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1.
Proc Natl Acad Sci U S A ; 120(7): e2210953120, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36745812

RESUMO

Opioid use produces enduring associations between drug reinforcement/euphoria and discreet or diffuse cues in the drug-taking environment. These powerful associations can trigger relapse in individuals recovering from opioid use disorder (OUD). Here, we sought to determine whether the epigenetic enzyme, histone deacetylase 5 (HDAC5), regulates relapse-associated behavior in an animal model of OUD. We examined the effects of nucleus accumbens (NAc) HDAC5 on both heroin- and sucrose-seeking behaviors using operant self-administration paradigms. We utilized cre-dependent viral-mediated approaches to investigate the cell-type-specific effects of HDAC5 on heroin-seeking behavior, gene expression, and medium spiny neuron (MSN) cell and synaptic physiology. We found that NAc HDAC5 functions during the acquisition phase of heroin self-administration to limit future relapse-associated behavior. Moreover, overexpressing HDAC5 in the NAc suppressed context-associated and reinstated heroin-seeking behaviors, but it did not alter sucrose seeking. We also found that HDAC5 functions within dopamine D1 receptor-expressing MSNs to suppress cue-induced heroin seeking, and within dopamine D2 receptor-expressing MSNs to suppress drug-primed heroin seeking. Assessing cell-type-specific transcriptomics, we found that HDAC5 reduced expression of multiple ion transport genes in both D1- and D2-MSNs. Consistent with this observation, HDAC5 also produced firing rate depression in both MSN classes. These findings revealed roles for HDAC5 during active heroin use in both D1- and D2-MSNs to limit distinct triggers of drug-seeking behavior. Together, our results suggest that HDAC5 might limit relapse vulnerability through regulation of ion channel gene expression and suppression of MSN firing rates during active heroin use.


Assuntos
Cocaína , Heroína , Camundongos , Animais , Camundongos Transgênicos , Heroína/metabolismo , Heroína/farmacologia , Cocaína/farmacologia , Reforço Psicológico , Comportamento de Procura de Droga/fisiologia , Epigênese Genética , Núcleo Accumbens/fisiologia , Autoadministração
2.
J Environ Manage ; 358: 120696, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614003

RESUMO

The offshore Multi-use Setting (MUS) is a concept that aims to co-locate marine industrial activities, including wind farms and aquaculture. MUS is considered an innovative approach to promoting efficiency in space and resource use whilst contributing global policy priorities. However, the impacts of MUS development across social, economic, and environmental domains are uncertain, hindering the commercialisation of the concept. In this study, we initially demonstrate the potential consequences of co-locating seaweed aquaculture and a wind farm as a step towards MUS. Using a hypothetical case study and modified Delphi methodology, 14 subject matter experts predicted potential outcomes across social and environmental objectives. Five Cognitive maps and impact tables of 58 potential consequences were generated based on experts' perspective on co-locating seaweed aquaculture and a wind farm. The findings highlight the potential to exasperate pressures in the area, including those already attributed to wind farm operations, such as species mortality and stakeholder conflict. However, it may also enhance social-ecological conditions, such as resource provisioning and promoting habitat functionality in the region, through the addition of seaweed aquaculture. The cognitive maps demonstrate the complexity of managing MUS implementation, where high degree of variability and uncertainty about the outcomes is present. The findings of this study provide the vital entry point to performing further integrative assessment and modelling approaches, such as probabilistic analysis and simulations, in support of MUS decision-making. The research also strongly recommends alternative strategies in the pursuit of combining seaweed production and wind farms to avoid significant financial (among many other) trade-offs and risks. More broadly, we have found that our approach's ability to visually represent a complex situation while considering multiple objectives could be immensely valuable for other bioeconomy innovations or nature-based solutions. It helps mitigate the potential for expensive investments without a comprehensive evaluation of the associated risks and negative impacts, as necessitated by the principles of sustainability in decision-making.


