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1.
Ann Oncol ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39288844

RESUMEN

BACKGROUND: The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and healthcare efficiencies. PATIENTS AND METHODS: CheckMate 67T (NCT04810078) was a phase 3, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20,000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). Primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis (time-averaged serum concentration over the first 28 days [Cavgd28], and minimum steady-state serum concentration [Cminss]; noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios [GMR] ≥0.8). Objective response rate (ORR) was a key secondary endpoint powered for noninferiority (noninferiority threshold: lower boundary of 95% CI of relative risk of ORR [subcutaneous versus intravenous nivolumab] ≥0.60). RESULTS: Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of Cavgd28 and Cminss was 2.098 (90% CI, 2.001-2.200) and 1.774 (90% CI, 1.633-1.927), respectively. After 8 months minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI, 19.0-30.0) versus 18.2% with intravenous nivolumab (95% CI, 13.6-23.6; relative risk: 1.33 [95% CI, 0.94-1.87]). Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar. CONCLUSION: Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39214912

RESUMEN

OBJECTIVE: To analyze the prevalence of hypomineralized second primary molar (HSPM) and its association with socioeconomic characteristics and dental caries in a Brazilian population of preschoolers. MATERIAL AND METHODS: 603 preschoolers, enrolled in public preschools in Itajaí (state of Santa Catarina, Brazil), took part in the study. To assess the participants' socio-economic characteristics, an original questionnaire was formulated and sent to the children's parents. The clinical evaluation was carried out by a calibrated examiner using the deft/DMFT index for dental caries and Ghanim et al. (Ghanim et al., Eur Arch Paediatr Dent, 2015) criteria for HSPM. The data were analyzed through Poisson regression, using STATA statistical software, and the association analyses were presented by prevalence ratios (PR). RESULTS: The prevalence of at least one HSPM-affected second molar was 24.5%. The prevalence of HSPM was associated to the city's geographical regions of the Educational hubs (p < 0.001). A significant association was found between dental caries and HSPM (p = 0.003; PR: 1.31; 95% CI 1.09-1.56). Children with HSPM were 31% more likely to experience dental caries than children without HSPM. Geographical regions of educational hubs were also significantly associated with HSPM (p < 0.001). None of the socioeconomic characteristics was associated with HSPM (p > 0.05). CONCLUSION: HSPM is a common developmental defect of enamel in children in our study. The HSPM distribution was associated with the city's geographic regions. Children with HSPM are more likely to experience dental caries. Socioeconomic characteristics were not associated with HSPM.

3.
Biosystems ; 240: 105229, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38740124

RESUMEN

We study a five-species cyclic system wherein individuals of one species strategically adapt their movements to enhance their performance in the spatial rock-paper-scissors game. Environmental cues enable the awareness of the presence of organisms targeted for elimination in the cyclic game. If the local density of target organisms is sufficiently high, individuals move towards concentrated areas for direct attack; otherwise, they employ an ambush tactic, maximising the chances of success by targeting regions likely to be dominated by opponents. Running stochastic simulations, we discover that the ambush strategy enhances the likelihood of individual success compared to direct attacks alone, leading to uneven spatial patterns characterised by spiral waves. We compute the autocorrelation function and measure how the ambush tactic unbalances the organisms' spatial organisation by calculating the characteristic length scale of typical spatial domains of each species. We demonstrate that the threshold for local species density influences the ambush strategy's effectiveness, while the neighbourhood perception range significantly impacts decision-making accuracy. The outcomes show that long-range perception improves performance by over 60%, although there is potential interference in decision-making under high attack triggers. Understanding how organisms' adaptation their environment enhances their performance may be helpful not only for ecologists, but also for data scientists, aiming to improve artificial intelligence systems.


