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1.
PLoS One ; 18(5): e0285423, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37155632

RESUMEN

One of the primary jobs of visual perception is to build a three-dimensional representation of the world around us from our flat retinal images. These are a rich source of depth cues but no single one of them can tell us about scale (i.e., absolute depth and size). For example, the pictorial depth cues in a (perfect) scale model are identical to those in the real scene that is being modelled. Here we investigate image blur gradients, which derive naturally from the limited depth of field available for any optical device and can be used to help estimate visual scale. By manipulating image blur artificially to produce what is sometimes called fake tilt shift miniaturization, we provide the first performance-based evidence that human vision uses this cue when making forced-choice judgements about scale (identifying which of an image pair was a photograph of a full-scale railway scene, and which was a 1:76 scale model). The orientation of the blur gradient (relative to the ground plane) proves to be crucial, though its rate of change is less important for our task, suggesting a fairly coarse visual analysis of this image parameter.


Asunto(s)
Percepción de Profundidad , Percepción Visual , Humanos , Señales (Psicología) , Gravitación , Juicio
2.
Nat Commun ; 14(1): 1455, 2023 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-36927839

RESUMEN

Identifying how small molecules act to kill malaria parasites can lead to new "chemically validated" targets. By pressuring Plasmodium falciparum asexual blood stage parasites with three novel structurally-unrelated antimalarial compounds (MMV665924, MMV019719 and MMV897615), and performing whole-genome sequence analysis on resistant parasite lines, we identify multiple mutations in the P. falciparum acyl-CoA synthetase (ACS) genes PfACS10 (PF3D7_0525100, M300I, A268D/V, F427L) and PfACS11 (PF3D7_1238800, F387V, D648Y, and E668K). Allelic replacement and thermal proteome profiling validates PfACS10 as a target of these compounds. We demonstrate that this protein is essential for parasite growth by conditional knockdown and observe increased compound susceptibility upon reduced expression. Inhibition of PfACS10 leads to a reduction in triacylglycerols and a buildup of its lipid precursors, providing key insights into its function. Analysis of the PfACS11 gene and its mutations point to a role in mediating resistance via decreased protein stability.


Asunto(s)
Antimaláricos , Malaria Falciparum , Humanos , Plasmodium falciparum/metabolismo , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Mutación , Ligasas/metabolismo
3.
J Acoust Soc Am ; 151(5): 3369, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35649936

RESUMEN

Lexical bias is the tendency to perceive an ambiguous speech sound as a phoneme completing a word; more ambiguity typically causes greater reliance on lexical knowledge. A speech sound ambiguous between /g/ and /k/ is more likely to be perceived as /g/ before /ɪft/ and as /k/ before /ɪs/. The magnitude of this difference-the Ganong shift-increases when high cognitive load limits available processing resources. The effects of stimulus naturalness and informational masking on Ganong shifts and reaction times were explored. Tokens between /gɪ/ and /kɪ/ were generated using morphing software, from which two continua were created ("giss"-"kiss" and "gift"-"kift"). In experiment 1, Ganong shifts were considerably larger for sine- than noise-vocoded versions of these continua, presumably because the spectral sparsity and unnatural timbre of the former increased cognitive load. In experiment 2, noise-vocoded stimuli were presented alone or accompanied by contralateral interferers with constant within-band amplitude envelope, or within-band envelope variation that was the same or different across bands. The latter, with its implied spectro-temporal variation, was predicted to cause the greatest cognitive load. Reaction-time measures matched this prediction; Ganong shifts showed some evidence of greater lexical bias for frequency-varying interferers, but were influenced by context effects and diminished over time.


Asunto(s)
Percepción del Habla , Sesgo , Ruido/efectos adversos , Fonética , Tiempo de Reacción
4.
PLoS One ; 17(5): e0267056, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35511914

