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Observers show biases in attention when viewing objects within versus outside of their hands' grasping space. While the hands' proximity to stimuli plays a key role in these effects, recent evidence suggests an observer's affordances for grasping actions also shape visual processing near the hands. The current study examined the relative contributions of proximity and affordances in introducing attentional biases in peripersonal space. Participants placed a single hand on a visual display and detected targets appearing near or far from the hand. Across conditions, the hand was either free, creating an affordance for a grasping action, or immobilized using an orthosis, interfering with the potential to grasp. Replicating previous findings, participants detected targets appearing near the hand more quickly than targets appearing far from the hand. Immobilizing the hands did not disrupt this effect, suggesting that proximity alone is sufficient to facilitate target detection in peripersonal space.
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Sesgo Atencional/fisiología , Inmovilización , Desempeño Psicomotor/fisiología , Atención/fisiología , Humanos , Restricción FísicaRESUMEN
Observers experience visual biases in the area around handheld tools. These biases may occur when active use leads an observer to incorporate a tool into the body schema. However, the visual salience of a handheld tool may instead create an attentional prioritization that is not reliant on body-based representations. We investigated these competing explanations of near-tool visual biases in two experiments during which participants performed a target detection task. Targets could appear near or far from a tool positioned next to a display. In Experiment 1, participants showed facilitation in detecting targets that appeared near a simple handheld rake tool regardless of whether they first used the rake to retrieve objects, but participants who only viewed the tool without holding it were no faster to detect targets appearing near the rake than targets that appeared on the opposite side of the display. In a second experiment, participants who held a novel magnetic tool again showed a near-tool bias even when they refrained from using the tool. Taken together, these results suggest active use is unnecessary, but visual salience is not sufficient, to introduce visual biases in peri-tool space.
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Atención , Imagen Corporal , Humanos , Sesgo , Cementos de Resina , Percepción EspacialRESUMEN
Parkinson's disease (PD) rodent models provide insight into the relationship between nigrostriatal dopamine (DA) signaling and locomotor function. Although toxin-based rat models produce frank nigrostriatal neuron loss and eventual motor decline characteristic of PD, the rapid nature of neuronal loss may not adequately translate premotor traits, such as cognitive decline. Unfortunately, rodent genetic PD models, like the Pink1 knockout (KO) rat, often fail to replicate the differential severity of striatal DA and tyrosine hydroxylase (TH) loss, and a bradykinetic phenotype, reminiscent of human PD. To elucidate this inconsistency, we evaluated aging as a progression factor in the timing of motor and non-motor cognitive impairments. Male PINK1 KO and age-matched wild type (WT) rats were evaluated in a longitudinal study from 3 to 16 months old in one cohort, and in a cross-sectional study of young adult (6-7 months) and aged (18-19 months) in another cohort. Young adult PINK1 KO rats exhibited hyperkinetic behavior associated with elevated DA and TH in the substantia nigra (SN), which decreased therein, but not striatum, in the aged KO rats. Additionally, norepinephrine levels decreased in aged KO rats in the prefrontal cortex (PFC), paired with a higher DA levels in young and aged KO. Although a younger age of onset characterizes familial forms of PD, our results underscore the critical need to consider age-related factors. Moreover, the results indicate that compensatory mechanisms may exist to preserve locomotor function, evidenced by increased DA in the SN early in the lifespan, in response to deficient PINK1 function, which declines with aging and the onset of motor decline.
