Failure to Recover from Proactive Semantic Interference Differentiates Amnestic Mild Cognitive Impairment and PreMCI from Normal Aging after Adjusting for Initial Learning Ability

Background: There is increasing evidence that the failure to recover from proactive semantic interference (frPSI) may be an early cognitive marker of preclinical Alzheimer’s disease (AD). However, it is unclear whether frPSI effects reflect deficiencies in an individual’s initial learning capacity versus the actual inability to learn new semantically related targets. Objective: The current study was designed to adjust for learning capacity and then to examine the extent to which frPSI, proactive semantic interference (PSI) and retroactive semantic interference (RSI) effects could differentiate between older adults who were cognitively normal (CN), and those diagnosed with either Pre-Mild Cognitive Impairment (PreMCI) or amnestic MCI (aMCI). Methods: We employed the LASSI-L cognitive stress test to examine frPSI, PSI and RSI effects while simultaneously controlling for the participant’s initial learning capacity among 50 CN, 35 aMCI, and 16 PreMCI participants who received an extensive diagnostic work-up. Results: aMCI and PreMCI participants showed greater frPSI deficits (50% and 43.8% respectively) compared to only 14% of CNparticipants. PSI effects were observed for aMCI but not PreMCI participants relative to their CN counterparts. RSI failed to differentiate between any of the study groups. Conclusion: By using participants as their own controls and adjusting for overall learning and memory, it is clear that frPSI deficits occur with much greater frequency in individuals at higher risk for Alzheimer’s disease (AD), and likely reflect a failure of brain compensatory mechanisms.Fil: Curiel, Rosie E.. University of Miami; Estados UnidosFil: Crocco, Elizabeth A.. University of Miami; Estados UnidosFil: Raffo, Arlene. University of Miami; Estados UnidosFil: Guinjoan, Salvador Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Nemeroff, Charles B.. University of Miami; Estados UnidosFil: Penate, Ailyn. Mount Sinai Medical Center; Estados Unidos. University of Miami; Estados UnidosFil: Piña, Daema. University of Miami; Estados UnidosFil: Loewenstein, David A.. Mount Sinai Medical Center; Estados Unidos. University of Miami; Estados Unido

Thermoregulation in captive broad-snouted caiman (Caiman latirostris)

Background: Crocodilians are ectothermic animals. For this reason, the environmental temperature has substantial effects on their physiology and behavior. The thermoregulatory behavior of these animals involves the selective use of different types of environments. This behavior enables them to reach the temperature level for their metabolic activities. This study aimed to determine the influence of sex, body size, and reproductive stage on the body temperature (T b) of adult broad-snouted caiman (Caiman latirostris) in captivity. Thermal sensors were surgically implanted in the peritoneal cavity of 16 adult females and 4 adult males and programmed to register T b hourly during 6 months. Results: The diel T b pattern of the broad-snouted caiman reflected the variation among the microenvironmental temperatures used by the species (water surface, pool bottom, and ground). The sex of the animals had influence on their T b, but body size did not. Reproductive females had higher T b than non-reproductive females during October to early November. It is possible that this difference is a result of the ovulation period of the species. Sick animals appeared to show behavioral fever. Conclusions: The results of the present study suggest that several factors can affect the T b of adult broad-snouted caiman in captivity. Future studies should focus on the possible effect of thermoregulatory behavior on individuals' growth rate and reproductive performance.Fil: Bassetti, Luís A. B.. Universidade de Sao Paulo; BrasilFil: Marques, Thiago S.. Universidade de Sao Paulo; BrasilFil: Malvásio, Adriana. Universidade Federal do Tocantins; BrasilFil: Piña, Carlos Ignacio. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentina. Universidad Autónoma de Entre Ríos. Facultad de Ciencia y Tecnología; Argentina. Universidad Nacional de Entre Ríos. Facultad de Ciencias de la Alimentación; ArgentinaFil: Verdade, Luciano M.. Universidade de Sao Paulo; Brasi

A dust disk surrounding the young A star HR4796A

We report the codiscovery of the spatially-resolved dust disk of the Vega-like star HR 4796A. Images of the thermal dust emission at $\lambda = 18 \mu$m show an elongated structure approximately 200 AU in diameter surrounding the central A0V star. The position angle of the disk, $30^{\circ} \pm 10^{\circ}$, is consistent to the position angle of the M companion star, $225^{\circ}$, suggesting that the disk-binary system is being seen nearly along its orbital plane. The surface brightness distribution of the disk is consistent with the presence of an inner disk hole of approximately 50 AU radius, as was originally suggested by Jura et al. on the basis of the infrared spectrum. HR 4796 is a unique system among the Vega-like or $\beta$ Pictoris stars in that the M star companion (a weak-emission T Tauri star) shows that the system is relatively young, $\sim 8 \pm 3$ Myr. The inner disk hole may provide evidence for coagulation of dust into larger bodies on a timescale similar to that suggested for planet formation in the solar system.Comment: 12 pages, 3 PostScript figures, accepted for publication in Astrophysical Journal Letter

Mid-infrared imaging of the young binary star Hen 3-600: Evidence for a dust disk around the primary

We present high-resolution mid-infrared observations of the nearby late-type young binary system Hen 3-600. The binary, at a distance of $\sim$ 50 pc, could be a member of the TW Hydrae Association, the nearest known group of young stars, with an age of a few million years. Our images make it possible for the first time to determine which star in the pair, separated by 1.4'', harbors the mid-infrared excess detected by IRAS. In the near-infrared, where the radiation is primarily photospheric, Hen 3-600A (M3) and Hen 3-600B (M3.5) have a flux ratio of 1.6. At 4.8$\mu$m, 10.8$\mu$m, and 18.2$\mu$m, the primary becomes increasingly dominant over the secondary, suggesting that most of the circumstellar dust in the system resides around Hen 3-600A. Comparison of the spectral energy distribution (SED) of Hen 3-600A to the median SED of classical T Tauri stars suggests that its disk may be truncated by the secondary and provides tentative evidence for a central disk hole. The distribution of dust in the Hen 3-600 system may provide important clues to the formation and evolution of protoplanetary disks in close binaries.Comment: 9 pages, 2 PostScript figures, accepted for publication in The Astrophysical Journal Letter