Asunto(s)
Teoría del Juego , Animales , Simulación por Computador , Toma de Decisiones/fisiología , Humanos , Inteligencia Artificial , Modelos Biológicos
4.
Rev. esp. anestesiol. reanim ; 71(4): 274-281, abril 2024. ilus, tab
Artículo en Español | IBECS | ID: ibc-232122

RESUMEN

Introducción y objetivos: El cáncer de mama es la neoplasia más frecuentemente diagnosticada y el dolor crónico postoperatorio (DCPO) es un problema relacionado con la terapia crecientemente reconocido. Evaluamos la incidencia del DCPO, sus características, factores asociados e impacto en la calidad de vida (CdV) del paciente.Materiales y métodosSe realizó un estudio prospectivo observacional de 6meses en pacientes tratados mediante cirugía de mama en un hospital universitario terciario. Los datos se recopilaron utilizando diversos cuestionarios: Pain Catastrophizing Scale, Brief Pain Inventory-Short Form, Douleur Neuropathique 4, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire y Breast Cancer Module.ResultadosUn total de 112 pacientes completaron el estudio, de los cuales aproximadamente un tercio (34,8%) desarrollaron DCPO y casi todos ellos dolor neuropático potencial. El DCPO interfirió con la vida diaria de los pacientes y redujo su CdV. La diabetes (p=0,028), la catastrofización (p=0,042) y la gravedad del dolor posoperatorio agudo (p<0,001) se asociaron a DCPO.ConclusionesEste estudio amplía nuestra comprensión sobre el DCPO y muestra el impacto de este síndrome. Los profesionales sanitarios deben ser conscientes del DCPO, y tomar medidas para prevenirlo y tratarlo, proporcionando a los pacientes la información suficiente. (AU)


Introduction and objectives: Breast cancer is the most frequently diagnosed malignancy, and chronic pain after breast surgery (CPBS) is an increasingly recognized therapy-related problem. We evaluated CPBS incidence, characteristics, associated factors, and impact on patient quality of life (QoL).Materials and methodsSix-month observational prospective study in patients undergoing breast surgery in a tertiary university hospital. Data were collected using several questionnaires: Pain Catastrophizing Scale, Brief Pain Inventory-Short Form, Douleur Neuropathique 4 Questionnaire, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and its Breast Cancer Module.ResultsA total of 112 patients completed the study. Approximately, one third (34.8%) developed CPBS, almost all with potentially neuropathic pain. CPBS interfered with patients’ daily life and reduced their QoL. Diabetes (p=.028), catastrophizing (p=.042), and acute postoperative pain severity (p<.001) were associated with CPBS.ConclusionsThis study broadens our understanding of CPBS and shows the impact of this syndrome. Healthcare workers need to be aware of CPBS and take steps to prevent and treat it, and provide patients with adequate information. (AU)


Asunto(s)
Humanos , Neoplasias de la Mama , Cirugía General , Dolor Postoperatorio , Calidad de Vida
5.
J Hosp Infect ; 146: 116-124, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38365067