RESUMEN

Image processing algorithms are used to improve digital image representations in either their appearance or storage efficiency. The merit of these algorithms depends, in part, on visual perception by human observers. However, in practice, most are assessed numerically, and the perceptual metrics that do exist are criterion sensitive with several shortcomings. Here we propose an objective performance-based perceptual measure of image quality and demonstrate this by comparing the efficacy of a denoising algorithm for a variety of filters. For baseline, we measured detection thresholds for a white noise signal added to one of a pair of natural images in a two-alternative forced-choice (2AFC) paradigm where each image was selected randomly from a set of n = 308 on each trial. In a series of experimental conditions, the stimulus image pairs were passed through various configurations of a denoising algorithm. The differences in noise detection thresholds with and without denoising are objective perceptual measures of the ability of the algorithm to render noise invisible. This was a factor of two (6dB) in our experiment and consistent across a range of filter bandwidths and types. We also found that thresholds in all conditions converged on a common value of PSNR, offering support for this metric. We discuss how the 2AFC approach might be used for other algorithms including compression, deblurring and edge-detection. Finally, we provide a derivation for our Cartesian-separable log-Gabor filters, with polar parameters. For the biological vision community this has some advantages over the more typical (i) polar-separable variety and (ii) Cartesian-separable variety with Cartesian parameters.


Asunto(s)
Compresión de Datos , Procesamiento de Imagen Asistido por Computador , Algoritmos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Ruido , Relación Señal-Ruido
5.
Cell Chem Biol ; 29(2): 191-201.e8, 2022 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-34348113

RESUMEN

We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds. Genome editing confirms that mutations in PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate that PfAcAS is essential for asexual growth, and partial knockdown induces hypersensitivity to both compounds. In vitro biochemical assays using recombinantly expressed PfAcAS validates that MMV019721 and MMV084978 directly inhibit the enzyme by preventing CoA and acetate binding, respectively. Immunolocalization studies reveal that PfAcAS is primarily localized to the nucleus. Functional studies demonstrate inhibition of histone acetylation in compound-treated wild-type, but not in resistant parasites. Our findings identify and validate PfAcAS as an essential, druggable target involved in the epigenetic regulation of gene expression.


Asunto(s)
Acetato CoA Ligasa/antagonistas & inhibidores , Antimaláricos/farmacología , Inhibidores Enzimáticos/farmacología , Malaria/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Acetato CoA Ligasa/metabolismo , Antimaláricos/química , Inhibidores Enzimáticos/química , Humanos , Malaria/metabolismo , Modelos Moleculares , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/enzimología
6.
J Card Fail ; 28(1): 44-55, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34352394

RESUMEN

BACKGROUND: Heart failure (HF) causes high morbidity and mortality despite advances in medical therapy. Remote patient monitoring for HF allows for the optimization of medical therapy and prevention of HF hospitalizations. This study is the first to assess pulmonary artery diastolic pressures (PADP) using the CardioMEMS HF System (CMEMS) and cardiac implantable electronic device-based multisensor indexes (HeartLogic index [HLI]) using the HeartLogic HF Diagnostic (HL) in a small, retrospective cohort of patients with HF at a single center. METHODS AND RESULTS: Any hospitalization, HF hospitalization, HF-related outpatient visit, and pulmonary artery pressure action were recorded in 7 patients with concurrent CMEMS and HL measurements for at least 1 year. The median time before both platforms were implanted and present in the same participant was 3.12 months. The median study period was 1.44 years per participant. Data availability for HL was significantly higher at 99.6% compared with 64.1% adherence for CMEMS (P = .016). Overall, PADP was only weakly correlated to HLI (r = 0.098), but there was a 2.87 mm Hg (P = .014) estimated increase in PADP during HLI alert periods versus nonalert periods. Similarly, the estimated odds of being above a PADP goal was 4.7 times higher (95% confidence interval 3.0-7.2, P < .001) in HLI alert vs nonalert periods. CONCLUSIONS: Concurrent analysis of patients with CMEMS and HL showed an association between PADP and HLI, but the correlation was weak. However, there was a significant increase in PADP during HLI alert periods versus nonalert periods.


Asunto(s)
Insuficiencia Cardíaca , Estudios de Cohortes , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Hospitalización , Humanos , Monitoreo Fisiológico , Estudios Retrospectivos
7.
J Acoust Soc Am ; 150(5): 3693, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34852626