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

SORLA attenuates EphA4 signaling and amyloid, β-induced neurodegeneration

Sortilin-related receptor with LDLR class A repeats (SORLA, SORL1, or LR11) is a genetic risk factor associated with Alzheimer's disease (AD). Although SORLA is known to regulate trafficking of the amyloid {beta} (A{beta}) precursor protein to decrease levels of proteotoxic A{beta} oligomers, whether SORLA can counteract synaptic dysfunction induced by A{beta} oligomers remains unclear. Here, we show that SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1 ligand-induced EphA4 clustering and activation to limit downstream effects of EphA4 signaling in neurons. Consistent with these findings, SORLA transgenic mice, compared with WT mice, exhibit decreased EphA4 activation and redistribution to postsynaptic densities, with milder deficits in long-term potentiation and memory induced by A{beta} oligomers. Importantly, we detected elevated levels of active EphA4 in human AD brains, where EphA4 activation is inversely correlated with SORLA/EphA4 association. These results demonstrate a novel role for SORLA as a physiological and pathological EphA4 modulator, which attenuates synaptotoxic EphA4 activation and cognitive impairment associated with A{beta}-induced neurodegeneration in AD

Life cycle of Amblyomma mixtum (Acari: Ixodidae) parasitizing different hosts under laboratory conditions.

Amblyomma mixtum is a tick species in the Amblyomma cajennense complex. The known geographic range of A. mixtum extends from Texas in theUSAto western Ecuador and some islands in the Caribbean. Amblyomma mixtum is a vector of disease agents of veterinary and public health importance. The objective of this study was to describe the life cycle of A. mixtum under laboratory conditions. Bovines, rabbits and sheep were infested with larvae, nymphs, and adult ticks under controlled conditions to assess several biological parameters. Eggs, larvae, nymphs and adults were kept in an incubator (27 C temperature and 80% relative humidity) when they were off the host. The average life cycle of A. mixtum was 88 and 79 days when fed on rabbits and cattle, respectively. Sheep were found to be unsuitable because no ticks attached. The rabbit is a more practical host to maintain a colony of A. mixtum under laboratory conditions. The data from this study can be considered as an example for the life cycle of A. mixtum. However, caution must be exercised when making comparisons to the biology of A. mixtum in its natural habitat

Estudo de gerenciamento de riscos em contratos de concessão rodoviária

O objetivo é posicionar a maturidade do gerenciamento de riscos de concessões rodoviárias e comparar o modo de alocação de risco com o de outros países. Esta avaliação será realizada por meio da análise dos contratos de concessão de rodovias existentes, comparando etapas de concessões brasileiras entre si e internacionalmente. Como resultado, pode-se perceber que apesar do crescimento da maturidade na alocação e posicionamento dos riscos, ainda não existe um gerenciamento dos mesmos sendo realizado, o que promove reajustes extraoficiais dos preços de pedágio em excesso e o acúmulo de aditivos. Não serão abordadas soluções, sendo limitação deste trabalho.Concessions are recurrent in the civil construction sector, especially in infrastructure works. One of the Brazilian sectors that most benefits from this form of contract is the road sector. Despite widespread use, managing the contractual risk of concessions is still an issue and promotes numerous disputes between contract stakeholders. This study focuses on the risk management used by the public regulatory agency of road concessions, aiming to position the maturity of the risk management of this agency and to compare risk allocation to other countries. This evaluation was carried out by analyzing the existing highway concession contracts, comparing the stages of Brazilian concessions among themselves and also with international references of the Mundial Bank. Also, ANTT maturity stage was established by the use of a maturity matrix. The reached conclusion is that although there was a maturity growth in the allocation and positioning of the risks along the national contracts, there is still no risk management being carried out by the public initiative, which promotes extra-official readjustments of toll prices and the accumulation of additives

Low thrust propulsion in a coplanar circular restricted four body problem

This paper formulates a circular restricted four body problem (CRFBP), where the three primaries are set in the stable Lagrangian equilateral triangle configuration and the fourth body is massless. The analysis of this autonomous coplanar CRFBP is undertaken, which identies eight natural equilibria; four of which are close to the smaller body, two stable and two unstable, when considering the primaries to be the Sun and two smaller bodies of the solar system. Following this, the model incorporates `near term' low-thrust propulsion capabilities to generate surfaces of articial equilibrium points close to the smaller primary, both in and out of the plane containing the celestial bodies. A stability analysis of these points is carried out and a stable subset of them is identied. Throughout the analysis the Sun-Jupiter-Asteroid-Spacecraft system is used, for conceivable masses of a hypothetical asteroid set at the libration point L4. It is shown that eight bounded orbits exist, which can be maintained with a constant thrust less than 1:5 10􀀀4N for a 1000kg spacecraft. This illustrates that, by exploiting low-thrust technologies, it would be possible to maintain an observation point more than 66% closer to the asteroid than that of a stable natural equilibrium point. The analysis then focusses on a major Jupiter Trojan: the 624-Hektor asteroid. The thrust required to enable close asteroid observation is determined in the simplied CRFBP model. Finally, a numerical simulation of the real Sun-Jupiter-624 Hektor-Spacecraft is undertaken, which tests the validity of the stability analysis of the simplied model