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Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
Atom probe tomography (APT) is rising in influence across many parts of materials science and engineering thanks to its unique combination of highly sensitive composition measurement and three-dimensional microstructural characterization. In this invited article, we have selected a few recent applications that showcase the unique capacity of APT to measure the local composition at structural defects. Whether we consider dislocations, stacking faults, or grain boundary, the detailed compositional measurements tend to indicate specific partitioning behaviors for the different solutes in both complex engineering and model alloys we investigated.
Phosphorus (P) is an essential nutrient in livestock production, involved in most metabolic processes in the body, and with an impact on bone development and growth. Diet supplementation with P can improve productivity, but at excess levels the P utilization can be low, and the high P excretion will lead to environmental pollution (Tamminga, 2003). P supplementation also adds substantially to the cost of feed. Using the isotopic dilution technique (Vitti et al., 2000), we have studied the effect of different P levels in diet on P absorption and excretion in Brazilian sheep, and identified the level at which true P absorption saturates.
HR 6902 was the first target of a systematic study by Griffin (1986, JApA, 7, 195) of binaries showing composite spectra. It is also a well-studied member of the ζ Aur class. ζ Aur systems are long-period eclipsing binaries that are comprised of an evolved giant primary and a hot dwarf companion. Although those component stars have very different effective temperatures they have similar luminosities in the blue and near-UV regions, and hence display a composite spectrum at those wavelengths. In principle the ζ Aur systems are excellent tests of evolutionary and structural stellar models. In recent years the somewhat fragmentary eclipse photometry of HR 6902 has been out-classed by the high-precision continuous monitoring by the space mission CoRoT. HR 6902 was selected as a primary target of its seismology field, because the possible detection of solar-like pulsations in a giant component of a double-lined eclipsing binary could help to calibrate the scaling relation of giant pulsators. Our poster reported the results of a new analysis based on the CoRoT observations and follow-up spectroscopy with HARPS at the ESO 3.6-m telescope at La Silla.
The unprecedented accuracy of the CoRoT photometry enabled us to:
improve drastically the accuracy of the binary orbit and stellar parameters (by a factor ~10 for the radii)
extend the test of validity/calibration of the scaling relations to high stellar mass and radius, and put constraints on the evolutionary state (particularly since this binary is certainly free from tidal effects).
The scaling of turbulent motions is investigated by considering the flow in the eigenframe of the local strain-rate tensor. The flow patterns in this frame of reference are evaluated using existing direct numerical simulations of homogeneous isotropic turbulence over a Reynolds number range from
up to 1131, and also with reference to data for inhomogeneous, anisotropic wall turbulence. The average flow in the eigenframe reveals a shear layer structure containing tube-like vortices and a dissipation sheet, whose dimensions scale with the Kolmogorov length scale,
. The vorticity stretching motions scale with the Taylor length scale,
, while the flow outside the shear layer scales with the integral length scale,
. Furthermore, the spatial organization of the vortices and the dissipation sheet defines a characteristic small-scale structure. The overall size of this characteristic small-scale structure is
in all directions based on the coherence length of the vorticity. This is considerably larger than the typical size of individual vortices, and reflects the importance of spatial organization at the small scales. Comparing the overall size of the characteristic small-scale structure with the largest flow scales and the vorticity stretching motions on the scale of
shows that transitions in flow structure occur where
and 250. Below these respective transitional Reynolds numbers, the small-scale motions and the vorticity stretching motions are progressively less well developed. Scale interactions are examined by decomposing the average shear layer into a local flow, which is induced by the shear layer vorticity, and a non-local flow, which represents the environment of the characteristic small-scale structure. The non-local strain is
in width and height, which is consistent with observations in high Reynolds number flow of a
wide instantaneous shear layer with many
-scale vortical structures inside (Ishihara et al., Flow Turbul. Combust., vol. 91, 2013, pp. 895–929). In the average shear layer, vorticity aligns with the intermediate principal strain at small scales, while it aligns with the most stretching principal strain at larger scales, consistent with instantaneous turbulence. The length scale at which the alignment changes depends on the Reynolds number. When conditioning the flow in the eigenframe on extreme dissipation, the velocity is strongly affected over large distances. Moreover, the associated peak velocity remains Reynolds number dependent when normalized by the Kolmogorov velocity scale. It signifies that extreme dissipation is not simply a small-scale property, but is associated with large scales at the same time.