RESUMEN

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii is a common pathogen associated with healthcare-acquired infections, and robust infection prevention and control protocols exist in human healthcare settings. In contrast, infection prevention and control (IPC) standards are limited in veterinary medicine, necessitating further investigation. AIM: Examine the possible transmission of carbapenem-resistant Acinetobacter spp. in a veterinary practice where a cat was diagnosed with an OXA-23-producing A. baumannii ST2 strain. METHODS: Environmental samples together with nasal and hand swabs from the veterinary personnel were collected. All swabs were screened for the presence of extended-spectrum-ß-lactamase- and carbapenemase-producing Enterobacterales, meticillin-resistant staphylococcus and multi-drug-resistant Acinetobacter spp. Whole-genome sequencing was performed for carbapenemase-producing strains. RESULTS: Of the veterinary staff, 60% carried meticillin-resistant Staphylococcus epidermidis. Environmental evaluation showed that 40% (N=6/15) of the surfaces analysed by contact plates and 40% (N=8/20) by swabs failed the hygiene criteria. Assessment of the surfaces revealed contamination with five OXA-23-producing Acinetobacter spp. strains: an OXA-23-producing Acinetobacter schindleri on the weight scale in the waiting room; and four OXA-23-producing Acinetobacter lwoffii strains, on different surfaces of the treatment room. The blaOXA-23 gene was located on the same plasmid-carrying Tn2008 across the different Acinetobacter spp. strains. These plasmids closely resemble a previously described OXA-23-encoding plasmid from a human Portuguese nosocomial Acinetobacter pittii isolate. Distinctly, the OXA-23-producing A. baumannii ST2 clinical strain had the resistant gene located on Tn2006, possibly inserted on the chromosome. CONCLUSION: The detection of an OXA-23-producing A. baumannii ST2 veterinary clinical strain is of concern for companion animal health and infection, prevention and control. This study established the dynamic of transmission of the plasmid-mediated blaOXA-23 gene on critical surfaces of a small animal veterinary practice. The genetic resemblance to a plasmid found in human nosocomial settings suggests a potential One Health link.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Infección Hospitalaria , Staphylococcus aureus Resistente a Meticilina , Salud Única , Animales , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Meticilina , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/prevención & control , Infecciones por Acinetobacter/veterinaria , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , beta-Lactamasas/genética , beta-Lactamasas/análisis , Acinetobacter baumannii/genética , Carbapenémicos , Infección Hospitalaria/prevención & control , Infección Hospitalaria/veterinaria , Antibacterianos
6.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(4): 274-281, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38242359

RESUMEN

INTRODUCTION AND OBJECTIVES: Breast cancer is the most frequently diagnosed malignancy, and chronic pain after breast surgery (CPBS) is an increasingly recognized therapy-related problem. We evaluated CPBS incidence, characteristics, associated factors, and impact on patient quality of life (QoL). MATERIALS AND METHODS: Six-month observational prospective study conducted in patients undergoing breast surgery in a tertiary university hospital. Data were collected using several questionnaires: Pain Catastrophizing Scale, Brief Pain Inventory-Short Form, Douleur Neuropathique 4 Questionnaire, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and its Breast Cancer Module. RESULTS: A total of 112 patients completed the study. Approximately, one third (34.8%) developed CPBS, and almost all with potentially neuropathic pain. CPBS interfered with patients' daily life and reduced their QoL. Diabetes (p = 0.028), catastrophizing (p = 0.042), and acute postoperative pain severity (p < 0.001) were associated with CPBS. CONCLUSIONS: This study broadens our understanding of CPBS and shows the impact of this syndrome. Healthcare workers need to be aware of CPBS and take steps to prevent and treat it, and provide patients with adequate information.


Asunto(s)
Neoplasias de la Mama , Dolor Crónico , Mastectomía , Dolor Postoperatorio , Calidad de Vida , Humanos , Femenino , Dolor Crónico/etiología , Dolor Crónico/epidemiología , Dolor Crónico/psicología , Estudios Prospectivos , Persona de Mediana Edad , Dolor Postoperatorio/psicología , Dolor Postoperatorio/etiología , Dolor Postoperatorio/epidemiología , Incidencia , Factores de Riesgo , Neoplasias de la Mama/cirugía , Mastectomía/efectos adversos , Anciano , Adulto , Dimensión del Dolor
7.
Chaos ; 33(9)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37699118

RESUMEN

We investigate the spatial dynamics of two-disease epidemics reaching a three-species cyclic model. Regardless of their species, all individuals are susceptible to being infected with two different pathogens, which spread through person-to-person contact. We consider that the simultaneous presence of multiple infections leads to a synergistic amplification in the probability of host mortality due to complications arising from any of the co-occurring diseases. Employing stochastic simulations, we explore the ramifications of this synergistic coinfection on spatial configurations that emerge from stochastic initial conditions. Under conditions of pronounced synergistic coinfection, we identify the emergence of zones inhabited solely by hosts affected by a singular pathogen. At the boundaries of spatial domains dominated by a single disease, interfaces of coinfected hosts appear. The dynamics of these interfaces are shaped by curvature-driven processes and display a scaling behavior reflective of the topological attributes of the underlying two-dimensional space. As the lethality linked to coinfection diminishes, the evolution of the interface network's spatial dynamics is influenced by fluctuations stemming from waves of coinfection that infiltrate territories predominantly occupied by a single disease. Our analysis extends to quantifying the implications of synergistic coinfection at both the individual and population levels Our outcomes show that organisms' infection risk is maximized if the coinfection increases the death due to disease by 30% and minimized as the network dynamics reach the scaling regime, with species populations being maximum. Our conclusions may help ecologists understand the dynamics of epidemics and their impact on the stability of ecosystems.


