R(0) = 1.53 and values for lineage 2 of R(0) = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area.

Influences of sex and age on biological rhythms of serum lipids and lipoproteins

Background: Few studies have evaluated seasonal variations of biochemical parameters routinely analyzed in clinical laboratories. Rhythmic patterns for lipids and lipoproteins have been demonstrated and have been the object of research, mainly because of their demonstrated association with coronary artery disease. This study evaluated the occurrence of biological rhythms on serum lipids and lipoproteins and the effects of sex and age on the rhythms in a Brazilian hospital outpatient population. Methods: Retrospective laboratory study was carried out to evaluate the results of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides (TG), from individuals registered at a university referral hospital over 8years. The studied population was composed of individuals of both sexes and all ages totaling 38,579 participants and 301,934 measurements. Statistical analyses were carried out using the SAS program and the temporal analysis used the Cosinor method. Results: TG rhythm was present only in females. All other parameters were equally rhythmic in both sexes. Regarding age, HDL-C presented rhythms in all age groups, but TC and LDL-C showed seasonality only for those > 13years, TG did not present rhythms in all age groups. Conclusion: Effects of sex and age on biological rhythms detected in TC, LDL-C and HDL-C should be considered a significant cause of pre-analytical variation in these laboratory tests. (C) 2009 Elsevier B.V. All rights reserved.

AIDS along Brazil`s borders, 1990-2003

Objective. To study the AIDS epidemic in Brazil`s border areas, from the spatial and temporal perspective. Methods. This was an ecological study in which the cases of AIDS reported to the Ministry of Health of Brazil from 1990-2003 were grouped according to ""hunger areas"" as defined by Josue de Castro in the 1940s and according to 19 cultural subregions. Spatial assessment was based on incidence rates for border municipalities; temporal assessment considered the absolute number of cases occurring quarterly from 1990-2003 in each of the hunger areas studied (Extreme South, Midwest, and Amazon). Results. During the study period, 7 973 cases of AIDS were reported from the Brazilian border areas: 648 in the Amazon area, 1 579 in the Midwest, and 5 746 in the Extreme South (populations of 668 098, 895 489, and 2 769 361, respectively). The subregions with the highest AIDS incidence rates in each of the three border areas were those near triple-borders, between more than two Latin American countries. Sexual transmission was predominant, with heterosexual transmission being the most frequent, followed by transmission by male homosexuality. These two categories accounted for 87.2% of the cases reported. The estimates of the trend parameter in the temporal analysis were 0.53 (P < 0.0001), 0.83 (P < 0.0001), and 3.47 (P < 0.0001), respectively, for the Amazon, Midwest, and Extreme South areas. Conclusion. The improvement of health care services along Brazil`s borders may be a strategy for territorial integration and for dealing with the AIDS epidemic, as long as social, economic, and cultural differences are taken into account.

Induced seismicity in the Castarthao reservoir, NE Brazil - Preliminary results

The Castanhao reservoir was built in the state of Ceara, a dry region in Northeastern Brazil, to regulate the flow of the Jaguaribe River, for irrigation, and for power generation. It is an earth-filled dam, 60 m high, with a water capacity of 4.5 x 10(9) m(3). The seismicity in the area has been monitored since 1998, with a few interruptions, using one analog or one digital station and, during a few periods, a three-station network. The first earthquakes likely to be induced events were detected in 2003, when the water level was about 20 in high. In early 2004 a very heavy rainfall season quickly filled the reservoir. Shortly after, an increase in the seismic activity occurred and many micro-earthquakes were recorded. We suggest that this activity resulted from an increase in pore pressure due to undrained response. Therefore, we may classify this cluster of microearthquakes as ""initial seismicity."" We deployed a network with four analog stations in the area, following this activity, to determine the epicentral zone. At least three epicentral areas under the reservoir were detected. The spatio-temporal analysis of the available data revealed that the seismicity occurs in clusters and that these were activated at different periods. We identified four sets of faults (N-S-, E-W-, NW-SE-, and NE-SW-oriented), some of which moved in shallow crustal levels and as recently as the Quaternary (1.8 Ma). Under the present-day stress regime, the last two sets moved as strike-slip structures. We suggest a possible correlation between dormant faults and the observed induced seismicity. (c) 2008 Elsevier B.V. All rights reserved.

