Amazonian malaria: Asymptomatic human reservoirs, diagnostic challenges, environmentally driven changes in mosquito vector populations, and the mandate for sustainable control strategies

Across the Americas and the Caribbean, nearly 561,000 slide-confirmed malaria infections were reported officially in 2008. The nine Amazonian countries accounted for 89% of these infections; Brazil and Peru alone contributed 56% and 7% of them, respectively. Local populations of the relatively neglected parasite Plasmodium vivax, which currently accounts for 77% of the regional malaria burden, are extremely diverse genetically and geographically structured. At a time when malaria elimination is placed on the public health agenda of several endemic countries, it remains unclear why malaria proved so difficult to control in areas of relatively low levels of transmission such as the Amazon Basin. We hypothesize that asymptomatic parasite carriage and massive environmental changes that affect vector abundance and behavior are major contributors to malaria transmission in epidemiologically diverse areas across the Amazon Basin. Here we review available data supporting this hypothesis and discuss their implications for current and future malaria intervention policies in the region. Given that locally generated scientific evidence is urgently required to support malaria control interventions in Amazonia, we briefly describe the aims of our current field-oriented malaria research in rural villages and gold-mining enclaves in Peru and a recently opened agricultural settlement in Brazil. (C) 2011 Elsevier B.V. All rights reserved.

Characterization of the procera Tomato Mutant Shows Novel Functions of the SlDELLA Protein in the Control of Flower Morphology, Cell Division and Expansion, and the Auxin-Signaling Pathway during Fruit-Set and Development

procera (pro) is a tall tomato (Solanum lycopersicum) mutant carrying a point mutation in the GRAS region of the gene encoding SlDELLA, a repressor in the gibberellin (GA) signaling pathway. Consistent with the SlDELLA loss of function, pro plants display a GA-constitutive response phenotype, mimicking wild-type plants treated with GA(3). The ovaries from both nonemasculated and emasculated pro flowers had very strong parthenocarpic capacity, associated with enhanced growth of preanthesis ovaries due to more and larger cells. pro parthenocarpy is facultative because seeded fruits were obtained by manual pollination. Most pro pistils had exserted stigmas, thus preventing self-pollination, similar to wild-type pistils treated with GA(3) or auxins. However, Style2.1, a gene responsible for long styles in noncultivated tomato, may not control the enhanced style elongation of pro pistils, because its expression was not higher in pro styles and did not increase upon GA(3) application. Interestingly, a high percentage of pro flowers had meristic alterations, with one additional petal, sepal, stamen, and carpel at each of the four whorls, respectively, thus unveiling a role of SlDELLA in flower organ development. Microarray analysis showed significant changes in the transcriptome of preanthesis pro ovaries compared with the wild type, indicating that the molecular mechanism underlying the parthenocarpic capacity of pro is complex and that it is mainly associated with changes in the expression of genes involved in GA and auxin pathways. Interestingly, it was found that GA activity modulates the expression of cell division and expansion genes and an auxin signaling gene (tomato AUXIN RESPONSE FACTOR7) during fruit-set.

Suppression of vortex-induced vibration using moving surface boundary-layer control

Experimental results of flow around a circular cylinder with moving surface boundary-layer control (MSBC) are presented. Two small rotating cylinders strategically located inject momentum in the boundary layer of the cylinder, which delays the separation of the boundary layer. As a consequence, the wake becomes narrower and the fluctuating transverse velocity is reduced, resulting in a recirculation free region that prevents the vortex formation. The control parameter is the ratio between the tangential velocity of the moving surface and the flow velocity (U-c/U). The main advantage of the MSBC is the possibility of combining the suppression of vortex-induced vibration (VIV) and drag reduction. The experimental tests are preformed at a circulating water channel facility and the circular cylinders are mounted on a low-damping air bearing base with one degree-of-freedom in the transverse direction of the channel flow. The mass ratio is 1.8. The Reynolds number ranges from 1600 to 7500, the reduced velocity varies up to 17, and the control parameter interval is U-c/U = 5-10. A significant decreasing in the maximum amplitude of oscillation for the cylinder with MSBC is observed. Drag measurements are obtained for statically mounted cylinders with and without MSBC. The use of the flow control results in a mean drag reduction at U-c/U = 5 of almost 60% compared to the plain cylinder. PIV velocity fields of the wake of static cylinders are measured at Re = 3000. The results show that the wake is highly organized and narrower compared to the one observed in cylinders without control. The calculation of the total variance of the fluctuating transverse velocity in the wake region allows the introduction of an active closed-loop control. The experimental results are in good agreement with the numerical simulation studies conducted by other researchers for cylinders with MSBC. (C) 2012 Elsevier Ltd. All rights reserved.