Plants’ ability to rebuild their tiller population is affected by weather changes and management strategies. The hypothesis of the present study was that frequency and severity of defoliation alter Mulato grass (Brachiaria ruziziensis × Brachiaria brizantha cv. Marandu) sward development, and the proportion of aerial and basal tillers, interfering with sward stability. The objective was to evaluate aerial, basal and total tiller population density and changes in tillering dynamics. Treatments corresponded to strategies of rotational grazing characterized by combinations between two pre-grazing (95% and maximum canopy light interception during regrowth; LI95% and LIMax) and two post-grazing conditions (15 and 20 cm stubble height). The experimental period comprised four seasons of the year: summer 2008 (February–March 2008); autumn–early spring (April to mid-November 2008); late spring (mid-November–December 2008); and summer 2009 (January–March 2009). Density of aerial tillers decreased from summer 2008 to late spring. Tiller death decreased from summer 2008 to autumn–early spring. Aerial and total tiller death increased from late spring to summer 2009, mainly for the LI95% treatment. No differences were observed in the tiller population stability index of aerial tillers for LI treatments or post-grazing heights. The balance between tiller appearance and death for basal tillers remained relatively stable from summer 2008 to late spring. For aerial tillers the balance decreased to negative values from summer 2008 to autumn–early spring for both LI treatments. For total tiller population, the balance decreased to negative values from summer 2008 to autumn–early spring. Results indicated a strong seasonal effect on Mulato grass tillering and growth. Tillering dynamics were affected primarily by grazing frequency, which changed the relative importance of basal and aerial tillers. The results suggested that basal tillering was the predominant perennation pathway.
To date, only a few sporadic cases of infections due to Klebsiella pneumoniae carbapenemase (KPC) producers have been reported in Portugal. Here, we report for the first time an outbreak of K. pneumoniae KPC-3 producers in a tertiary-care hospital during 2013. Twenty-seven ertapenem-resistant K. pneumoniae were identified in patients at a tertiary-care hospital during 2013 isolated predominantly from urine (48·1%) and blood (25·9%) cultures. All isolates were highly resistant to β-lactam antibiotics and most showed intermediate resistance to imipenem. The more frequent β-lactamases were TEM- (77·7%), CTX-M- (70·3%) and KPC-type (66·6%). KPC-3 was identified by sequencing. The blaKPC−3 gene was associated with an IncF plasmid, and efficiently transferred to E. coli J53. Pulsed-field gel electrophoresis typing revealed three clusters of isolates which were further characterized by multi-locus sequence typing as ST11, ST15 and ST348. Ertapenem-resistant ST15 was already in circulation in the hospital, related to expression of OmpK36 modified porin, but the other two sequence types had not been previously found in the hospital. We conclude that the IncF plasmid mediated transfer of KPC-3 in the outbreak and that implementation of carbapenemase gene screening in isolates from patients on admission to hospital is advisable in order to control dissemination of these antimicrobial resistance elements.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors.
Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC.
Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA.
UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.
Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL−1 concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0·05 mg mL−1. The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.
Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.
Firstly, a brief overview will be given on different models that are able to describe the behaviour of wave propagation as a function of specific frequency ranges. Each range corresponds to different heating systems, namely, 20–100 MHz for the ion cyclotron resonant heating, 2–20 GHz for lower-hybrid heating or current drive, and 100–250 GHz for electron cyclotron resonant heating or current drive systems. The specification of every system will be explained in detail, including the typical set of equations and the assumptions needed to describe the properties of these heating or current drive systems, as well as their specific domains of validity. In these descriptions, special attention will be paid to the boundary conditions. A review of specific physical problems associated with the wave heating systems will also be provided. The review will detail the role of simulation in answering questions that arise from experiments on magnetized plasma devices devoted to fusion. A few examples that will be covered are the impact of edge turbulence on wave propagation and its consequences on heating system performance, the effects of fast particles and ponderomotive effects, among others. A study that is more focused on radio-frequency sheath effects will also be discussed. It shows that such simulations require very sophisticated tools to gain a partial understanding of the observations undertaken in dedicated experiments. To conclude this review, an overview will be given about the requirements and progress necessary to obtain relevant predictive simulation tools able to describe the wave heating systems used in fusion devices.
The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.
The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0–∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.
The Bench 19 Bonebed at Bentiaba, Angola, is a unique concentration of marine vertebrates preserving six species of mosasaurs in sediments best correlated by magnetostratigraphy to chron C32n.1n between 71.4 and 71.64 Ma. The bonebed formed at a paleolatitude near 24°S, with an Atlantic width at that latitude approximating 2700 km, roughly half that of the current width. The locality lies on an uncharacteristically narrow continental shelf near transform faults that controlled the coastal outline of Africa in the formation of the South Atlantic Ocean. Biostratigraphic change through the Bentiaba section indicates that the accumulation occurred in an ecological time dimension within the 240 ky bin delimited by chron 32n.1n. The fauna occurs in a 10 m sand unit in the Mocuio Formation with bones and partial skeletons concentrated in, but not limited to, the basal 1–2 m. The sediment entombing the fossils is an immature feldspathic sand shown by detrital zircon ages to be derived from nearby granitic shield rocks. Specimens do not appear to have a strong preferred orientation and they are not concentrated in a strand line. Stable oxygen isotope analysis of associated bivalve shells indicates a water temperature of 18.5°C. The bonebed is clearly mixed with scattered dinosaur and pterosaur elements in a marine assemblage. Gut contents, scavenging marks and associated shed shark teeth in the Bench 19 Fauna indicate biological association and attrition due to feeding activities. The ecological diversity of mosasaur species is shown by tooth and body-size disparity and by δ13C analysis of tooth enamel, which indicate a variety of foraging areas and dietary niches. The Bench 19 Fauna was formed in arid latitudes along a coastal desert similar to that of modern Namibia on a narrow, tectonically controlled continental shelf, in shallow waters below wave base. The area was used as a foraging ground for diverse species, including molluscivorus Globidens phosphaticus, small species expected near the coast, abundant Prognathodon kianda, which fed on other mosasaurs at Bench 19, and species that may have been transient and opportunistic feeders in the area.
We describe the preliminary design of a magnetograph and visible-light imager instrument to study the solar dynamo processes through observations of the solar surface magnetic field distribution. The instrument will provide measurements of the vector magnetic field and of the line-of-sight velocity in the solar photosphere. As the magnetic field anchored at the solar surface produces most of the structures and energetic events in the upper solar atmosphere and significantly influences the heliosphere, the development of this instrument plays an important role in reaching the scientific goals of The Atmospheric and Space Science Coordination (CEA) at the Brazilian National Institute for Space Research (INPE). In particular, the CEA's space weather program will benefit most from the development of this technology. We expect that this project will be the starting point to establish a strong research program on Solar Physics in Brazil. Our main aim is acquiring progressively the know-how to build state-of-the-art solar vector magnetograph and visible-light imagers for space-based platforms to contribute to the efforts of the solar-terrestrial physics community to address the main unanswered questions on how our nearby Star works.
Selection of Quarter Horses for different purposes has led to the formation of lines, including racing and cutting horses. The objective of this study was to identify genomic regions divergently selected in racing line of Quarter Horses in relation to cutting line applying relative extended haplotype homozygosity (REHH) analysis, an extension of extended haplotype homozygosity (EHH) analysis, and the fixation index (FST) statistic. A total of 188 horses of both sexes, born between 1985 and 2009 and registered at the Brazilian Association of Quarter Horse Breeders, including 120 of the racing line and 68 of the cutting line, were genotyped using single nucleotide polymorphism arrays. On the basis of 27 genomic regions identified as selection signatures by REHH and FST statistics, functional annotations of genes were made in order to identify those that could have been important during formation of the racing line and that could be used subsequently for the development of selection tools. Genes involved in muscle growth (n=8), skeletal growth (n=10), muscle energy metabolism (n=15), cardiovascular system (n=14) and nervous system (n=23) were identified, including the FKTN, INSR, GYS1, CLCN1, MYLK, SYK, ANG, CNTFR and HTR2B.
Euclid is the next ESA mission devoted to cosmology. It aims at observing most of the extragalactic sky, studying both gravitational lensing and clustering over ~15,000 square degrees. The mission is expected to be launched in year 2020 and to last six years. The sheer amount of data of different kinds, the variety of (un)known systematic effects and the complexity of measures require efforts both in sophisticated simulations and techniques of data analysis. We review the mission main characteristics, some aspects of the the survey and highlight some of the areas of interest to this meeting.
The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.
Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.
Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.
Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.