RESUMEN

Speech-on-speech informational masking arises because the interferer disrupts target processing (e.g., capacity limitations) or corrupts it (e.g., intrusions into the target percept); the latter should produce predictable errors. Listeners identified the consonant in monaural buzz-excited three-formant analogues of approximant-vowel syllables, forming a place of articulation series (/w/-/l/-/j/). There were two 11-member series; the vowel was either high-front or low-back. Series members shared formant-amplitude contours, fundamental frequency, and F1+F3 frequency contours; they were distinguished solely by the F2 frequency contour before the steady portion. Targets were always presented in the left ear. For each series, F2 frequency and amplitude contours were also used to generate interferers with altered source properties-sine-wave analogues of F2 (sine bleats) matched to their buzz-excited counterparts. Accompanying each series member with a fixed mismatched sine bleat in the contralateral ear produced systematic and predictable effects on category judgments; these effects were usually largest for bleats involving the fastest rate or greatest extent of frequency change. Judgments of isolated sine bleats using the three place labels were often unsystematic or arbitrary. These results indicate that informational masking by interferers involved corruption of target processing as a result of mandatory dichotic integration of F2 information, despite the grouping cues disfavoring this integration.


Asunto(s)
Inteligibilidad del Habla , Percepción del Habla , Estimulación Acústica , Juicio , Fonética , Acústica del Lenguaje
8.
J Acoust Soc Am ; 149(6): 3769, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34241493

RESUMEN

Three experiments explored the effects of abrupt changes in stimulus properties on streaming dynamics. Listeners monitored 20-s-long low- and high-frequency (LHL-) tone sequences and reported the number of streams heard throughout. Experiments 1 and 2 used pure tones and examined the effects of changing triplet base frequency and level, respectively. Abrupt changes in base frequency (±3-12 semitones) caused significant magnitude-related falls in segregation (resetting), regardless of transition direction, but an asymmetry occurred for changes in level (±12 dB). Rising-level transitions usually decreased segregation significantly, whereas falling-level transitions had little or no effect. Experiment 3 used pure tones (unmodulated) and narrowly spaced (±25 Hz) tone pairs (dyads); the two evoke similar excitation patterns, but dyads are strongly modulated with a distinctive timbre. Dyad-only sequences induced a strongly segregated percept, limiting scope for further build-up. Alternation between groups of pure tones and dyads produced large, asymmetric changes in streaming. Dyad-to-pure transitions caused substantial resetting, but pure-to-dyad transitions sometimes elicited even greater segregation than for the corresponding interval in dyad-only sequences (overshoot). The results indicate that abrupt changes in timbre can strongly affect the likelihood of stream segregation without introducing significant peripheral-channeling cues. These asymmetric effects of transition direction are reminiscent of subtractive adaptation in vision.


Asunto(s)
Percepción Auditiva , Audición , Estimulación Acústica , Adaptación Fisiológica , Señales (Psicología) , Factores de Tiempo
9.
Eur J Med Chem ; 215: 113227, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33601312

RESUMEN

Due to the surge in resistance to common therapies, malaria remains a significant concern to human health worldwide. In chloroquine (CQ)-resistant (CQ-R) strains of Plasmodium falciparum, CQ and related drugs are effluxed from the parasite's digestive vacuole (DV). This process is mediated by mutant isoforms of a protein called CQ resistance transporter (PfCRT). CQ-R strains can be partially re-sensitized to CQ by verapamil (VP), primaquine (PQ) and other compounds, and this has been shown to be due to the ability of these molecules to inhibit drug transport via PfCRT. We have previously developed a series of clotrimazole (CLT)-based antimalarial agents that possess inhibitory activity against PfCRT (4a,b). In our endeavor to develop novel PfCRT inhibitors, and to perform a structure-activity relationship analysis, we synthesized a new library of analogues. When the benzhydryl system was linked to a 4-aminoquinoline group (5a-f) the resulting compounds exhibited good cytotoxicity against both CQ-R and CQ-S strains of P. falciparum. The most potent inhibitory activity against the PfCRT-mediated transport of CQ was obtained with compound 5k. When compared to the reference compound, benzhydryl analogues of PQ (5i,j) showed a similar activity against blood-stage parasites, and a stronger in vitro potency against liver-stage parasites. Unfortunately, in the in vivo transmission blocking assays, 5i,j were inactive against gametocytes.