Neuropathology and behavioral impairments after three types of global ischemia surgery in Meriones unguiculatus: Evidence in motor cortex, hippocampal CA1 region and the neostriatum

The effects of three types of global ischemia by occlusion of carotid artery on motor and exploratory behaviors of Gerbils were evaluated by the Activity Cage and Rota rod tests. Animals were divided based on two surgical criteria: unilateral (UNI) or bilateral (BIL) carotid occlusion, with (REP) or without (OCL) reperfusion; and their behavior was evaluated on the fourth (4) or sixth (6) day. There was reduction of cell number in striatum, motor cortex M1 area, and hippocampal CA1 area in all groups in comparison to control animals. For M1 area and striatum, the largest reduction was observed in UNI6, UNI4, and BIL4 groups. Neuronal loss was also observed in CA1 area of BIL4 rodents. There was a decrease in crossings and rearings in all groups in activity cage test, compared to control. Reperfusion, unilateral and bilateral occlusion groups showed decrease in crossings. Only the BIL4 showed a decrease of rearing. In the Rota rod test, except the UNIOCL6, the groups showed a decrease in the balance in comparison to control. Both groups with REP4 showed a major decrease in balance. These findings suggest that both unilateral and bilateral carotid occlusions with reperfusion produce impairments of motor and exploratory behavior. (C) 2011 Elsevier B.V. All rights reserved.

Characterization of Stability Region for General Autonomous Nonlinear Dynamical Systems

The existing characterization of stability regions was developed under the assumption that limit sets on the stability boundary are exclusively composed of hyperbolic equilibrium points and closed orbits. The characterizations derived in this technical note are a generalization of existing results in the theory of stability regions. A characterization of the stability boundary of general autonomous nonlinear dynamical systems is developed under the assumption that limit sets on the stability boundary are composed of a countable number of disjoint and indecomposable components, which can be equilibrium points, closed orbits, quasi-periodic solutions and even chaotic invariant sets.

Limitations of Neoseiulus baraki and Proctolaelaps bickleyi as control agents of Aceria guerreronis

Several predatory mites have been found in association with the coconut mite, Aceria guerreronis Keifer, in northeast Brazil. However, the latter still causes damage to coconut in that region. The objectives of this work were to compare the frequencies of occurrence of Neoseiulus (Phytoseiidae) and Proctolaelaps (Melicharidae) species on standing and aborted coconuts in coastal Pernambuco State, northeast Brazil and to analyze their possible limitations as control agents of the coconut mite, based on evaluations of the restrictions they may have to access the microhabitat inhabited by the pest and their functional and reproductive responses to increasing densities of the latter. Neoseiulus baraki (Athias-Henriot) was found mostly on standing coconuts whereas Proctolaelaps bickleyi (Bram) was found mostly on aborted coconuts. Measurements of the entrance to the microhabitat occupied by the coconut mite, between the bracts and the subjacent fruit surface, showed that this different pattern of predator prevalence could be related to predator sizes, although other environmental factors could not be disregarded. Progressively higher predation rate of N. baraki was observed up to an experimental density that corresponded to 1,200 coconut mites per fruit, which is close to the average number determined in northeast Brazil, reducing slightly afterwards. Predation rate of P. bickleyi reduced consistently but slightly with increasing prey densities, but in absolute values, rates were always much higher than determined for N. baraki. The excessively high killing capacity of P. bickleyi, probably related to its high feeding requirement, may be detrimental in terms of stability. In fact, such high requirement for food suggests that P. bickleyi might not have a strong relation with the coconut mite and that the latter may not be its main food source under natural conditions. It is concluded that body sizes of both predators and the exceedingly high feeding requirement of P. bickleyi may limit their performance as control agents of the coconut mite.

Occupational safety and health practices among flower greenhouses workers from Alto Tiete region (Brazil)

In this preliminary study the occupational safety and health practices among flower greenhouses workers were evaluated. The study was carried out in the alto Tiete region, located at the Sao Paulo State, Brazil. Inadequate welfare facilities; poor pesticide storage, use and disposal conditions; use of highly toxic pesticides; lack of adequate data regarding pesticide use; and incorrect use and maintenance of PPE were observed in most of the visited greenhouses. These results suggest that, in greenhouses, workers may be at higher risk of pesticide exposure, due to many factors that can intensify the exposure such as the lack of control on reentry intervals after pesticide application. Specific regulations are needed to ensure better OSH practices on pesticide use and to improve working conditions in greenhouses, in order to deal with the peculiarities of greenhouse working environment. Some of the special requirements for greenhouses workers' protection are the establishment of ventilation criteria for restricted entry interval; clear reentry restrictions; and EPI for workers other than applicators that need to enter the greenhouse before expiring REI interval. Another important way to improve OSH practices among workers includes the distribution of simple guidelines on the dos and don'ts regarding OSH practices in greenhouses and extensively training interventions to change the perception of hazards and the behavior towards risk. (C) 2011 Elsevier B.V. All rights reserved.

Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats

Uridine adenosine tetraphosphate (Up(4)A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up(4)A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y(2)/P2Y(4) agonist), UDP (P2Y(6) agonist), and alpha,beta-methylene ATP (P2X(1) agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up(4)A-, ATP-, and UP-induced contractions were unchanged; (2) in basilar artery, Up(4)A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X(1), but not P2Y(2) or P2Y(6) was decreased; (3) in small mesenteric artery, Up(4)A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y(2) and P2X(1) was decreased whereas P2Y(6) expression was increased; (4) in femoral artery, Up(4)A-. UTP-, and UDP-induced contractions were increased, but expression of P2Y(2), P2Y(6) and P2X(1) was unchanged. The alpha,beta-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up(4)A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up(4)A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up(4)A may be adaptive to the vascular alterations produced by hypertension. (C) 2011 Elsevier Ltd. All rights reserved.

Cost effectiveness of OptiMal® rapid diagnostic test for malaria in remote areas of the Amazon Region, Brazil

Abstract Background In areas with limited structure in place for microscopy diagnosis, rapid diagnostic tests (RDT) have been demonstrated to be effective. Method The cost-effectiveness of the Optimal® and thick smear microscopy was estimated and compared. Data were collected on remote areas of 12 municipalities in the Brazilian Amazon. Data sources included the National Malaria Control Programme of the Ministry of Health, the National Healthcare System reimbursement table, hospitalization records, primary data collected from the municipalities, and scientific literature. The perspective was that of the Brazilian public health system, the analytical horizon was from the start of fever until the diagnostic results provided to patient and the temporal reference was that of year 2006. The results were expressed in costs per adequately diagnosed cases in 2006 U.S. dollars. Sensitivity analysis was performed considering key model parameters. Results In the case base scenario, considering 92% and 95% sensitivity for thick smear microscopy to Plasmodium falciparum and Plasmodium vivax, respectively, and 100% specificity for both species, thick smear microscopy is more costly and more effective, with an incremental cost estimated at US$549.9 per adequately diagnosed case. In sensitivity analysis, when sensitivity and specificity of microscopy for P. vivax were 0.90 and 0.98, respectively, and when its sensitivity for P. falciparum was 0.83, the RDT was more cost-effective than microscopy. Conclusion Microscopy is more cost-effective than OptiMal® in these remote areas if high accuracy of microscopy is maintained in the field. Decision regarding use of rapid tests for diagnosis of malaria in these areas depends on current microscopy accuracy in the field.

A new approach for modeling and control of nonlinear systems via norm-bounded linear differential inclusions

A systematic approach to model nonlinear systems using norm-bounded linear differential inclusions (NLDIs) is proposed in this paper. The resulting NLDI model is suitable for the application of linear control design techniques and, therefore, it is possible to fulfill certain specifications for the underlying nonlinear system, within an operating region of interest in the state-space, using a linear controller designed for this NLDI model. Hence, a procedure to design a dynamic output feedback controller for the NLDI model is also proposed in this paper. One of the main contributions of the proposed modeling and control approach is the use of the mean-value theorem to represent the nonlinear system by a linear parameter-varying model, which is then mapped into a polytopic linear differential inclusion (PLDI) within the region of interest. To avoid the combinatorial problem that is inherent of polytopic models for medium- and large-sized systems, the PLDI is transformed into an NLDI, and the whole process is carried out ensuring that all trajectories of the underlying nonlinear system are also trajectories of the resulting NLDI within the operating region of interest. Furthermore, it is also possible to choose a particular structure for the NLDI parameters to reduce the conservatism in the representation of the nonlinear system by the NLDI model, and this feature is also one important contribution of this paper. Once the NLDI representation of the nonlinear system is obtained, the paper proposes the application of a linear control design method to this representation. The design is based on quadratic Lyapunov functions and formulated as search problem over a set of bilinear matrix inequalities (BMIs), which is solved using a two-step separation procedure that maps the BMIs into a set of corresponding linear matrix inequalities. Two numerical examples are given to demonstrate the effectiveness of the proposed approach.