Assuntos
Aquicultura , Alga Marinha , Vento , Incerteza , Conservação dos Recursos Naturais/métodos , Ecossistema
3.
Transp Res Rec ; 2677(4): 51-64, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37153176

RESUMO

The New York City metropolitan area was hard hit by COVID-19, and the pandemic brought with it unprecedented challenges for New York City Transit. This paper addresses the techniques used to estimate dramatically changing ridership, at a time when previously dependable sources suddenly became unavailable (e.g., local bus payment data, manual field checks). The paper describes alterations to ridership models, as well as the expanding use of automated passenger counters, including validation of new technology and scaling to account for partial data availability. The paper then examines the trends in subway and bus ridership. Peak periods shifted by both time of day and relative intensity compared with the rest of the day, but not in the same way on weekdays and weekends. On average, trip distances became longer for subway and local bus routes, but overall average bus trip distances decreased owing to a drop in express bus usage. Subway ridership changes were compared with neighborhood demographic statistics and numerous correlations were identified, including with employment, income, and race and ethnicity. Other factors, such as the presence of hospitals, were not found to be significant.

4.
Mol Biol Evol ; 38(9): 3724-3736, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-33950261

RESUMO

The impact of human-mediated environmental change on the evolutionary trajectories of wild organisms is poorly understood. In particular, capacity of species to adapt rapidly (in hundreds of generations or less), reproducibly and predictably to extreme environmental change is unclear. Silene uniflora is predominantly a coastal species, but it has also colonized isolated, disused mines with phytotoxic, zinc-contaminated soils. To test whether rapid, parallel adaptation to anthropogenic pollution has taken place, we used reduced representation sequencing (ddRAD) to reconstruct the evolutionary history of geographically proximate mine and coastal population pairs and found largely independent colonization of mines from different coastal sites. Furthermore, our results show that parallel evolution of zinc tolerance has occurred without gene flow spreading adaptive alleles between mine populations. In genomic regions where signatures of selection were detected across multiple mine-coast pairs, we identified genes with functions linked to physiological differences between the putative ecotypes, although genetic differentiation at specific loci is only partially shared between mine populations. Our results are consistent with a complex, polygenic genetic architecture underpinning rapid adaptation. This shows that even under a scenario of strong selection and rapid adaptation, evolutionary responses to human activities (and other environmental challenges) may be idiosyncratic at the genetic level and, therefore, difficult to predict from genomic data.


Assuntos
Metais Pesados , Adaptação Fisiológica/genética , Ecótipo , Poluição Ambiental , Deriva Genética , Humanos , Metais Pesados/análise
5.
Cereb Cortex ; 30(3): 1957-1973, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-31647525

RESUMO

Prior knowledge about our environment influences our actions. How does this knowledge evolve into a final action plan and how does the brain represent this? Here, we investigated this question in the monkey oculomotor system during self-guided search of natural scenes. In the frontal eye field (FEF), we found a subset of neurons, "Early neurons," that contain information about the upcoming saccade long before it is executed, often before the previous saccade had even ended. Crucially, much of this early information did not relate to the actual saccade that would eventually be selected. Rather, it related to prior information about the probabilities of possible upcoming saccades based on the presaccade fixation location. Nearer to the time of saccade onset, a greater proportion of these neurons' activities related to the saccade selection, although prior information continued to influence activity throughout. A separate subset of FEF neurons, "Late neurons," only represented the final action plan near saccade onset and not prior information. Our results demonstrate how, across the population of FEF neurons, prior information evolves into definitive saccade plans.


Assuntos
Atenção/fisiologia , Lobo Frontal/fisiologia , Memória/fisiologia , Campos Visuais/fisiologia , Percepção Visual/fisiologia , Potenciais de Ação/fisiologia , Animais , Fixação Ocular/fisiologia , Neurônios/fisiologia , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia
6.
Am J Emerg Med ; 45: 92-99, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33677266