Asunto(s)
Coinfección , Epidemias , Humanos , Coinfección/epidemiología , Ecosistema , Probabilidad
8.
Braz J Biol ; 83: e268540, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37132740

RESUMEN

Detrusor hypocontractility (DH) is a disease without a gold standard treatment in traditional medicine. Therefore, there is a need to develop innovative therapies. The present report presents the case of a patient with DH who was transplanted with 2 x 106 adipose tissue-derived mesenchymal stem cells twice and achieved significant improvements in their quality of life. The results showed that cell therapy reduced the voiding residue from 1,800 mL to 800 mL, the maximum cystometric capacity from 800 to 550 mL, and bladder compliance from 77 to 36.6 mL/cmH2O. Cell therapy also increased the maximum flow from 3 to 11 mL/s, the detrusor pressure from 08 to 35 cmH2O, the urine volume from 267 to 524 mL and the bladder contractility index (BCI) value from 23 to 90. The International Continence on Incontinence Questionnaire - Short Form score decreased from 17 to 8. Given the above, it is inferred that the transplantation of adipose tissue-derived mesenchymal stem cells is an innovative and efficient therapeutic strategy for DH treatment and improves the quality of life of patients affected by this disease.


Asunto(s)
Calidad de Vida , Vejiga Urinaria , Humanos , Células Madre , Tratamiento Basado en Trasplante de Células y Tejidos
9.
Biosystems ; 227-228: 104901, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37121500

RESUMEN

We run stochastic simulations of the spatial version of the rock-paper-scissors game, considering that individuals use sensory abilities to scan the environment to detect the presence of enemies. If the local dangerousness level is above a tolerable threshold, individuals aggregate instead of moving randomly on the lattice. We study the impact of the locally adaptive aggregation on the organisms' spatial organisation by measuring the characteristic length scale of the spatial domains occupied by organisms of a single species. Our results reveal that aggregation is beneficial if triggered when the local density of opponents does not exceed 30%; otherwise, the behavioural strategy may harm individuals by increasing the average death risk. We show that if organisms can perceive further distances, they can accurately scan and interpret the signals from the neighbourhood, maximising the effects of the locally adaptive aggregation on the death risk. Finally, we show that the locally adaptive aggregation behaviour promotes biodiversity independently of the organism's mobility. The coexistence probability rises if organisms join conspecifics, even in the presence of a small number of enemies. We verify that our conclusions hold for more complex systems by simulating the generalised rock-paper-scissors models with five and seven species. Our discoveries may be helpful to ecologists in understanding systems where organisms' self-defence behaviour adapts to local environmental cues.


Asunto(s)
Biodiversidad , Modelos Biológicos , Humanos , Probabilidad
10.
J Biomol Struct Dyn ; 41(24): 14871-14886, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36927332