A psychophysical and computational analysis of the spatio-temporal mechanisms underlying the flash-lag effect

Several accounts put forth to explain the flash-lag effect (FLE) rely mainly on either spatial or temporal mechanisms. Here we investigated the relationship between these mechanisms by psychophysical and theoretical approaches. In a first experiment we assessed the magnitudes of the FLE and temporal-order judgments performed under identical visual stimulation. The results were interpreted by means of simulations of an artificial neural network, that wits also employed to make predictions concerning the F LE. The model predicted that a spatio-temporal mislocalisation would emerge from two, continuous and abrupt-onset, moving stimuli. Additionally, a straightforward prediction of the model revealed that the magnitude of this mislocalisation should be task-dependent, increasing when the use of the abrupt-onset moving stimulus switches from a temporal marker only to both temporal and spatial markers. Our findings confirmed the model`s predictions and point to an indissoluble interplay between spatial facilitation and processing delays in the FLE.

Temporal variation of the phytoplankton community at short sampling intervals in the Mundaú reservoir, Northeastern Brazil

The aim of this study was to determine how abiotic factors drive the phytoplankton community in a water supply reservoir within short sampling intervals. Samples were collected at the subsurface (0.1 m) and bottom of limnetic (8 m) and littoral (2 m) zones in both the dry and rainy seasons. The following abiotic variables were analyzed: water temperature, dissolved oxygen, electrical conductivity, total dissolved solids, turbidity, pH, total nitrogen, nitrite, nitrate, total phosphorus, total dissolved phosphorus and orthophosphate. Phytoplankton biomass was determined from biovolume values. The role abiotic variables play in the dynamics of phytoplankton species was determined by means of Canonical Correspondence Analysis. Algae biomass ranged from 1.17×10(4) to 9.21×10(4) µg.L-1; cyanobacteria had biomass values ranging from 1.07×10(4) to 8.21×10(4) µg.L-1. High availability of phosphorous, nitrogen limitation, alkaline pH and thermal stability all favored cyanobacteria blooms, particularly during the dry season. Temperature, pH, total phosphorous and turbidity were key factors in characterizing the phytoplankton community between sampling times and stations. Of the species studied, Cylindrospermopsis raciborskii populations were dominant in the phytoplankton in both the dry and rainy seasons. We conclude that the phytoplankton was strongly influenced by abiotic variables, particularly in relation to seasonal distribution patterns.

Spatial and temporal distribution of fish in Palmas bay, Ubatuba, Brazil

The aim of this study was to analyze the distribution and abundance of the fish fauna of Palmas bay on Anchieta Island in southeastern Brazil. Specimens were caught in the summer and winter of 1992, using an otter trawl at three locations in the bay. The specimens were caught in both the nighttime and daytime. Data on the water temperature and salinity were recorded for the characterization of the predominant water mass in the region, and sediment samples were taken for granulometric analysis. A total of 7 656 specimens (79 species), with a total weight of approximately 300 kg, were recorded. The most abundant species were Eucinostomus argenteus, Ctenosciaena gracilicirrhus, Haemulon steindachneri, Eucinostomus gula and Diapterus rhombeus, which together accounted for more than 73% of the sample. In general, the ecological indices showed no differences in the composition of species for the abiotic variables analyzed. The multivariate analysis showed that the variations in the distribution of the fish fauna were mainly associated with intra-annual differences in temperature and salinity, resulting from the presence of South Atlantic Central Water (SACW) in the area during the summer. The analysis also showed an association with the type of bottom and a lesser association with respect to the night/day periods.