RESUMO

OBJECTIVE: To describe the impact of a novel communication and triage pathway called fast track dialysis (FTD) on the length of stay (LOS), resource utilization, and charges for unscheduled hemodialysis for end stage renal disease (ESRD) patients presenting to the emergency department (ED). METHODS: Prospective and retrospective cohorts of ESRD patients meeting requirements of routine or urgent hemodialysis at a tertiary academic hospital from September 25th, 2016 to September 25th, 2018 in 1 year cohorts. Two sample t-tests were used to compare most outcomes of the cohorts with a Mann-Whitney U test used for skewed data. Nephrology group outcomes were analyzed by two-way ANOVA and Kruskal-Wallis and chi-square tests. RESULTS: There were 98 encounters in the historical cohort and 143 encounters in the fast track dialysis cohort. FTD had significantly lowered median ED LOS (4.05 h, vs 5.3 h, p < 0.001), median hospital LOS (12.8 h vs 27 h, p < 0.001), time to hemodialysis (4.78 h vs 7.29 h, p < 0.001), and median hospital charges ($26,040 vs $30,747, p < 0.016). The FTD cohort had increased 30 day ED return for each encounter compared to the historical cohort (1.85 visits vs 0.73 visits, p < 0.001), however no significant increase in 1 year ED visits (6.52 visits vs 5.80, p = 0.4589) or 1 year readmissions (5.89 readmissions vs 4.81 readmissions, p = 0.3584). Most nephrology groups had significantly lower time to hemodialysis order placement and time to start hemodialysis. CONCLUSION: A multidisciplinary approach with key stakeholders using a standard pathway can lead to improved efficiency in throughput, reduced charges, and hospital resource utilization for patients needing urgent or routine hemodialysis. A study with a dedicated geographic observation unit for protocolized short stay patients including conditions ranging from low risk chest pain to transient ischemic events that incorporates FTD patients under this protocol should be considered.


Assuntos
Serviço Hospitalar de Emergência/normas , Falência Renal Crônica/terapia , Diálise Renal , Tempo para o Tratamento , Feminino , Preços Hospitalares/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Melhoria de Qualidade , Estudos Retrospectivos , Triagem
7.
Clin Infect Dis ; 71(2): 249-255, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31437276

RESUMO

BACKGROUND: The HIV Prevention Trials Network (HPTN) 067/Alternative Dosing to Augment PrEP Pill Taking (ADAPT) Study evaluated the feasibility of daily and nondaily human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens. METHODS: An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the preexposure prophylaxis initiative (iPrEx) trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use. RESULTS: We estimated that PrEP was highly protective (85%-96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%-88% efficacy) than in Harlem (62%-81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85%, and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8-9 percentage points in Harlem and by 5-9 percentage points in Bangkok across regimens. CONCLUSIONS: Our analysis suggests that PrEP was more effective among MSM in Thailand than in the United States as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, nondaily PrEP was less effective than daily PrEP, especially in the United States where the sex act coverage associated with daily use was substantially higher.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , New York , Tailândia , Estados Unidos
8.
J Urol ; 202(4): 757-762, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31120374

RESUMO

PURPOSE: We report long-term data on a large cohort of adults who underwent formation of a continent catheterizable channel for various indications. We examined outcomes according to the tissue used for channel formation. MATERIALS AND METHODS: We retrospectively reviewed the case notes of 176 consecutive adult patients in whom a continent catheterizable channel was created using the Mitrofanoff principle for a broad range of indications a median of 142 months (range 54 to 386) previously. We evaluated outcomes in terms of continued use and continence for each type of material used for channel formation. RESULTS: At the time of this review 165 of the 173 patients (95.4%) included in this study were alive. We included 114 women (65.9%) and 59 men (34.1%) who underwent surgery at a median age of 42 years (range 18 to 73) with a mean followup of 78.6 months (median 60, range 2 to 365). The rate of revision for all causes was higher in the ileal group than in the group with an appendiceal channel (channel stenosis rate 22.7% vs 17.2%, p = 0.39, and channel incontinence rate 36.0% vs 19.5%, p = 0.03). Although 38.7% of patients underwent major surgical revision of the channel at some point, 75.9% of channels continued to be used, of which 90.2% were continent. CONCLUSIONS: This study provides a pragmatic overview of the outcome of these challenging cases. Mitrofanoff channel formation represents a durable technique. Appendix and ileum are each a viable choice for tissue use. Tissue selection depends on availability and individual patient factors.