Asunto(s)
Antimaláricos/farmacología , Compuestos de Bencidrilo/farmacología , Plasmodium falciparum/efectos de los fármacos , Proteínas Protozoarias/antagonistas & inhibidores , Animales , Anopheles , Antimaláricos/síntesis química , Compuestos de Bencidrilo/síntesis química , Cloroquina/farmacología , Diseño de Fármacos , Farmacorresistencia Microbiana/efectos de los fármacos , Femenino , Células Hep G2 , Humanos , Proteínas de Transporte de Membrana , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Células 3T3 NIH , Pruebas de Sensibilidad Parasitaria , Isoformas de Proteínas/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/farmacología , Relación Estructura-Actividad , Xenopus
10.
IDCases ; 23: e01027, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33425680

RESUMEN

In the United States, C. gattii is considered to be endemic to the Pacific Northwest and although uncommon, additional cases have been documented in other regions including the Southeastern United States. While it has been hypothesized in the past that C. gattii may be endemic to the Southeastern United States, there remains a paucity of evidence. Here, we present a patient with no history of HIV/AIDS and no organ transplant and document the course of his disease and presentation. There were no adverse long-term neurological outcomes in this patient and the combination of steroid use, antifungal agents, and cerebrospinal fluid drainage resulted in his discharge from the hospital after 12 days. This patient's subacute presentation with vague neurological symptoms highlights the importance of understanding the treatment of rare causes of meningitis.

11.
Case Rep Infect Dis ; 2020: 2842315, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33294237

RESUMEN

Pasteurella multocida is a pathogen well known for its zoonotic transmission, most commonly by cats and dogs. When bacteremia ensures from an infection, patients with foreign objects present in their bodies, including prosthetic joints and mesh implants, become vulnerable to seeding. There have been multiple documented cases in which P. multocida bacteremia has resulted in infection of both native and prosthetic joints. Furthermore, cases have been documented in which patients with P. multocida bacteremia have developed meningitis and neurological complications. Here, we present a patient with multiple comorbidities including multifactorial immunocompromise, advanced age, and multiple prosthetic joints who developed prosthetic joint infection and spinal osteomyelitis after the development of Pasteurella bacteremia. Aggressive treatment was undertaken given her risk factors, and a combination of antibiotics and surgery was utilized, with the patient making a full recovery.

12.
J Acoust Soc Am ; 148(4): 2416, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33138537

RESUMEN

The impact of an extraneous formant on intelligibility is affected by the extent (depth) of variation in its formant-frequency contour. Two experiments explored whether this impact also depends on masker spectro-temporal coherence, using a method ensuring that interference occurred only through informational masking. Targets were monaural three-formant analogues (F1+F2+F3) of natural sentences presented alone or accompanied by a contralateral competitor for F2 (F2C) that listeners must reject to optimize recognition. The standard F2C was created using the inverted F2 frequency contour and constant amplitude. Variants were derived by dividing F2C into abutting segments (100-200 ms, 10-ms rise/fall). Segments were presented either in the correct order (coherent) or in random order (incoherent), introducing abrupt discontinuities into the F2C frequency contour. F2C depth was also manipulated (0%, 50%, or 100%) prior to segmentation, and the frequency contour of each segment either remained time-varying or was set to constant at the geometric mean frequency of that segment. The extent to which F2C lowered keyword scores depended on segment type (frequency-varying vs constant) and depth, but not segment order. This outcome indicates that the impact on intelligibility depends critically on the overall amount of frequency variation in the competitor, but not its spectro-temporal coherence.


Asunto(s)
Enmascaramiento Perceptual , Inteligibilidad del Habla , Percepción del Habla , Humanos , Reconocimiento en Psicología
13.
PLoS Comput Biol ; 16(9): e1008243, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32991585

RESUMEN

Understanding evolution requires detailed knowledge of genotype-phenotype maps; however, it can be a herculean task to measure every phenotype in a combinatorial map. We have developed a computational strategy to predict the missing phenotypes from an incomplete, combinatorial genotype-phenotype map. As a test case, we used an incomplete genotype-phenotype dataset previously generated for the malaria parasite's 'chloroquine resistance transporter' (PfCRT). Wild-type PfCRT (PfCRT3D7) lacks significant chloroquine (CQ) transport activity, but the introduction of the eight mutations present in the 'Dd2' isoform of PfCRT (PfCRTDd2) enables the protein to transport CQ away from its site of antimalarial action. This gain of a transport function imparts CQ resistance to the parasite. A combinatorial map between PfCRT3D7 and PfCRTDd2 consists of 256 genotypes, of which only 52 have had their CQ transport activities measured through expression in the Xenopus laevis oocyte. We trained a statistical model with these 52 measurements to infer the CQ transport activity for the remaining 204 combinatorial genotypes between PfCRT3D7 and PfCRTDd2. Our best-performing model incorporated a binary classifier, a nonlinear scale, and additive effects for each mutation. The addition of specific pairwise- and high-order-epistatic coefficients decreased the predictive power of the model. We evaluated our predictions by experimentally measuring the CQ transport activities of 24 additional PfCRT genotypes. The R2 value between our predicted and newly-measured phenotypes was 0.90. We then used the model to probe the accessibility of evolutionary trajectories through the map. Approximately 1% of the possible trajectories between PfCRT3D7 and PfCRTDd2 are accessible; however, none of the trajectories entailed eight successive increases in CQ transport activity. These results demonstrate that phenotypes can be inferred with known uncertainty from a partial genotype-phenotype dataset. We also validated our approach against a collection of previously published genotype-phenotype maps. The model therefore appears general and should be applicable to a large number of genotype-phenotype maps.


Asunto(s)
Genotipo , Fenotipo , Animales , Modelos Biológicos , Mutación , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Incertidumbre
14.
Nat Commun ; 11(1): 3922, 2020 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-32764664

RESUMEN

The Plasmodium falciparum chloroquine resistance transporter (PfCRT) is a key contributor to multidrug resistance and is also essential for the survival of the malaria parasite, yet its natural function remains unresolved. We identify host-derived peptides of 4-11 residues, varying in both charge and composition, as the substrates of PfCRT in vitro and in situ, and show that PfCRT does not mediate the non-specific transport of other metabolites and/or ions. We find that drug-resistance-conferring mutations reduce both the peptide transport capacity and substrate range of PfCRT, explaining the impaired fitness of drug-resistant parasites. Our results indicate that PfCRT transports peptides from the lumen of the parasite's digestive vacuole to the cytosol, thereby providing a source of amino acids for parasite metabolism and preventing osmotic stress of this organelle. The resolution of PfCRT's native substrates will aid the development of drugs that target PfCRT and/or restore the efficacy of existing antimalarials.


Asunto(s)
Antimaláricos/farmacología , Cloroquina/farmacología , Proteínas de Transporte de Membrana/metabolismo , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/metabolismo , Animales , Transporte Biológico Activo , Resistencia a Medicamentos/genética , Femenino , Interacciones Huésped-Parásitos/genética , Interacciones Huésped-Parásitos/fisiología , Humanos , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/metabolismo , Malaria Falciparum/parasitología , Proteínas de Transporte de Membrana/genética , Modelos Biológicos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Oligopéptidos/metabolismo , Oocitos/metabolismo , Plasmodium falciparum/genética , Transporte de Proteínas , Proteínas Protozoarias/genética , Xenopus laevis
15.
J Acoust Soc Am ; 147(2): 1113, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32113320

RESUMEN

Masking experienced when target speech is accompanied by a single interfering voice is often primarily informational masking (IM). IM is generally greater when the interferer is intelligible than when it is not (e.g., speech from an unfamiliar language), but the relative contributions of acoustic-phonetic and linguistic interference are often difficult to assess owing to acoustic differences between interferers (e.g., different talkers). Three-formant analogues (F1+F2+F3) of natural sentences were used as targets and interferers. Targets were presented monaurally either alone or accompanied contralaterally by interferers from another sentence (F0 = 4 semitones higher); a target-to-masker ratio (TMR) between ears of 0, 6, or 12 dB was used. Interferers were either intelligible or rendered unintelligible by delaying F2 and advancing F3 by 150 ms relative to F1, a manipulation designed to minimize spectro-temporal differences between corresponding interferers. Target-sentence intelligibility (keywords correct) was 67% when presented alone, but fell considerably when an unintelligible interferer was present (49%) and significantly further when the interferer was intelligible (41%). Changes in TMR produced neither a significant main effect nor an interaction with interferer type. Interference with acoustic-phonetic processing of the target can explain much of the impact on intelligibility, but linguistic factors-particularly interferer intrusions-also make an important contribution to IM.

16.
J Biomed Opt ; 25(1): 1-11, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31849205

RESUMEN

Hemozoin, the heme detoxification end product in malaria parasites during their growth in the red blood cells (RBCs), serves as an important marker for diagnosis and treatment target of malaria disease. However, the current method for hemozoin-targeted drug screening mainly relies on in vitro ß-hematin inhibition assays, which may lead to false-positive events due to under-representation of the real hemozoin crystal. Quantitative in situ imaging of hemozoin is highly desired for high-throughput screening of antimalarial drugs and for elucidating the mechanisms of antimalarial drugs. We present transient absorption (TA) imaging as a high-speed single-cell analysis platform with chemical selectivity to hemozoin. We first demonstrated that TA microscopy is able to identify ß-hematin, the artificial form of hemozoin, from the RBCs. We further utilized time-resolved TA imaging to in situ discern hemozoin from malaria-infected RBCs with optimized imaging conditions. Finally, we quantitatively analyzed the hemozoin amount in RBCs at different infection stages by single-shot TA imaging. These results highlight the potential of TA imaging for efficient antimalarial drug screening and drug mechanism investigation.


Asunto(s)
Eritrocitos/metabolismo , Hemoproteínas/metabolismo , Microscopía/métodos , Animales , Antimaláricos/farmacología , Cristalización , Evaluación Preclínica de Medicamentos , Eritrocitos/parasitología , Hemoproteínas/análisis , Hemoproteínas/química , Ensayos Analíticos de Alto Rendimiento , Humanos , Malaria Falciparum/sangre , Malaria Falciparum/parasitología , Microscopía Electrónica de Rastreo , Fenómenos Ópticos , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/metabolismo , Análisis de la Célula Individual/métodos
17.
J Acoust Soc Am ; 145(3): 1230, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-31067923

RESUMEN

Differences in ear of presentation and level do not prevent effective integration of concurrent speech cues such as formant frequencies. For example, presenting the higher formants of a consonant-vowel syllable in the opposite ear to the first formant protects them from upward spread of masking, allowing them to remain effective speech cues even after substantial attenuation. This study used three-formant (F1+F2+F3) analogues of natural sentences and extended the approach to include competitive conditions. Target formants were presented dichotically (F1+F3; F2), either alone or accompanied by an extraneous competitor for F2 (i.e., F1±F2C+F3; F2) that listeners must reject to optimize recognition. F2C was created by inverting the F2 frequency contour and using the F2 amplitude contour without attenuation. In experiment 1, F2C was always absent and intelligibility was unaffected until F2 attenuation exceeded 30 dB; F2 still provided useful information at 48-dB attenuation. In experiment 2, attenuating F2 by 24 dB caused considerable loss of intelligibility when F2C was present, but had no effect in its absence. Factors likely to contribute to this interaction include informational masking from F2C acting to swamp the acoustic-phonetic information carried by F2, and interaural inhibition from F2C acting to reduce the effective level of F2.

18.
J Occup Environ Med ; 61(2): e61-e64, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30531374

RESUMEN

OBJECTIVE: To compare implementation of robbery prevention strategies between gas station/convenience stores with liquor stores/grocery stores/pharmacies, restaurants/bars, and other retail businesses. METHODS: One hundred forty-nine retail businesses were evaluated by police personnel across four police departments for adherence to robbery prevention strategies. Assessment of these strategies occurred between November 2012 and October 2014. Implementation of these strategies were compared across business types using logistic regression. RESULTS: Liquor/grocery stores/pharmacies and restaurants/bars were less likely to have a high site assessment score for robbery prevention elements when compared with gas station/convenience stores. CONCLUSIONS: Non-gas station/convenience stores require stronger consideration when developing robbery prevention programs and policies to assure appropriate implementation of robbery prevention strategies.


Asunto(s)
Comercio/métodos , Robo/prevención & control , Entorno Construido , Comercio/organización & administración , Humanos , Estados Unidos , Grabación en Video
19.
Pan Afr Med J ; 29: 224, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30100978

RESUMEN

INTRODUCTION: in November, 2005, the South African (SA) National Department of Health (NDoH) mandated that, as from the 1st December, 2005, all new clinical trials to be conducted in the country must be registered on the South African National Clinical Trials Register (SANCTR). The objective was to compare access to the information contained in and the usability of the SANCTR with five other international on-line clinical trials registers. METHODS: Access to SANCTR was determined through the use of three search engines using the keywords "South African Clinical Trials." Five high-profile international registers were identified and accessed for comparative purposes. Each register was investigated for information on trials conducted in South Africa using a standardised data extraction form which listed 24 data items. The usability of the various on-line registers was determined through a self-administered questionnaire adapted from the five key usability factors previously defined in literature. Heuristic evaluation was carried out with 10 'experts' (Pharmacy staff and postgraduate students at Sefako Makgatho Health Sciences University (SMU)). Data generated from the heuristic evaluation were analysed using descriptive statistics, univariate and multivariate analyses. RESULTS: The SANCTR website had the highest ranking for access amongst the registers in all three selected search-engines after an internet search using the keywords "South African Clinical Trials". The total number of clinical trials registered varied among the registers. The WHO's International Clinical Trials Registry Platform (ICTRP) recorded 2 599 trials carried out in South Africa, with 2 260 registered in the ClinicalTrials.gov register, 2 196 in the SANCTR and 978, 149 and 174 in the European Union (EU), International Standard Randomised Controlled Trial Number (ISRCTN) and Pan African Clinical Trials (PACTR) registers respectively. The websites ClinicalTrials.gov and ISRCTN provided greater overall information per clinical trial registered and provided information on all 24 clinical trials data items. The PACTR had information on 23 of the 24 data items. The WHO and EU registers each contained 19 data items. The SANCTR provided the least information, only 11 data items. The heuristic evaluation identified ClinicalTrials.gov as the 'best' site, while the PACTR had the lowest rating for layout and design. The EU register and SANCTR were the least easily navigable. The respondents had the least satisfaction while using the 'Search' option in the SANCTR. Users also reported the SANCTR and the PACTR had the lowest overall user-friendliness. CONCLUSION: The fact that the SANCTR contains less information on SA clinical trials than other registers and is the least user-friendly warrants utmost attention. The study puts forward a case to the regulatory authority (currently the Medicines Control Council) as it takes on a new structure and working arrangements as the South African Health Products Regulatory Authority to optimise the SANCTR to be more user-friendly and contain more complete information on clinical trials conducted in SA.


Asunto(s)
Acceso a la Información , Ensayos Clínicos como Asunto , Sistema de Registros/normas , Humanos , Sudáfrica , Encuestas y Cuestionarios
20.
Hosp Pract (1995) ; 46(4): 221-228, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30092683

RESUMEN

BACKGROUND AND AIMS: Under-reporting of adverse drug reactions (ADRs) by health-care professionals (HCPs) is a worldwide problem. Spontaneous reporting in hospitals is scarce and several obstacles have been identified for this. Improved hospital-based reports could make important contributions to future care. Consequently, the objective of this study was to develop, implement and evaluate a structured pharmacist-driven pharmacovigilance (PV) system for in-patient ADR reporting in a leading public hospital in South Africa for future use in South Africa and wider. METHOD: Descriptive, operational intervention study with a pre-post design. Pharmacist-driven interventions targeted at ADR reporting were implemented. Convenience sampling was used to recruit HCPs [medical practitioners, pharmacists, pharmacist assistants, and nurses] to complete a self-administered questionnaire. The principal outcome measures were the number of the ADRs reported for inpatients, 18 months prior to and 18 months during the intervention period, as well as an evaluation of the intervention program in terms of continuous information and training. RESULTS: There was a significant increase in the number of HCPs reporting an ADR post-intervention (33.8% up from 12.1%; p < 0.0001). Reasons for non-reporting decreased significantly, e.g. 'How, where and when to report' an ADR (p = 0.0027) and 'Concern that the report may be wrong' (p = 0.0041). HCPs' knowledge of the ADR reporting system also improved appreciably. This was apart from pharmacists who were already knowledgeable. CONCLUSION: The results showed the benefits of pharmacist-driven interventions on HCPs' knowledge and awareness of PV and the number of the ADRs reported. Hospital management and policy makers should consider the important role pharmacists can play in improving rational and safe use of medicines among inpatients, based on appropriate training of HCPs and proper systems. As a result, help achieve the standards established by the Department of Health in South Africa.


Asunto(s)
Actitud del Personal de Salud , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Farmacéuticos/estadística & datos numéricos , Farmacovigilancia , Servicio de Farmacia en Hospital/organización & administración , Femenino , Personal de Salud/estadística & datos numéricos , Humanos , Masculino , Evaluación de Programas y Proyectos de Salud , Centros de Atención Secundaria , Sudáfrica
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