Analysis of mangrove forest succession, using sediment cores: a case study in the Cananéia -Iguape coastal system, São Paulo Brazil

Sediment cores are an essential tool for the analysis of the dynamics of mangrove succession. Coring was used to correlate changes in depositional environments and lateral sedimentary facies with discrete stages of forest succession at the Cananéia-Iguape Coastal System in southeastern Brazil. A local level successional pattern was examined based on four core series T1) a sediment bank; T2) a smooth cordgrass Spartina alterniflora bank; T3) an active mangrove progradation fringe dominated by Laguncularia racemosa, and; T4) a mature mangrove forest dominated by Avicennia schaueriana. Cores were macroscopically described in terms of color, texture, sedimentary structure and organic components. The base of all cores exhibited a similar pattern suggesting common vertical progressive changes in depositional conditions and subsequent successional colonization pattern throughout the forest. The progradation zone is an exposed bank, colonized by S. alterniflora. L. racemosa, replaces S. alterniflora as progradation takes place. As the substrate consolidates A. schaueriana replaces L. racemosa and attains the greatest structural development in the mature forest. Cores collected within the A. schaueriana dominated stand contained S. alterniflora fragments near the base, confirming that a smooth cordgrass habitat characterized the establishment and early seral stages. Cores provide a reliable approach to describe local-level successional sequences in dynamic settings subject to drivers operating on multiple temporal and spatial scales where spatial heterogeneity can lead to multiple equilibria and where similar successional end-points may be reached through convergent paths.

A descriptive analysis of the seasonal variation of physical oceanographic characteristics in the northern region of the Todos os Santos Bay (Bahia, Brazil)

The results obtained in the August and December 2003, August 2004 and January 2005 oceanographic campaigns in the northern region of the Todos os Santos Bay (lat. 12º44.5'S; long. 038º35.00'W) between the Madre de Deus and Maré islands are analyzed. Instruments of continuous and discrete samplings were used to measure hydrographic properties currents and tides. The water mass of the northern region of the bay is forced by semidiurnal and mesotides of form number 0.08 and the lunar component M2 height was estimated at 91cm. The time series of the surface currents indicated movements in the N/S direction, forced by the tide with maximum magnitudes of 0.73 m.s-1 on the December 2003 campaign. However, in August 2004 the currents were dominated by the wind stress forcing, with a maximum speed of 1.85 m.s-1 and SE direction. Near the bottom, the influence of the tide is not as evident, with a decrease in intensity due to internal and bottom friction, with a maximum velocity of 0.17 m.s-1. The thermal and haline structures were weakly horizontally, as well as vertically stratified, with extreme values varying in the intervals 23ºC (August, 2004) to 28ºC (December, 2003) and 31.0 psu (August, 2003) to 36.0 psu (December, 2003), respectively. Some conclusions may be drawn from these results: i) The signs of the dilution of the fresh water discharges of the Caípe, Mataripe and São Paulo rivers in the region under the influence of the RLAM were observed only during the winter periods, but in the summer the region was flooded by waters of oceanic origin and the salinities above 36.0 indicated TW mass intrusion; ii) The N-S circulation near the RLAM is strongly dominated by the tide, and the importance of the M2 component was unequivocal, however, the E-W component presented some tidal modulation away from abrupt bottom topographical changes, and iii) The residual series, calculated as the difference between the original and modeled, is about ¼ of the original and confirmed its semidiurnal character.

Tendência temporal e desigualdades na mortalidade por diarreias em menores de 5 anos