Assuntos
Apêndice/transplante , Íleo/transplante , Cateterismo Urinário/métodos , Coletores de Urina , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Cateterismo Urinário/efeitos adversos , Transtornos Urinários/etiologia , Transtornos Urinários/cirurgia , Adulto Jovem
9.
Emerg Radiol ; 26(2): 161-168, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30443737

RESUMO

PURPOSE: To identify and characterize the most frequent users of emergency department (ED) imaging. MATERIALS AND METHODS: All patients with at least one ED visit in 2016 across a four-hospital healthcare system were retrospectively identified and their ED imaging utilization characterized. RESULTS: Overall, 126,940 unique patients underwent 187,603 ED visits (mean 1.5 ± 1.7) and a total of 192,142 imaging examinations (mean 1.7 ± 2.7). Fifty-eight percent of patients were imaged (73,672) and underwent a mean 2.6 ± 2.7 exams. When ranked by ED visits, 1.6% (2007) of patients had ≥ 4 ED visits (mean 6.1 ± 5.4). These ED "clinical superusers" accounted for 7.7% (14,409) of total ED visits and underwent 6.8 ± 5.4 imaging examinations, while non-superusers underwent 1.5 ± 2.2 (p < 0.01). When ranked by ED imaging utilization, 12.3% (15,575) of patients underwent ≥ 4 ED imaging examinations and consumed 49.5% (95,053) of all imaging services. A subset of just 1.3% (1608) of ED patients underwent > 10 annual ED examinations (ED "imaging superusers") and accounted for 12.4% (23,787) of all ED imaging services. Only 0.4% (n = 472) of patients were both clinical and imaging superusers. Despite similar ED visits to clinical superusers (6.0 ± 5.6 vs. 6.1 ± 5.4, p = 0.92), imaging superusers underwent significantly more imaging (14.8 ± 4.8 vs. 6.8 ± 5.4 examinations, p < 0.01). CONCLUSION: Just 12% of ED patients consume 50% of all ED imaging services, and 1.3% consume 12.4%. These ED imaging superusers represent a distinct group from clinical superusers. Prospective identification of this newly described subgroup might permit targeted interventions to control ED imaging volume, restrain costs, and minimize per-patient radiation exposure.


Assuntos
Diagnóstico por Imagem/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Revisão da Utilização de Recursos de Saúde
10.
Allergy Asthma Proc ; 39(5): 365-370, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30107868

RESUMO

BACKGROUND: The first subcutaneous (SC) C1-esterase inhibitor concentrate (C1-INH) was approved by the U.S. Food and Drug Administration in June 2017 as routine prophylaxis to prevent hereditary angioedema attacks in adolescents and adults at a dose of 60 IU/kg twice weekly based on the phase III Clinical Study for Optimal Management of Preventing Angioedema With Low-volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT) trial. OBJECTIVE: This article aimed to evaluate the relationship of the C1-INH (SC) dose regimens tested in the COMPACT trial (40 IU/kg and 60 IU/kg twice weekly) and the occurrence of adverse events (AEs). METHODS: Patients were instructed to record any AEs in their e-diary daily. Safety and tolerability were assessed based on reported AEs, including injection-site reactions (ISRs); unsolicited AEs (AEs other than ISRs); serious AEs; thrombotic, thromboembolic, anaphylactic, hypersensitivity, sepsis, and bacteremia events; inhibitory antibodies to C1-INH; and clinically significant abnormalities in laboratory assessments. Information on ISRs was specifically solicited. RESULTS: No relationship between the dose of C1-INH (SC) and the incidence of ISRs or unsolicited AEs was observed. The proportion of injections followed by at least one ISR was 12% with C1-INH (SC) 40 IU/kg versus 5% with 60 IU/kg and 6% with placebo. No ISRs were serious or led to treatment discontinuation, and all resolved. There were no anaphylaxis, thromboembolic, sepsis, or bacteremia events reported during treatment with C1-INH (SC). All hypersensitivity AEs were nonserious, and the majority were assessed as being unrelated to treatment. No inhibitory antibodies to C1-INH were observed. CONCLUSION: C1-INH (SC) is safe and well tolerated with no dose-dependent safety concerns, as demonstrated in the COMPACT trial.Clinical trial NCT01912456, www.clinicaltrials.gov.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Angioedemas Hereditários/complicações , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/prevenção & controle , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Progressão da Doença , Hipersensibilidade a Drogas/etiologia , Feminino , Humanos , Masculino , Sepse/etiologia , Índice de Gravidade de Doença , Tromboembolia/etiologia , Resultado do Tratamento
11.
J Strength Cond Res ; 32(1): 105-112, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27806003