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Envejecimiento , Cuerpo Estriado , Dopamina , Proteínas Quinasas , Sustancia Negra , Tirosina 3-Monooxigenasa , Animales , Tirosina 3-Monooxigenasa/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/deficiencia , Proteínas Quinasas/metabolismo , Sustancia Negra/metabolismo , Envejecimiento/genética , Masculino , Ratas , Dopamina/metabolismo , Cuerpo Estriado/metabolismo , Actividad Motora/fisiología , Actividad Motora/genética , Ratas TransgénicasRESUMEN
Parkinson's disease (PD) rodent models provide insight into the relationship between nigrostriatal dopamine (DA) signaling and locomotor function. Although toxin-based rat models produce frank nigrostriatal neuron loss and eventual motor decline characteristic of PD, the rapid nature of neuronal loss may not adequately translate premotor traits, such as cognitive decline. Unfortunately, rodent genetic PD models, like the Pink1 knockout (KO) rat, often fail to replicate the differential severity of striatal DA and tyrosine hydroxylase (TH) loss, and a bradykinetic phenotype, reminiscent of human PD. To elucidate this inconsistency, we evaluated aging as a progression factor in the timing of motor and non-motor cognitive impairments. Male PINK1 KO and age-matched wild type (WT) rats were evaluated in a longitudinal study from 3 to 16 months old in one cohort, and in a cross-sectional study of young adult (6-7 months) and aged (18-19 months) in another cohort. Young adult PINK1 KO rats exhibited hyperkinetic behavior associated with elevated DA and TH in the substantia nigra (SN), which decreased therein, but not striatum, in the aged KO rats. Additionally, norepinephrine levels decreased in aged KO rats in the prefrontal cortex (PFC), paired with a higher DA content in young and aged KO. Although a younger age of onset characterizes familial forms of PD, our results underscore the critical need to consider age-related factors. Moreover, the results indicate that compensatory mechanisms may exist to preserve locomotor function, evidenced by increased DA in the SN early in the lifespan, in response to deficient PINK1 function, which declines with aging and the onset of motor impairment.
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Alleviation of motor impairment by aerobic exercise (AE) in Parkinson's disease (PD) patients points to activation of neurobiological mechanisms that may be targetable by therapeutic approaches. However, evidence for AE-related recovery of striatal dopamine (DA) signaling or tyrosine hydroxylase (TH) loss has been inconsistent in rodent studies. This ambiguity may be related to the timing of AE intervention in relation to the status of nigrostriatal neuron loss. Here, we replicated human PD at diagnosis by establishing motor impairment with >80% striatal DA and TH loss prior to initiating AE, and assessed its potential to alleviate motor decline and restore DA and TH loss. We also evaluated if serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of human PD severity, changed in response to AE. 6-hydroxydopamine (6-OHDA) was infused unilaterally into rat medial forebrain bundle to induce progressive nigrostriatal neuron loss over 28 days. Moderate intensity AE (3× per week, 40 min/session), began 8-10 days post-lesion following establishment of impaired forelimb use. Striatal tissue DA, TH protein and mRNA, and serum levels of NfL/GFAP were determined 3-wks after AE began. Despite severe striatal DA depletion at AE initiation, forelimb use deficits and hypokinesia onset were alleviated by AE, without recovery of striatal DA or TH protein loss, but reduced NfL and GFAP serum levels. This proof-of-concept study shows AE alleviates motor impairment when initiated with >80% striatal DA loss without obligate recovery of striatal DA or TH protein. Moreover, the AE-related reduction of NfL and GFAP serum levels may serve as objective blood-based biomarkers of AE efficacy.
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Biomarcadores , Cuerpo Estriado , Dopamina , Oxidopamina , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa , Animales , Ratas , Tirosina 3-Monooxigenasa/metabolismo , Oxidopamina/toxicidad , Masculino , Cuerpo Estriado/metabolismo , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Biomarcadores/sangre , Dopamina/metabolismo , Dopamina/sangre , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína Ácida Fibrilar de la Glía/sangre , Índice de Severidad de la Enfermedad , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/metabolismo , Enfermedad de Parkinson/sangre , Terapia por Ejercicio/métodosRESUMEN
This paper highlights how immersive educational experiences can help students understand the United Nations' Sustainable Development Goals (SDGs) and their relation to leadership. The paper provides an example of how a carefully designed faculty-led program using original research can cultivate cross-cultural competencies and build student knowledge and skills to support sustainability. Educators can use this paper as a guide to other immersive experiences to address the SDGs while developing student leadership capacity.