OBJETIVO: Analisar a tendência da mortalidade por diarreia entre menores de 5 anos, no município de Osasco (SP), entre 1980 e 2000. MÉTODOS: Trata-se de estudo observacional com dois delineamentos. Um descritivo, que toma o indivíduo como unidade do estudo, e outro ecológico, analisando agregado populacional que incluiu análise de séries temporais. A fonte de dados foi o sistema de informação de mortalidade do Estado de São Paulo e censos de 1980, 1991 e 2000. Descreveu-se a variação sazonal e para a análise de tendência aplicaram-se modelos log lineares de regressão polinomiais, utilizando-se variáveis sociodemográficas da criança e da mãe. Foram analisadas a evolução de indicadores sociodemográficos do município de 1980 a 2000, as taxas médias de mortalidade por diarreia nos menores de 5 anos e seus diferenciais por distrito nos anos 90. RESULTADOS: Dos 1.360 óbitos, 94,3 e 75,3% atingiram, respectivamente, menores de 1 ano e de 6 meses. O declínio da mortalidade foi de 98,3%, com deslocamento da sazonalidade do verão para o outono. A mediana da idade elevou-se de 2 meses nos primeiros períodos para 3 meses no último. O resíduo de óbitos manteve-se entre filhos de mães de 20 a 29 anos e escolaridade < 8 anos. O risco relativo entre o distrito mais atingido e a taxa média do município diminuiu de 3,4 para 1,3 do primeiro para o segundo quinquênio dos anos 90. CONCLUSÃO: Nossos resultados apontam uma elevação da idade mais vulnerável e a provável mudança do agente mais frequentemente associado ao óbito por diarreia.

Tendência temporal e desigualdades na mortalidade por diarreias em

Objetivo: Analisar a tendência da mortalidade por diarreia entre menores de 5 anos, no município de Osasco (SP), entre 1980 e 2000. Métodos: Trata-se de estudo observacional com dois delineamentos. Um descritivo, que toma o indivíduo como unidade do estudo, e outro ecológico, analisando agregado populacional que incluiu análise de séries temporais. A fonte de dados foi o sistema de informação de mortalidade do Estado de São Paulo e censos de 1980, 1991 e 2000. Descreveu-se a variação sazonal e para a análise de tendência aplicaram-se modelos log lineares de regressão polinomiais, utilizando-se variáveis sociodemográficas da criança e da mãe. Foram analisadas a evolução de indicadores sociodemográficos do município de 1980 a 2000, as taxas médias de mortalidade por diarreia nos menores de 5 anos e seus diferenciais por distrito nos anos 90. Resultados: Dos 1.360 óbitos, 94,3 e 75,3% atingiram, respectivamente, menores de 1 ano e de 6 meses. O declínio da mortalidade foi de 98,3%, com deslocamento da sazonalidade do verão para o outono. A mediana da idade elevou-se de 2 meses nos primeiros períodos para 3 meses no último. O resíduo de óbitos manteve-se entre filhos de mães de 20 a 29 anos e escolaridade < 8 anos. O risco relativo entre o distrito mais atingido e a taxa média do município diminuiu de 3,4 para 1,3 do primeiro para o segundo quinquênio dos anos 90. Conclusão: Nossos resultados apontam uma elevação da idade mais vulnerável e a provável mudança do agente mais frequentemente associado ao óbito por diarreia

Gait kinematic analysis in patients with a mild form of central cord syndrome

Background: Central cord syndrome (CCS) is considered the most common incomplete spinal cord injury (SCI). Independent ambulation was achieved in 87-97% in young patients with CCS but no gait analysis studies have been reported before in such pathology. The aim of this study was to analyze the gait characteristics of subjects with CCS and to compare the findings with a healthy age, sex and anthropomorphically matched control group (CG), walking both at a self-selected speed and at the same speed. Methods: Twelve CCS patients and a CG of twenty subjects were analyzed. Kinematic data were obtained using a three-dimensional motion analysis system with two scanner units. The CG were asked to walk at two different speeds, at a self-selected speed and at a slower one, similar to the mean gait speed previously registered in the CCS patient group. Temporal, spatial variables and kinematic variables (maximum and minimum lower limb joint angles throughout the gait cycle in each plane, along with the gait cycle instants of occurrence and the joint range of motion ROM) were compared between the two groups walking at similar speeds. Results: The kinematic parameters were compared when both groups walked at a similar speed, given that there was a significant difference in the self-selected speeds (p < 0.05). Hip abduction and knee flexion at initial contact, as well as minimal knee flexion at stance, were larger in the CCS group (p < 0.05). However, the range of knee and ankle motion in the sagittal plane was greater in the CG group (p < 0.05). The maximal ankle plantar-flexion values in stance phase and at toe off were larger in the CG (p < 0.05). Conclusions: The gait pattern of CCS patients showed a decrease of knee and ankle sagittal ROM during level walking and an increase in hip abduction to increase base of support. The findings of this study help to improve the understanding how CCS affects gait changes in the lower limbs.

Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

Background: Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing. Methods: We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area - BA22p) identifying by mass spectrometry several protein expression alterations that could be related to the disease. Results: Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6) and glial fibrillary acidic protein (GFAP) were confirmed by western blot in schizophrenia prefrontal cortex. Conclusion: Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.

A Dynamic Analysis of Tuberculosis Dissemination to Improve Control and Surveillance

Background: Detailed analysis of the dynamic interactions among biological, environmental, social, and economic factors that favour the spread of certain diseases is extremely useful for designing effective control strategies. Diseases like tuberculosis that kills somebody every 15 seconds in the world, require methods that take into account the disease dynamics to design truly efficient control and surveillance strategies. The usual and well established statistical approaches provide insights into the cause-effect relationships that favour disease transmission but they only estimate risk areas, spatial or temporal trends. Here we introduce a novel approach that allows figuring out the dynamical behaviour of the disease spreading. This information can subsequently be used to validate mathematical models of the dissemination process from which the underlying mechanisms that are responsible for this spreading could be inferred. Methodology/Principal Findings: The method presented here is based on the analysis of the spread of tuberculosis in a Brazilian endemic city during five consecutive years. The detailed analysis of the spatio-temporal correlation of the yearly geo-referenced data, using different characteristic times of the disease evolution, allowed us to trace the temporal path of the aetiological agent, to locate the sources of infection, and to characterize the dynamics of disease spreading. Consequently, the method also allowed for the identification of socio-economic factors that influence the process. Conclusions/Significance: The information obtained can contribute to more effective budget allocation, drug distribution and recruitment of human skilled resources, as well as guiding the design of vaccination programs. We propose that this novel strategy can also be applied to the evaluation of other diseases as well as other social processes.

Gene Expression Complex Networks: Synthesis, Identification, and Analysis

Thanks to recent advances in molecular biology, allied to an ever increasing amount of experimental data, the functional state of thousands of genes can now be extracted simultaneously by using methods such as cDNA microarrays and RNA-Seq. Particularly important related investigations are the modeling and identification of gene regulatory networks from expression data sets. Such a knowledge is fundamental for many applications, such as disease treatment, therapeutic intervention strategies and drugs design, as well as for planning high-throughput new experiments. Methods have been developed for gene networks modeling and identification from expression profiles. However, an important open problem regards how to validate such approaches and its results. This work presents an objective approach for validation of gene network modeling and identification which comprises the following three main aspects: (1) Artificial Gene Networks (AGNs) model generation through theoretical models of complex networks, which is used to simulate temporal expression data; (2) a computational method for gene network identification from the simulated data, which is founded on a feature selection approach where a target gene is fixed and the expression profile is observed for all other genes in order to identify a relevant subset of predictors; and (3) validation of the identified AGN-based network through comparison with the original network. The proposed framework allows several types of AGNs to be generated and used in order to simulate temporal expression data. The results of the network identification method can then be compared to the original network in order to estimate its properties and accuracy. Some of the most important theoretical models of complex networks have been assessed: the uniformly-random Erdos-Renyi (ER), the small-world Watts-Strogatz (WS), the scale-free Barabasi-Albert (BA), and geographical networks (GG). The experimental results indicate that the inference method was sensitive to average degree k variation, decreasing its network recovery rate with the increase of k. The signal size was important for the inference method to get better accuracy in the network identification rate, presenting very good results with small expression profiles. However, the adopted inference method was not sensible to recognize distinct structures of interaction among genes, presenting a similar behavior when applied to different network topologies. In summary, the proposed framework, though simple, was adequate for the validation of the inferred networks by identifying some properties of the evaluated method, which can be extended to other inference methods.