RESUMO

Wood, DJ, Coughlan, GF, and Delahunt, E. Fitness profiles of elite adolescent Irish rugby union players. J Strength Cond Res 32(1): 105-112, 2018-Rugby unions throughout the world are implementing player development models to prepare young players to meet the demands of professional rugby union. An example of this is the Irish Rugby Football Union Long Term Player Development model. The purpose of this study was to provide normative data relating to the physical fitness of elite adolescent Irish rugby union players and determine the differences in the physical capacities between players in the forward and back units as well as to provide descriptive data for the position categorizations within these units for this unique population. Players in the forward unit were significantly taller and heavier than players in the back unit (1.85 ± 0.06 m and 96.88 ± 9.00 kg vs. 1.79 ± 0.05 m and 81.97 ± 7.09 kg, respectively). Forwards (38.37 ± 4.00 cm) had a significantly lower countermovement jump height than backs (41.31 ± 4.44 cm). Forwards had a significantly lower triple hop for the distance score on their right (5.78 ± 0.52 m) and left (5.78 ± 0.55 m) legs compared with backs (6.26 ± 0.42 m and 6.33 ± 0.45 m, respectively). Forwards (1.85 ± 0.07 seconds) had a significantly higher 10-m sprint time than backs (1.77 ± 0.06 seconds). Furthermore, forwards (675.90 ± 82.46 m) had a significantly lower 150-m shuttle test score than backs (711.71 ± 27.46 m). The results of this study provide normative data for players who currently possess underage international potential and could be used by strength and conditioning coaches to guide the selection of players through talent identification processes.


Assuntos
Atletas , Desempenho Atlético/fisiologia , Futebol Americano/fisiologia , Aptidão Física/fisiologia , Adolescente , Pesos e Medidas Corporais , Humanos , Irlanda , Masculino , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Adulto Jovem
12.
J Neurosci ; 36(31): 8273-82, 2016 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-27488645

RESUMO

UNLABELLED: The appearance of a novel visual stimulus generates a rapid stimulus-locked response (SLR) in the motor periphery within 100 ms of stimulus onset. Here, we recorded SLRs from an upper limb muscle while humans reached toward (pro-reach) or away (anti-reach) from a visual stimulus. The SLR on anti-reaches encoded the location of the visual stimulus rather than the movement goal. Further, SLR magnitude was attenuated when subjects reached away from rather than toward the visual stimulus. Remarkably, SLR magnitudes also correlated with reaction times on both pro-reaches and anti-reaches, but did so in opposite ways: larger SLRs preceded shorter latency pro-reaches but longer latency anti-reaches. Although converging evidence suggests that the SLR is relayed via a tectoreticulospinal pathway, our results show that task-related signals modulate visual signals feeding into this pathway. The SLR therefore provides a trial-by-trial window into how visual information is integrated with cognitive control in humans. SIGNIFICANCE STATEMENT: The presentation of a visual stimulus elicits a trial-by-trial stimulus-locked response (SLR) on the human limb within 100 ms. Here, we show that the SLR continues to reflect stimulus location even when subjects move in the opposite direction (an anti-reach). Remarkably, the attenuation of SLR magnitude reflected the cognitive control required to generate a correct anti-reach, with greater degrees of attenuation preceding shorter-latency anti-reaches and no attenuation preceding error trials. Our results are strikingly similar to neurophysiological recordings in the superior colliculus of nonhuman primates generating anti-saccades, implicating the tectoreticulospinal pathway. Measuring SLR magnitude therefore provides an unprecedented trial-by-trial opportunity to assess the influence of cognitive control on the initial processing of a visual stimulus in humans.