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Aprendizaje Basado en Problemas , Desarrollo Sostenible , Humanos , Liderazgo , Aprendizaje , DocentesRESUMEN
Although glial cell line-derived neurotrophic factor (GDNF) showed efficacy in preclinical and early clinical studies to alleviate parkinsonian signs in Parkinson's disease (PD), later trials did not meet primary endpoints, giving pause to consider further investigation. While GDNF dose and delivery methods may have contributed to diminished efficacy, one crucial aspect of these clinical studies is that GDNF treatment across all studies began â¼8 years after PD diagnosis; a time point representing several years after near 100% depletion of nigrostriatal dopamine markers in striatum and at least 50% in substantia nigra (SN), and is later than the timing of GDNF treatment in preclinical studies. With nigrostriatal terminal loss exceeding 70% at PD diagnosis, we utilized hemi-parkinsonian rats to determine if expression of GDNF family receptor, GFR-α1, and receptor tyrosine kinase, RET, differed between striatum and SN at 1 and 4 weeks following a 6-hydroxydopamine (6-OHDA) lesion. Whereas GDNF expression changed minimally, GFR-α1 expression decreased progressively in striatum and in tyrosine hydroxylase positive (TH+) cells in SN, correlating with reduced TH cell number. However, in nigral astrocytes, GFR-α1 expression increased. RET expression decreased maximally in striatum by 1 week, whereas in the SN, a transient bilateral increase occurred that returned to control levels by 4 weeks. Expression of brain-derived neurotrophic factor (BDNF) or its receptor, TrkB, were unchanged throughout lesion progression. Together, these results reveal that differential GFR-α1 and RET expression between the striatum and SN, and cell-specific differences in GFR-α1 expression in SN, occur during nigrostriatal neuron loss. Targeting loss of GDNF receptors appears critical to enhance GDNF therapeutic efficacy against nigrostriatal neuron loss. Significance Statement: Although preclinical evidence supports that GDNF provides neuroprotection and improves locomotor function in preclinical studies, clinical data supporting its efficacy to alleviate motor impairment in Parkinson's disease patients remains uncertain. Using the established 6-OHDA hemi-parkinsonian rat model, we determined whether expression of its cognate receptors, GFR-α1 and RET, were differentially affected between striatum and substantia nigra in a timeline study. In striatum, there was early and significant loss of RET, but a gradual, progressive loss of GFR-α1. In contrast, RET transiently increased in lesioned substantia nigra, but GFR-α1 progressively decreased only in nigrostriatal neurons and correlated with TH cell loss. Our results indicate that direct availability of GFR-α1 may be a critical element that determines GDNF efficacy following striatal delivery. Highlights: GDNF expression was minimally affected by nigrostriatal lesionGDNF family receptor, GFR-α1, progressively decreased in striatum and in TH neurons in SN.GFR-α1 expression decreased along with TH neurons as lesion progressedGFR-α1 increased bilaterally in GFAP+ cells suggesting an inherent response to offset TH neuron lossRET expression was severely reduced in striatum, whereas it increased in SN early after lesion induction.
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Although glial cell line-derived neurotrophic factor (GDNF) showed efficacy in preclinical and early clinical studies to alleviate parkinsonian signs in Parkinson's disease (PD), later trials did not meet primary endpoints, giving pause to consider further investigation. While GDNF dose and delivery methods may have contributed to diminished efficacy, one crucial aspect of these clinical studies is that GDNF treatment began â¼8 years after PD diagnosis; a time point representing several years after near 100% depletion of nigrostriatal dopamine markers in striatum and at least 50% in substantia nigra (SN), which represents a time point of initiating GDNF treatment later than reported in some preclinical studies. With nigrostriatal terminal loss exceeding 70% at PD diagnosis, we utilized hemiparkinsonian rats to determine if expression of GDNF family receptor, GFR-α1, and receptor tyrosine kinase, RET, differed between striatum and SN at 1 and 4 weeks following a 6-hydroxydopamine (6-OHDA) hemilesion. Whereas GDNF expression changed minimally, GFR-α1 expression decreased progressively in striatum and in tyrosine hydroxylase positive (TH+) cells in SN, correlating with reduced TH cell number. However, in nigral astrocytes, GFR-α1 expression increased. RET expression decreased maximally in striatum by 1 week, whereas in the SN, a transient bilateral increase occurred, returning to control levels by 4 weeks. Expression of brain-derived neurotrophic factor (BDNF) or its receptor, TrkB, were unchanged throughout lesion progression. Together, these results reveal that differential GFR-α1 and RET expression between the striatum and SN, and cell-specific differences in GFR-α1 expression in SN, occur during nigrostriatal neuron loss. Targeting loss of GDNF receptors thus appears critical to enhance GDNF therapeutic efficacy against nigrostriatal neuron loss. SIGNIFICANCE STATEMENT: Although preclinical evidence supports that GDNF provides neuroprotection and improves locomotor function in preclinical studies, there is uncertainty if it can alleviate motor impairment in Parkinson's disease patients. Using the established 6-OHDA hemiparkinsonian rat model, we determined whether expression of its cognate receptors, GFR-α1 and RET, were differentially affected between striatum and substantia nigra in a timeline study. In striatum, there was early and significant loss of RET, but a gradual, progressive loss of GFR-α1. In contrast, RET transiently increased in lesioned substantia nigra, but GFR-α1 progressively decreased only in nigrostriatal neurons and correlated with TH cell loss. Our results indicate that direct availability of GFR-α1 may be a critical element that determines GDNF efficacy following striatal delivery.