RESUMEN

The present study focused on investigating the antioxidant, antiglycation activity, digestive enzymes inhibition, bioaccessibility and hypoglycemic effect of C. arabica leaves extracts. The extracts deactivated the O2•-, ROO•, H2O2, HOCl reactive oxygen species. Coffee leaves showed strong inhibition of α-glucosidase (IC50 = 40.30 µg mL-1) greater than the isolated metabolites and acarbose. There was also inhibition of pancreatic lipase (IC50 = 56.43 µg mL-1) in addition to a hypoglycemic effect in zebrafish similar to acarbose and metformin. With the exception of rutin, all biocompounds were detected at all stages of in vitro digestion. Finally, these results suggest that C. arabica leaf extracts possess antidiabetic and anti-obesity properties that can be attributed to the main metabolites and the synergistic action between them.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Antioxidantes , Coffea , Animales , Antioxidantes/farmacología , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Acarbosa , Peróxido de Hidrógeno , Pez Cebra
11.
Eur Arch Paediatr Dent ; 24(1): 43-53, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36125631

RESUMEN

PURPOSE: To evaluate the prevalence of sleep disorders in Brazilian preschool children and its associations with parental report of dental pain and discomfort. METHODS: This cross-sectional study involved 604 Brazilian preschoolers (4-5 years old). Sleep disorders (SD) and the parental report of dental pain and discomfort (DPD) were evaluated using the Brazilian versions of the Sleep Disturbance Scale for Children (SDSC) and the Dental Discomfort Questionnaire (DDQ-B), respectively. Bivariate and multivariate Poisson regression analyses with robust variance were performed to analyze the association between SDSC and DP. RESULTS: Prevalence of SD ranged from 7 to 21%. 7.9% of the children had DPD indicating the need for more invasive dental procedures (DDQ-B ≥ 5). Significant associations were found between DPD and the following SDSC domains: sleep hyperhidrosis (p = 0.024; PRa = 1.38; 95% CI: 1.04-1.83), disorders of initiating and maintaining sleep (p < 0.001; PRa = 1.41; 95% CI: 1.15-1.73), parasomnias (p < 0.001; PRa = 1.82; 95% CI: 1.39-2.37), and sleep-wake transition disorders (p = 0.018; PRa = 1.28; 95% CI: 1.04-1.58). Children with higher prevalence of DPD presented 20% higher prevalence of SD than children lower prevalence of DPD (p = 0.039; PRa = 1.20; 95% CI: 1.01-1.44). CONCLUSION: Preschool children with higher prevalence of DPD are more likely to have SD, such as hyperhidrosis, disorders of initiating and maintaining sleep, parasomnias, and sleep-wake transition.


Asunto(s)
Hiperhidrosis , Parasomnias , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Preescolar , Humanos , Brasil/epidemiología , Estudios Transversales , Hiperhidrosis/complicaciones , Dolor/complicaciones , Parasomnias/complicaciones , Padres , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/complicaciones , Encuestas y Cuestionarios , Odontología Pediátrica
12.
Biosystems ; 221: 104777, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36070849

RESUMEN

We study a three-species cyclic game system where organisms face a contagious disease whose virulence may change by a pathogen mutation. As a responsive defence strategy, organisms' mobility is restricted to reduce disease dissemination in the system. The impact of the collective self-preservation strategy on the disease infection risk is investigated by performing stochastic simulations of the spatial version of the rock-paper-scissors game. Our outcomes show that the mobility control strategy induces plasticity in the spatial patterns with groups of organisms of the same species inhabiting spatial domains whose characteristic length scales depend on the level of dispersal restrictions. The spatial organisation plasticity allows the ecosystems to adapt to minimise the individuals' disease contamination risk if an eventual pathogen alters the disease virulence. We discover that if a pathogen mutation makes the disease more transmissible or less lethal, the organisms benefit more if the mobility is not strongly restricted, thus forming large spatial domains. Conversely, the benefits of protecting against a pathogen causing a less contagious or deadlier disease are maximised if the average size of groups of individuals of the same species is significantly limited, reducing the dimensions of groups of organisms significantly. Our findings may help biologists understand the effects of dispersal control as a conservation strategy in ecosystems affected by epidemic outbreaks.


Asunto(s)
Ecosistema , Modelos Biológicos , Humanos
13.
Biosystems ; 217: 104689, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35500816

RESUMEN

Disease outbreaks affect many ecosystems threatening species that also fight against other natural enemies. We investigate a cyclic game system with 5 species, whose organisms outcompete according to the rules of a generalised spatial rock-paper-scissors game, during an epidemic. We study the effects of behavioural movement strategies that allow individuals of one out of the species to move towards areas with a low density of disease vectors and a high concentration of enemies of their enemies. We perform a series of stochastic simulations to discover the impact of self-preservation strategies in pattern formation, calculating the species' spatial autocorrelation functions. Considering organisms with different physical and cognitive abilities, we compute the benefits of each movement tactic to reduce selection and infection risks. Our findings show that the maximum profit in terms of territorial dominance in the cyclic game is achieved if both survival movement strategies are combined, with individuals prioritising social distancing. In the case of an epidemic causing symptomatic illness, the drop in infection risk when organisms identify and avoid disease vectors does not render a rise in the species population because many refuges are disregarded, limiting the benefits of safeguarding against natural enemies. Our results may be helpful to the understanding of the behavioural strategies in ecosystems where organisms adapt to face living conditions changes.


Asunto(s)
Epidemias , Teoría del Juego , Ecosistema , Epidemias/prevención & control , Humanos , Movimiento
14.
Chaos ; 32(12): 123142, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36587336

RESUMEN

Antipredator behavior is a self-preservation strategy present in many biological systems, where individuals join the effort in a collective reaction to avoid being caught by an approaching predator. We study a nonhierarchical tritrophic system, whose predator-prey interactions are described by the rock-paper-scissors game rules. We perform a set of spatial stochastic simulations where organisms of one out of the species can resist predation in a collective strategy. The drop in predation capacity is local, which means that each predator faces a particular opposition depending on the prey group size surrounding it. Considering that the interference in a predator action depends on the prey's physical and cognitive ability, we explore the role of a conditioning factor that indicates the fraction of the species apt to perform the antipredator strategy. Because of the local unbalancing of the cyclic predator-prey interactions, departed spatial domains mainly occupied by a single species emerge. Unlike the rock-paper-scissors model with a weak species because of a nonlocal reason, our findings show that if the predation probability of one species is reduced because individuals face local antipredator response, the species does not predominate. Instead, the local unbalancing of the rock-paper-scissors model results in the prevalence of the weak species' prey. Finally, the outcomes show that local unevenness may jeopardize biodiversity, with the coexistence being more threatened for high mobility.


Asunto(s)
Biodiversidad , Modelos Biológicos , Humanos , Animales , Conducta Predatoria/fisiología
16.
Phys Rev E ; 104(5-1): 054201, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34942823

RESUMEN

Antipredator behavior is present in many biological systems where individuals collectively react to an imminent attack. The antipredator response may influence spatial pattern formation and ecosystem stability but requires an organism's cost to contribute to the collective effort. We investigate a nonhierarchical tritrophic system, whose predator-prey interactions are described by the rock-paper-scissors game rules. In our spatial stochastic simulations, the radius of antipredator response defines the maximum prey group size that disturbs the predator's action, determining the individual cost to participate in antipredator strategies. We consider that each organism contributes equally to the collective effort, having its mobility limited by the proportion of energy devoted to the antipredator reaction. Our outcomes show that the antipredator response leads to spiral patterns, with the segregation of organisms of the same species occupying departed spatial domains. We found that a less localized antipredator response increases the average size of the single-species patches, improving the protection of individuals against predation. Finally, our findings show that although the increase of the predation risk for a more localized antipredator response, the high mobility constraining benefits species coexistence. Our results may help ecologists understand the mechanisms leading to the stability of biological systems where locality is crucial to behavioral interactions among species.

17.
ESMO Open ; 6(5): 100273, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34607285

RESUMEN

BACKGROUND: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. PATIENTS AND METHODS: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. RESULTS: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. CONCLUSIONS: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Ipilimumab/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia , Nivolumab/efectos adversos
18.
Sci Rep ; 11(1): 14029, 2021 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-34234237

RESUMEN

Toxoplasma gondii is an opportunistic protozoan pathogen with a wide geographic distribution. The chronic phase of toxoplasmosis is often asymptomatic in humans and is characterized by tissue cysts throughout the central nervous system and muscle cells. T. gondii and other pathogens with tropism for the central nervous system are considered risk factors in the etiology of several neuropsychiatric disorders, such as schizophrenia and bipolar disorder, besides neurological diseases. Currently, it is known that cerebral toxoplasmosis increases dopamine levels in the brain and it is related to behavioral changes in animals and humans. Here we evaluate whether chronic T. gondii infection, using the cystogenic ME-49 strain, could induce behavioral alterations associated with neuropsychiatric disorders and glutamatergic neurotransmission dysfunction. We observed that the startle amplitude is reduced in the infected animals as well as glutamate and D-serine levels in prefrontal cortical and hippocampal tissue homogenates. Moreover, we did not detect alterations in social preference and spontaneous alternation despite severe motor impairment. Thus, we conclude that behavioral and cognitive aspects are maintained even though severe neural damage is observed by chronic infection of C57Bl/6 mice with the ME-49 strain.


Asunto(s)
Ácido Glutámico/metabolismo , Trastornos Mentales/etiología , Trastornos Mentales/metabolismo , Reflejo de Sobresalto , Serina/metabolismo , Toxoplasmosis Cerebral/complicaciones , Toxoplasmosis Cerebral/parasitología , Animales , Conducta Animal , Peso Corporal , Encéfalo/metabolismo , Encéfalo/parasitología , Encéfalo/patología , Hipocampo/metabolismo , Trastornos Mentales/diagnóstico , Trastornos Mentales/psicología , Ratones , Neurotransmisores/metabolismo , Corteza Prefrontal/metabolismo , Conducta Social , Toxoplasma
19.
Phys Rev E ; 103(5-1): 052216, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34134300

RESUMEN

When faced with an imminent risk of predation, many animals react to escape consumption. Antipredator strategies are performed by individuals acting as a group to intimidate predators and minimize the damage when attacked. We study the antipredator prey response in spatial tritrophic systems with cyclic species dominance using the rock-paper-scissors game. The impact of the antipredator behavior is local, with the predation probability reducing exponentially with the number of prey in the predator's neighborhood. In contrast to the standard Lotka-Volterra implementation of the rock-paper-scissors model, where no spiral waves appear, our outcomes show that the antipredator behavior leads to spiral patterns from random initial conditions. The results show that the predation risk decreases exponentially with the level of antipredator strength. Finally, we investigate the coexistence probability and verify that antipredator behavior may jeopardize biodiversity for high mobility. Our findings may help biologists to understand ecosystems formed by species whose individuals behave strategically to resist predation.

20.
Sci Rep ; 11(1): 6413, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33742025

RESUMEN

The spatial segregation of species is fundamental to ecosystem formation and stability. Behavioural strategies may determine where species are located and how their interactions change the local environment arrangement. In response to stimuli in the environment, individuals may move in a specific direction instead of walking randomly. This behaviour can be innate or learned from experience, and allow the individuals to conquer or the maintain territory, foraging or taking refuge. We study a generalisation of the spatial rock-paper-scissors model where individuals of one out of the species may perform directional movement tactics. Running a series of stochastic simulations, we investigate the effects of the behavioural tactics on the spatial pattern formation and the maintenance of the species diversity. We also explore a more realistic scenario, where not all individuals are conditioned to perform the behavioural strategy or have different levels of neighbourhood perception. Our outcomes show that self-preservation behaviour is more profitable in terms of territorial dominance, with the best result being achieved when all individuals are conditioned and have a long-range vicinity perception. On the other hand, invading is more advantageous if part of individuals is conditioned and if they have short-range neighbourhood perception. Finally, our findings reveal that the self-defence strategy is the least jeopardising to biodiversity which can help biologists to understand population dynamics in a setting where individuals may move strategically.

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