Assuntos
Retroalimentação Sensorial/fisiologia , Movimento/fisiologia , Músculo Esquelético/fisiologia , Tempo de Reação/fisiologia , Reflexo/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino , Músculo Esquelético/inervação , Estimulação Luminosa/métodos , Análise e Desempenho de Tarefas , Adulto Jovem
13.
J Am Chem Soc ; 139(32): 11008-11011, 2017 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-28742960

RESUMO

A porphyrin-edged metal-organic tetrahedron forms host-guest complexes containing 1-4 equiv of fullerene C60, depending on the solvent employed. The molecules of C60 were bound anticooperatively within well-defined pockets; an X-ray crystal structure of three fullerenes inside the tetrahedron was obtained. Electrochemical measurements revealed that the electron-accepting properties of the fullerenes inside the capsules were altered depending on the mode of encapsulation. The binding of multiple fullerenes was observed to increase the electron affinity of the overall cluster, providing a noncovalent method of tuning fullerene electronics.

15.
J Neurophysiol ; 116(2): 645-57, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27169506

RESUMO

When a saccade is expected to result in a reward, both neural activity in oculomotor areas and the saccade itself (e.g., its vigor and latency) are altered (compared with when no reward is expected). As such, it is unclear whether the correlations of neural activity with reward indicate a representation of reward beyond a movement representation; the modulated neural activity may simply represent the differences in motor output due to expected reward. Here, to distinguish between these possibilities, we trained monkeys to perform a natural scene search task while we recorded from the frontal eye field (FEF). Indeed, when reward was expected (i.e., saccades to the target), FEF neurons showed enhanced responses. Moreover, when monkeys accidentally made eye movements to the target, firing rates were lower than when they purposively moved to the target. Thus, neurons were modulated by expected reward rather than simply the presence of the target. We then fit a model that simultaneously included components related to expected reward and saccade parameters. While expected reward led to shorter latency and higher velocity saccades, these behavioral changes could not fully explain the increased FEF firing rates. Thus, FEF neurons appear to encode motivational factors such as reward expectation, above and beyond the kinematic and behavioral consequences of imminent reward.


Assuntos
Lobo Frontal/fisiologia , Neurônios/fisiologia , Recompensa , Movimentos Sacádicos/fisiologia , Campos Visuais/fisiologia , Potenciais de Ação/fisiologia , Animais , Feminino , Lobo Frontal/citologia , Modelos Lineares , Macaca mulatta , Tempo de Reação/fisiologia , Estatísticas não Paramétricas
16.
J Neurophysiol ; 116(3): 1328-43, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27250912

RESUMO

When we search for visual objects, the features of those objects bias our attention across the visual landscape (feature-based attention). The brain uses these top-down cues to select eye movement targets (spatial selection). The frontal eye field (FEF) is a prefrontal brain region implicated in selecting eye movements and is thought to reflect feature-based attention and spatial selection. Here, we study how FEF facilitates attention and selection in complex natural scenes. We ask whether FEF neurons facilitate feature-based attention by representing search-relevant visual features or whether they are primarily involved in selecting eye movement targets in space. We show that search-relevant visual features are weakly predictive of gaze in natural scenes and additionally have no significant influence on FEF activity. Instead, FEF activity appears to primarily correlate with the direction of the upcoming eye movement. Our result demonstrates a concrete need for better models of natural scene search and suggests that FEF activity during natural scene search is explained primarily by spatial selection.


