RESUMEN
BACKGROUND: Delays in clinical trial enrollment and difficulties enrolling representative samples continue to vex sponsors, sites, and patient populations. Here we investigated use of an artificial intelligence-powered technology, Mendel.ai, as a means of overcoming bottlenecks and potential biases associated with standard patient prescreening processes in an oncology setting. METHODS: Mendel.ai was applied retroactively to 2 completed oncology studies (1 breast, 1 lung), and 1 study that failed to enroll (lung), at the Comprehensive Blood and Cancer Center, allowing direct comparison between results achieved using standard prescreening practices and results achieved with Mendel.ai. Outcome variables included the number of patients identified as potentially eligible and the elapsed time between eligibility and identification. RESULTS: For each trial that enrolled, use of Mendel.ai resulted in a 24% to 50% increase over standard practices in the number of patients correctly identified as potentially eligible. No patients correctly identified by standard practices were missed by Mendel.ai. For the nonenrolling trial, both approaches failed to identify suitable patients. An average of 19 days for breast and 263 days for lung cancer patients elapsed between actual patient eligibility (based on clinical chart information) and identification when the standard prescreening practice was used. In contrast, ascertainment of potential eligibility using Mendel.ai took minutes. CONCLUSIONS: This study suggests that augmentation of human resources with artificial intelligence could yield sizable improvements over standard practices in several aspects of the patient prescreening process, as well as in approaches to feasibility, site selection, and trial selection.
Asunto(s)
Inteligencia Artificial , Ensayos Clínicos como Asunto , Neoplasias , Selección de Paciente , Humanos , Neoplasias/tratamiento farmacológico , TiempoRESUMEN
Se desarrolló el modelo matemático correspondiente al Coeficiente de Operación (COP) del ciclo de Carnot para una bomba de calor endorreversible, aplicando el criterio de mínima generación de entropía. Este ciclo tiene como características principales ser internamente reversible y externamente irreversible. Las irreversibilidades externas están asociadas a los procesos de transferencia de calor debido a la diferencia de temperaturas entre la fuente térmica y el fluido de trabajo a baja temperatura, y a la diferencia de temperaturas entre el fluido de trabajo y el sumidero térmico a alta temperatura. También son causantes de las irreversibilidades externas los tiempos finitos de duración de los procesos de transferencia de calor y las conductancias térmicas finitas de los equipos de transferencia de calor (evaporador y condensador). Estas causas de irreversibilidades aparecen en el modelo matemático desarrollado y por esto se propone como nuevo modelo de comparación para las bombas de calor, en lugar del modelo clásico de Coeficiente de Operación de Carnot de bomba de calor reversible. Este nuevo modelo marca límites de operación más cercanos a las bombas de calor reales. El modelo obtenido viene a ser una contribución al desarrollo de la termodinámica endorreversible y se puede considerar una generalización, porque cuando se aplican las condiciones de reversibilidades internas y externas, se llega al mismo resultado que el clásico de Carnot.
Asunto(s)
Bombas , IngenieríaRESUMEN
The antinociceptive effect of purine nucleotides administered systematically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10, of 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that antinociceptive effect of adenine nucleotides is mediated by adenosine.
Asunto(s)
Nociceptores/efectos de los fármacos , Nucleótidos de Purina/farmacología , Analgésicos/farmacología , Animales , Cafeína/farmacología , Masculino , Ratones , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Quinidina/farmacología , Receptores Purinérgicos P1/efectos de los fármacos , Receptores Purinérgicos P2/efectos de los fármacos , Colorantes de Rosanilina/farmacología , Suramina/farmacología , Teofilina/farmacologíaRESUMEN
The antinociceptive effect of purine nucleotides administered systemically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10 or 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that the antinociceptive effect of adenine nucleotides is mediated by adenosine.
Asunto(s)
Ratones , Animales , Masculino , Analgésicos/farmacología , Cafeína/farmacología , Inflamación/tratamiento farmacológico , Naloxona/farmacología , Quinidina/farmacología , Colorantes de Rosanilina/farmacología , Suramina/farmacología , Teofilina/farmacología , Receptores Purinérgicos P1/efectos de los fármacos , Receptores Purinérgicos P2/efectos de los fármacosRESUMEN
Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Ácido Glutámico/farmacología , Guanosina Monofosfato/farmacología , Hipocampo/fisiología , Neuronas/fisiología , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Ratas , Ratas Wistar , Membranas Sinápticas/efectos de los fármacos , Membranas Sinápticas/metabolismoRESUMEN
The effect of intrastriatal administration of methylmalonic acid (MMA), a metabolite that accumulates in methylmalonic aciduria, on behavior of adult male Wistar rats was investigated. After cannula placing, rats received unilateral intrastriatal injections of MMA (buffered to pH 7.4 with NaOH) or NaCl. MMA induced rotational behavior toward the contralateral side of injection and clonic convulsions in a dose-dependent manner. Rotational behavior and convulsions were prevented by intrastriatal preadministration of MK-801 and attenuated by preadministration of succinate. This study provides evidence for a participation of NMDA receptors in the MMA-induced behavioral alterations, where succinate dehydrogenase inhibition seems to have a pivotal role.