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Enfermedad de Parkinson , Animales , Ratas , Cuerpo Estriado/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Oxidopamina/toxicidad , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Compensatory mechanisms that augment dopamine (DA) signaling are thought to mitigate onset of hypokinesia prior to major loss of tyrosine hydroxylase (TH) in striatum that occurs in Parkinson's disease. However, the identity of such mechanisms remains elusive. In the present study, the rat nigrostriatal pathway was unilaterally-lesioned with 6-hydroxydopamine (6-OHDA) to determine whether differences in DA content, TH protein, TH phosphorylation, or D1 receptor expression in striatum or substantia nigra (SN) aligned with hypokinesia onset and severity at two time points. In striatum, DA and TH loss reached its maximum (>90%) 7 days after lesion induction. However, in SN, no DA loss occurred, despite â¼60% TH loss. Hypokinesia was established at 21 days post-lesion and maintained at 28 days. At this time, DA loss was â¼60% in the SN, but still of lesser magnitude than TH loss. At day 7 and 28, ser31 TH phosphorylation increased only in SN, corresponding to less DA versus TH protein loss. In contrast, ser40 TH phosphorylation was unaffected in either region. Despite DA loss in both regions at day 28, D1 receptor expression increased only in lesioned SN. These results support the concept that augmented components of DA signaling in the SN, through increased ser31 TH phosphorylation and D1 receptor expression, contribute as compensatory mechanisms against progressive nigrostriatal neuron and TH protein loss, and may mitigate hypokinesia severity.
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Hipocinesia , Tirosina 3-Monooxigenasa , Animales , Ratas , Fosforilación , Dopamina , Neuronas , Oxidopamina/toxicidad , Sustancia NegraRESUMEN
Background: Alleviation of motor impairment by aerobic exercise (AE) in Parkinson's disease (PD) points to a CNS response that could be targeted by therapeutic approaches, but recovery of striatal dopamine (DA) or tyrosine hydroxylase (TH) has been inconsistent in rodent studies. Objective: To increase translation of AE, 3 components were implemented into AE design to determine if recovery of established motor impairment, concomitant with >80% striatal DA and TH loss, was possible. We also evaluated if serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), blood-based biomarkers of disease severity in human PD, were affected. Methods: We used a 6-OHDA hemiparkinson rat model featuring progressive nigrostriatal neuron loss over 28 days, with impaired forelimb use 7 days post-lesion, and hypokinesia onset 21 days post-lesion. After establishing forelimb use deficits, moderate intensity AE began 1-3 days later, 3x per week, for 40 min/session. Motor assessments were conducted weekly for 3 wks, followed by determination of striatal DA, TH protein and mRNA, and NfL and GFAP serum levels. Results: Seven days after 6-OHDA lesion, recovery of depolarization-stimulated extracellular DA and DA tissue content was <10%, representing severity of DA loss in human PD, concomitant with 50% reduction in forelimb use. Despite severe DA loss, recovery of forelimb use deficits and alleviation of hypokinesia progression began after 2 weeks of AE and was maintained. Increased NfLand GFAP levels from lesion were reduced by AE. Despite these AE-driven changes, striatal DA tissue and TH protein levels were unaffected. Conclusions: This proof-of-concept study shows AE, using exercise parameters within the capabilities most PD patients, promotes recovery of established motor deficits in a rodent PD model, concomitant with reduced levels of blood-based biomarkers associated with PD severity, without commensurate increase in striatal DA or TH protein.
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BACKGROUND: Residents in care homes have been severely impacted by COVID-19. We describe trends in the mortality risk among residents of care homes compared to private homes. METHODS: On behalf of NHS England we used OpenSAFELY-TPP to calculate monthly age-standardised risks of death due to all causes and COVID-19 among adults aged >=65 years between 1/2/2019 and 31/03/2021. Care home residents were identified using linkage to Care and Quality Commission data. FINDINGS: We included 4,340,648 people aged 65 years or older on the 1st of February 2019, 2.2% of whom were classified as residing in a care or nursing home. Age-standardised mortality risks were approximately 10 times higher among care home residents compared to those in private housing in February 2019: comparative mortality figure (CMF) = 10.59 (95%CI = 9.51, 11.81) among women, and 10.87 (9.93, 11.90) among men. By April 2020 these relative differences had increased to more than 17 times with CMFs of 17.57 (16.43, 18.79) among women and 18.17 (17.22, 19.17) among men. CMFs did not increase during the second wave, despite a rise in the absolute age-standardised COVID-19 mortality risks. INTERPRETATION: COVID-19 has had a disproportionate impact on the mortality of care home residents in England compared to older residents of private homes, but only in the first wave. This may be explained by a degree of acquired immunity, improved protective measures or changes in the underlying frailty of the populations. The care home population should be prioritised for measures aimed at controlling COVID-19. FUNDING: Medical Research Council MR/V015737/1.
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OBJECTIVE: To investigate whether risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outcomes of coronavirus disease 2019 (covid-19) differed between adults living with and without children during the first two waves of the UK pandemic. DESIGN: Population based cohort study, on behalf of NHS England. SETTING: Primary care data and pseudonymously linked hospital and intensive care admissions and death records from England, during wave 1 (1 February to 31 August 2020) and wave 2 (1 September to 18 December 2020). PARTICIPANTS: Two cohorts of adults (18 years and over) registered at a general practice on 1 February 2020 and 1 September 2020. MAIN OUTCOME MEASURES: Adjusted hazard ratios for SARS-CoV-2 infection, covid-19 related admission to hospital or intensive care, or death from covid-19, by presence of children in the household. RESULTS: Among 9 334 392adults aged 65 years and under, during wave 1, living with children was not associated with materially increased risks of recorded SARS-CoV-2 infection, covid-19 related hospital or intensive care admission, or death from covid-19. In wave 2, among adults aged 65 years and under, living with children of any age was associated with an increased risk of recorded SARS-CoV-2 infection (hazard ratio 1.06 (95% confidence interval 1.05 to 1.08) for living with children aged 0-11 years; 1.22 (1.20 to 1.24) for living with children aged 12-18 years) and covid-19 related hospital admission (1.18 (1.06 to 1.31) for living with children aged 0-11; 1.26 (1.12 to 1.40) for living with children aged 12-18). Living with children aged 0-11 was associated with reduced risk of death from both covid-19 and non-covid-19 causes in both waves; living with children of any age was also associated with lower risk of dying from non-covid-19 causes. For adults 65 years and under during wave 2, living with children aged 0-11 years was associated with an increased absolute risk of having SARS-CoV-2 infection recorded of 40-60 per 10 000 people, from 810 to between 850 and 870, and an increase in the number of hospital admissions of 1-5 per 10 000 people, from 160 to between 161 and 165. Living with children aged 12-18 years was associated with an increase of 160-190 per 10 000 in the number of SARS-CoV-2 infections and an increase of 2-6 per 10 000 in the number of hospital admissions. CONCLUSIONS: In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.
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COVID-19/epidemiología , Composición Familiar , Hospitalización/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adolescente , Adulto , Anciano , COVID-19/mortalidad , COVID-19/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Inglaterra/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Características de la Residencia , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Background: Care home residents have been severely affected by the COVID-19 pandemic. Electronic Health Records (EHR) hold significant potential for studying the healthcare needs of this vulnerable population; however, identifying care home residents in EHR is not straightforward. We describe and compare three different methods for identifying care home residents in the newly created OpenSAFELY-TPP data analytics platform. Methods: Working on behalf of NHS England, we identified individuals aged 65 years or older potentially living in a care home on the 1st of February 2020 using (1) a complex address linkage, in which cleaned GP registered addresses were matched to old age care home addresses using data from the Care and Quality Commission (CQC); (2) coded events in the EHR; (3) household identifiers, age and household size to identify households with more than 3 individuals aged 65 years or older as potential care home residents. Raw addresses were not available to the investigators. Results: Of 4,437,286 individuals aged 65 years or older, 2.27% were identified as potential care home residents using the complex address linkage, 1.96% using coded events, 3.13% using household size and age and 3.74% using either of these methods. 53,210 individuals (32.0% of all potential care home residents) were classified as care home residents using all three methods. Address linkage had the largest overlap with the other methods; 93.3% of individuals identified as care home residents using the address linkage were also identified as such using either coded events or household age and size. Conclusion: We have described the partial overlap between three methods for identifying care home residents in EHR, and provide detailed instructions for how to implement these in OpenSAFELY-TPP to support research into the impact of the COVID-19 pandemic on care home residents.
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Previous studies have shown that after actively using a handheld tool for a period of time, participants show visual biases toward stimuli presented near the end of the tool. Research suggests this is driven by an incorporation of the tool into the observer's body schema, extending peripersonal space to surround the tool. This study aims to investigate whether the same visual biases might be seen near remotely operated tools. Participants used tools-a handheld rake (Experiment 1), a remote-controlled drone (Experiment 2), a remote-controlled excavator (Experiment 3), or a handheld excavator (Experiment 4)-to rake sand for several minutes, then performed a target-detection task in which they made speeded responses to targets appearing near and far from the tool. In Experiment 1, participants detected targets appearing near the rake significantly faster than targets appearing far from the rake, replicating previous findings. We failed to find strong evidence of improved target detection near remotely operated tools in Experiments 2 and 3, but found clear evidence of near-tool facilitation in Experiment 4 when participants physically picked up the excavator and used it as a handheld tool. These results suggest that observers may not incorporate remotely operated tools into the body schema in the same manner as handheld tools. We discuss potential mechanisms that may drive these differences in embodiment between handheld and remote-controlled tools.
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Espacio Personal , Desempeño Psicomotor , Imagen Corporal , Humanos , Percepción EspacialRESUMEN
Physiological limitations on the visual system require gaze to move from location to location to extract the most relevant information within a scene. Therefore, gaze provides a real-time index of the information-processing priorities of the visual system. We investigated gaze allocation during mind wandering (MW), a state where cognitive priorities shift from processing task-relevant external stimuli (i.e., the visual world) to task-irrelevant internal thoughts. In both a main study and a replication, we recorded the eye movements of college-aged adults who studied images of urban scenes and responded to pseudorandom thought probes on whether they were mind wandering or attentively viewing at the time of the probe. Probe-caught MW was associated with fewer and longer fixations, greater fixation dispersion, and more frequent eyeblinks (only observed in the main study) relative to periods of attentive scene viewing. These findings demonstrate that gaze indices typically considered to represent greater engagement with scene processing (e.g., longer fixations) can also indicate MW. In this way, the current work exhibits a need for empirical investigations and computational models of gaze control to account for MW for a more accurate representation of the moment-to-moment information-processing priorities of the visual system. (PsycINFO Database Record
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Atención/fisiología , Cognición/fisiología , Movimientos Oculares/fisiología , Percepción Visual/fisiología , Adolescente , Femenino , Humanos , Masculino , Estimulación Luminosa , Adulto JovenRESUMEN
OBJECTIVE: To identify clinical signs associated with and outcome of human exposure to Micotil 300 (tilmicosin injection). DESIGN: Retrospective case series. STUDY POPULATION: Reports of 3,168 human exposures to Micotil 300. PROCEDURES: Reports of human exposure to Micotil 300 submitted to the Elanco Animal Health Pharmacovigilance Unit between March 1992 and March 2005 were reviewed. RESULTS: At least 1 clinical sign was described in 1,404 (44%) reports, whereas the remaining 1,764 (56%) exposures were presumably asymptomatic. Eighty percent of exposures involved males; mean age was 38 years. Sixty-one percent of exposures were a result of accidental injection, with injection site pain, bleeding, swelling, or inflammation being the most common signs, followed by nausea, tachycardia, dizziness, anxiety, an abnormal taste, headache, lightheadedness, limb pain, paresthesia, chest pain, and soreness. Only 156 (5%) reports involved serious adverse effects (ie, tachycardia, bradycardia, hypertension, hypotension, heart disorder, chest pain, tachypnea, or death). There were reports of 13 deaths following tilmicosin exposure, but only 2 of those deaths were related to accidental exposure. Time to onset of clinical signs was < or = 60 minutes in 63 of the 156 (40%) reports involving serious adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the overall risk of accidental human exposure to tilmicosin resulting in serious adverse effects is low (approx 2 people for every 1 million doses administered). Nevertheless, safe handling and proper use should be emphasized.