Assuntos
Atenção/fisiologia , Movimentos Oculares/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Potenciais de Ação , Animais , Área Sob a Curva , Medições dos Movimentos Oculares , Feminino , Modelos Lineares , Macaca mulatta , Microeletrodos , Modelos Neurológicos , Atividade Motora/fisiologia , Testes Neuropsicológicos , Estimulação Luminosa , Curva ROC
17.
Bull Math Biol ; 78(10): 2057-2090, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27704329

RESUMO

Mechanistic mathematical models are increasingly used to evaluate the effectiveness of different interventions for HIV prevention and to inform public health decisions. By focusing exclusively on the impact of the interventions, the importance of the demographic processes in these studies is often underestimated. In this paper, we use simple deterministic models to assess the effectiveness of pre-exposure prophylaxis in reducing the HIV transmission and to explore the influence of the recruitment mechanisms on the epidemic and effectiveness projections. We employ three commonly used formulas that correspond to constant, proportional and logistic recruitment and compare the dynamical properties of the resulting models. Our analysis exposes substantial differences in the transient and asymptotic behavior of the models which result in 47 % variation in population size and more than 6 percentage points variation in HIV prevalence over 40 years between models using different recruitment mechanisms. We outline the strong influence of recruitment assumptions on the impact of HIV prevention interventions and conclude that detailed demographic data should be used to inform the integration of recruitment processes in the models before HIV prevention is considered.


Assuntos
Epidemias/prevenção & controle , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Simulação por Computador , Infecções por HIV/transmissão , Humanos , Conceitos Matemáticos , Modelos Biológicos , Dinâmica Populacional , Profilaxia Pré-Exposição , Prevalência , Saúde Pública , África do Sul/epidemiologia
18.
Chem Soc Rev ; 44(2): 419-32, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25029235

RESUMO

Over the last decade molecular containers have been increasingly studied within the context of complex chemical systems. Herein we discuss selected examples from the literature concerning three aspects of this field: complex host-guest behaviour, adaptive transformations of molecular containers and reactivity modulation within them.


Assuntos
Substâncias Macromoleculares/química , Antracenos/química , Catálise , Enzimas/química , Hidrólise , Cinética , Espectroscopia de Ressonância Magnética , Metais/química , Conformação Molecular , Piridinas/química , Termodinâmica
19.
Clin Infect Dis ; 61 Suppl 5: S578-85, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26553691

RESUMO

BACKGROUND: In 2010, mass vaccination with a then-new meningococcal A polysaccharide-tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction. METHODS: Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ≥0.1 IU/mL (indicating short-term protection) and ≥1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models. RESULTS: Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre-PsA-TT, significantly higher GMCs in all age-sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6-36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7-43.3; P < .0001) pre- and postvaccination. CONCLUSIONS: Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Antitoxina Tetânica/sangue , Toxoide Tetânico/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Mali , Adulto Jovem
20.
J Neurophysiol ; 114(2): 902-13, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26063777

RESUMO

Recent studies have described a phenomenon wherein the onset of a peripheral visual stimulus elicits short-latency (<100 ms) stimulus-locked recruitment (SLR) of neck muscles in nonhuman primates (NHPs), well before any saccadic gaze shift. The SLR is thought to arise from visual responses within the intermediate layers of the superior colliculus (SCi), hence neck muscle recordings may reflect presaccadic activity within the SCi, even in humans. We obtained bilateral intramuscular recordings from splenius capitis (SPL, an ipsilateral head-turning muscle) from 28 human subjects performing leftward or rightward visually guided eye-head gaze shifts. Evidence of an SLR was obtained in 16/55 (29%) of samples; we also observed examples where the SLR was present only unilaterally. We compared these human results with those recorded from a sample of eight NHPs from which recordings of both SPL and deeper suboccipital muscles were available. Using the same criteria, evidence of an SLR was obtained in 8/14 (57%) of SPL recordings, but in 26/29 (90%) of recordings from suboccipital muscles. Thus, both species-specific and muscle-specific factors contribute to the low SLR prevalence in human SPL. Regardless of the presence of the SLR, neck muscle activity in both human SPL and in NHPs became predictive of the reaction time of the ensuing saccade gaze shift ∼70 ms after target appearance; such pregaze recruitment likely reflects developing SCi activity, even if the tectoreticulospinal pathway does not reliably relay visually related activity to SPL in humans.


Assuntos
Antecipação Psicológica/fisiologia , Atividade Motora/fisiologia , Músculos do Pescoço/fisiologia , Movimentos Sacádicos/fisiologia , Adulto , Animais , Eletromiografia , Feminino , Humanos , Macaca fascicularis , Macaca mulatta , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Especificidade da Espécie
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