Mycobacterium bovis infection in goats from the Northeast Region of Brazil

A total of 8,058 male and female mixed-breed goats and 1-4 years of age were slaughtered over a period of 7 months at the public slaughterhouse of Patos city, Paraíba state, in the Northeast region of Brazil; 822 animals were inspected for gross lesions of tuberculosis, and 12 (1.46%) had lesions suggestive of tuberculosis in the mammary gland, lungs, liver and mediastinal, mesenteric, submandibular, parotid and prescapular lymph nodes. Presence of granulomatous lesions was confirmed in the submandibular lymph node of one (8.3%) goat at the histopathological examination and at the mycobacterium culture the same sample was confirmed positive. Isolate was confirmed as belonging to the M. tuberculosis complex by PCR restriction enzyme analysis (PRA). Spoligotyping identified the isolate into spoligotype SB0295 on the M. bovis Spoligotype Database website (www.mbovis.org), and it was classified as M. bovis. The occurrence of M. bovis in goats in this study suggests that this species may be a potential source of infection for humans and should be regarded as a possible problem in the advancement of control and eradication program for bovine tuberculosis in Brazil.

Acute Conjunctivitis with Episcleritis and Anterior Uveitis Linked to Adiaspiromycosis and Freshwater Sponges, Amazon Region, Brazil, 2005

Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://www.medscape.com/cme/eidExternal Web Site Icon; (4) view/print certificate. Learning Objectives Upon completion of this activity, participants will be able to: Describe the mechanism of infection for adiaspiromycosis. Identify the age group most susceptible to ocular adiaspiromycosis. Describe presenting symptoms associated with ocular adiaspiromycosis. Describe the frequency of ocular lesions associated with adiaspiromycosis. Identify risk factors for ocular adiaspiromycosis.

Automotive diesel engine transient operation: modeling, optimization and control

Traditionally, the study of internal combustion engines operation has focused on the steady-state performance. However, the daily driving schedule of automotive engines is inherently related to unsteady conditions. There are various operating conditions experienced by (diesel) engines that can be classified as transient. Besides the variation of the engine operating point, in terms of engine speed and torque, also the warm up phase can be considered as a transient condition. Chapter 2 has to do with this thermal transient condition; more precisely the main issue is the performance of a Selective Catalytic Reduction (SCR) system during cold start and warm up phases of the engine. The proposal of the underlying work is to investigate and identify optimal exhaust line heating strategies, to provide a fast activation of the catalytic reactions on SCR. Chapters 3 and 4 focus the attention on the dynamic behavior of the engine, when considering typical driving conditions. The common approach to dynamic optimization involves the solution of a single optimal-control problem. However, this approach requires the availability of models that are valid throughout the whole engine operating range and actuator ranges. In addition, the result of the optimization is meaningful only if the model is very accurate. Chapter 3 proposes a methodology to circumvent those demanding requirements: an iteration between transient measurements to refine a purpose-built model and a dynamic optimization which is constrained to the model validity region. Moreover all numerical methods required to implement this procedure are presented. Chapter 4 proposes an approach to derive a transient feedforward control system in an automated way. It relies on optimal control theory to solve a dynamic optimization problem for fast transients. From the optimal solutions, the relevant information is extracted and stored in maps spanned by the engine speed and the torque gradient.

Quantitative T2 mapping of knee cartilage: differentiation of healthy control cartilage and cartilage repair tissue in the knee with unloading - initial results

Purpose: To prospectively determine on T2 cartilage maps the effect of unloading during a clinical magnetic resonance (MR) examination in the postoperative follow-up of patients after matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint. Materials and Methods: Ethical approval for this study was provided by the local ethics commission, and written informed consent was obtained. Thirty patients (mean age, 35.4 years +/- 10.5) with a mean postoperative follow-up period of 29.1 months +/- 24.4 were enrolled. A multiecho spin-echo T2-weighted sequence was performed at the beginning (early unloading) and end (late unloading) of the MR examination, with an interval of 45 minutes. Mean and zonal region of interest T2 measurements were obtained in control cartilage and cartilage repair tissue. Statistical analysis of variance was performed. Results: The change in T2 values of control cartilage (early unloading, 50.2 msec +/- 8.4; late unloading, 51.3 msec +/- 8.5) was less pronounced than the change in T2 values of cartilage repair tissue (early unloading, 51.8 msec +/- 11.7; late unloading, 56.1 msec +/- 14.4) (P = .024). The difference between control cartilage and cartilage repair tissue was not significant for early unloading (P = .314) but was significant for late unloading (P = .036). Zonal T2 measurements revealed a higher dependency on unloading for the superficial cartilage layer. Conclusion: Our results suggest that T2 relaxation can be used to assess early and late unloading values of articular cartilage in a clinical setting and that the time point of the quantitative T2 measurement affects the differentiation between native and abnormal articular cartilage. (c) RSNA, 2010.

Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop

Invariant Natural Killer T cells (iNKT) are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid-binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR) loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells.