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OBJECTIVE: In Ethiopia, information about health system responsiveness (HSR) in conflict-affected areas is limited. No previous local study was conducted on the assessment of HSR at the community level. Hence, the study assessed HSR for intrapartum care in conflict-affected areas in Amhara region, Ethiopia. DESIGN: Community-based cross-sectional study design. SETTING: Wadila, Gayint and Meket districts, Amhara region, Ethiopia. PARTICIPANTS: The participants were 419 mothers who gave birth in conflict-affected areas within the last 6 months. The study included all mothers who gave birth at health facilities but excluded those who delivered at home, critically ill or unable to hear. OUTCOME: HSR was the outcome variable. In this regard, the study assessed how mothers were treated and the situation in which they were cared for in relation to their experience during the conflict. METHODS: We conducted the study in the community, where we analysed eight domains of HSR to identify 30 measurement items related to intrapartum care responsiveness. The domains we looked at were dignity (4), autonomy (4), confidentiality (2), communication (5), prompt attention (5), social support (3), choice (3) and basic amenities (4). We used a multiple linear regression model to analyse the data, and in this model, we used an unstandardized ß coefficient with a 95% CI and a p value of less than 0.05 to determine the factors significantly associated with HSR. RESULTS: The findings of our study revealed that the overall proportion of HSR in intrapartum care was 45.11% (95% CI: 40.38 to 49.92). The performance of responsiveness was the lowest in the autonomy, choice and prompt attention domains at 35.5%, 49.4% and 52.0%, respectively. Mothers living in urban areas (ß=4.28; 95% CI: 2.06 to 6.50), government employees (ß=4.99; 95% CI: 0.51 to 9.48), those mothers stayed at the health facilities before delivery/during conflict (ß=0.22; 95% CI: 0.09 to 0.35), those who were satisfied with the healthcare service (ß=0.69; 95% CI: 0.08 to 1.30) and those who perceived the quality of healthcare favourable (ß=0.96; 95% CI: 0.72 to 1.19) were more likely to rate HSR positively. On the other hand, joint decision-making for health (ß=-2.46; 95% CI: -4.81 to -0.10) and hospital delivery (ß=-3.62; 95% CI: -5.60 to -1.63) were negatively associated with HSR. CONCLUSION: In the Amhara region of Ethiopia, over 50% of mothers living in areas affected by conflict reported that health systems were not responsive with respect to intrapartum care. Therefore, all stakeholders should work together to ensure that intrapartum care is responsive to conflict-affected areas, with a focus on providing women autonomy and choice.
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Apoio Social , Humanos , Etiópia , Estudos Transversais , Feminino , Adulto , Gravidez , Adulto Jovem , Parto Obstétrico , Serviços de Saúde Materna/normas , Conflitos Armados , Adolescente , Confidencialidade , Autonomia Pessoal , Comunicação , Assistência Perinatal/normasRESUMO
We report a functional pipeline for facile conversion of variable Fv domains, typically discovered in antibody discovery programs, into chimeric monoclonal antibodies (mAbs). Often, in initial screenings, a set of candidate mAbs is produced in small volumes and purified from supernatant for testing. Our pipeline also simplifies purification of mAbs by using an extended histidine tag (His-10) fused to the C-terminus of the light chain. Both the length of the His-10 and its location have been shown to affect the efficacy of mAb purification using an inexpensive nickel-based resin at neutral pH. Our antibody cloning and purification pipeline, when followed together with detection and affinity measurements, can be smoothly incorporated into an antibody discovery workflow.
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Eleven patients (5 men, 6 women) with post-operative thoracic duct injuries and high output chylothorax were treated with thoracic duct embolization (TDE). Six patients underwent intraprocedural thoracic duct ligation at the time of original procedure. In all cases, the pleural fluid demonstrated high triglyceride levels (414 mg/dL; interquartile range [IQR], 345 mg/dL). Median daily (IQR) chest tube outputs before and after TDE were 900 mL (1,200 mL) and 325 mL (630 mL), respectively. Coil- or plug-assisted ethylene vinyl alcohol (EVOH) copolymer was used as embolic agent in all patients. Technical and clinical success rates were 100% and 82%, respectively. Nontarget venous embolization of EVOH copolymer was not identified on subsequent imaging.
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Quilotórax , Embolização Terapêutica , Traumatismos Torácicos , Masculino , Humanos , Feminino , Quilotórax/diagnóstico por imagem , Quilotórax/etiologia , Quilotórax/terapia , Embolização Terapêutica/métodos , Ducto Torácico/diagnóstico por imagem , Estudos Retrospectivos , Traumatismos Torácicos/terapia , Resultado do TratamentoRESUMO
Background: Everolimus is an inhibitor of mammalian target of rapamycin complex 1. As mutations in TSC1 and TSC2, which cause partial-onset seizures associated with TSC, were found in focal cortical dysplasia type â ¡ (FCD â ¡) patients, a clinical trial has been performed to explore the efficacy and safety of everolimus in FCD patients. However, no dosage regimen was determined to treat FCD II. To recommend an optimal dose regimen for FCD patients, a population pharmacokinetic model of everolimus in FCD patients was developed. Methods: The data of everolimus were collected from September 2017 to May 2020 in a tertiary-level hospital in Korea. The model was developed using NONMEM® software version 7.4.1 (Icon Development Solutions, Ellicott City, MD, United States). Results: The population pharmacokinetics of everolimus was described as the one-compartment model with first-order absorption, with the effect of BSA on clearance. The final model was built as follows: TVCL = 12.5 + 9.71 × (BSA/1.5), TVV = 293, and TVKA = 0.585. As a result of simulation, a dose higher than 7 mg/m2 is needed in patients with BSA 0.5 m2, and a dose higher than 6 mg/m2 is needed in patients with BSA 0.7 m2. A dose of 4.5 mg/m2 is enough in the population with BSA higher than 1.5 m2 to meet the target trough range of 5-15 ng/mL. Conclusion: Based on the developed pharmacokinetics model, the optimal dose of everolimus in practice was recommended by considering the available strengths of Afinitor disperz®, 2 mg, 3 mg, and 5 mg.
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OBJECTIVE: Human epidermal growth factor receptor 2 (HER2) is an important biomarker for targeted gastric cancer (GC) immunotherapy. However, heterogeneous HER2 overexpression in GC, loss of HER2 expression during therapy, and inability to non-invasively identify HER2 overexpressing tumors impede effective targeting therapies. Improved HER2-specific functional imaging can address these challenges. Trastuzumab is a HER2-directed mAb to treat HER2 overexpressing cancers. The 64 Cu-DOTA-trastuzumab radiotracer is used to detect HER2+ metastatic breast cancer. We aimed to develop 64 Cu-DOTA-trastuzumab PET-CT to detect and characterize tumor uptake in HER2+ or - GC patients. METHODS: We conducted a single-arm phase II pilot study exploring the feasibility of 64 Cu-DOTA-trastuzumab for PET imaging of HER2 overexpressing GC compared to HER2 non-expressing tumors. Eight patients with biopsy-confirmed gastric adenocarcinoma were included. Immunohistochemistry was used to evaluate primary tumor biopsies for HER2 overexpression. Patients were injected with 45â mg of cold trastuzumab followed by 5â mg of 64 Cu-DOTA-trastuzumab. PET-CT scans were performed 24-48â h post radiotracer injection and compared to standard staging CT scans. RESULTS: We observed limited toxicity following 64 Cu-DOTA-trastuzumab injections. While there was uptake of the radiotracer in portions of HER2+ lesions, there was no statistically significant distinction between tumor and background by standardized uptake value analysis. CONCLUSION: Despite the potential of 64 Cu-DOTA-trastuzumab PET imaging of HER2+ metastatic breast cancer, a 5â mg dose of this radiotracer injected 24-48â h before imaging was insufficient to identify HER2+ GC. These results inform future GC imaging studies to optimize biomarker-targeted therapies based on dosage and timing for more clinically relevant imaging.
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Neoplasias da Mama , Neoplasias Gástricas , Humanos , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Projetos Piloto , Neoplasias Gástricas/diagnóstico por imagem , Trastuzumab , Receptor ErbB-2/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Mama/patologiaRESUMO
BACKGROUND: Nanoliposomal irinotecan (nal-IRI) is a promising novel hyperthermic intraperitoneal chemotherapy (HIPEC) agent given its enhanced efficacy against gastrointestinal tumors, safety profile, thermo-synergy, and heat stability. This report describes the first in-human phase 1 clinical trial of nal-IRI during cytoreductive surgery (CRS) and HIPEC. METHODS: Patients with peritoneal surface disease (PSD) from appendiceal and colorectal neoplasms were enrolled in a 3 + 3 dose-escalation trial using nal-IRI (70-280 mg/m2) during HIPEC for 30 min at 41 ± 1 °C. The primary outcome was safety. The secondary outcomes were pharmacokinetics (PK) and disease-free survival. Adverse events (AEs) categorized as grade 2 or higher were recorded. The serious AEs (SAEs) were mortality, grade ≥ 3 AEs, and dose-limiting toxicity (DLT). Irinotecan and active metabolite SN38 were measured in plasma and peritoneal washings. RESULTS: The study enrolled 18 patients, who received nal-IRI during HIPEC at 70 mg/m2 (n = 3), 140 mg/m2 (n = 6), 210 mg/m2 (n = 3), and 280 mg/m2 (n = 6). No DLT or mortality occurred. The overall morbidity for CRS/HIPEC was 39% (n = 7). Although one patient experienced neutropenia, no AE (n = 131) or SAE (n = 3) was definitively attributable to nal-IRI. At 280 mg/m2, plasma irinotecan and SN38 measurements showed maximum concentrations of 0.4 ± 0.6 µg/mL and 3.0 ± 2.4 ng/mL, a median time to maximum concentration of 24.5 and 26 h, and areas under the curve of 22.6 h*µg/mL and 168 h*ng/mL, respectively. At the 6-month follow-up visit, 83% (n = 15) of the patients remained disease-free. CONCLUSIONS: In this phase 1 HIPEC trial (NCT04088786), nal-IRI was observed to be safe, and PK profiling showed low systemic absorption overall. These data support future studies testing the efficacy of nal-IRI in CRS/HIPEC.
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Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Irinotecano/uso terapêutico , Terapia Combinada , Temperatura Alta , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasias Colorretais/patologia , Hipertermia Induzida/efeitos adversos , Taxa de SobrevidaRESUMO
The study aims to prove that it takes less time to look up relevant clinical history from an electronic medical record (EMR) if the information is already provided in a specific space in the EMR by a fellow radiologist. Patients with complex oncological and surgical histories need frequent imaging, and every time a radiologist may spend a significant amount of time looking up the same clinical information as their peers. In collaboration with ACMIO and Radiant Epic team, a space labeled "Specialty Comments" was added to the SNAPSHOT of patient's chart in EMR. For our research purpose, the specialty comment was labeled as boxed history as a variable for data analysis. If the history was not provided in that particular space, it was labeled as without boxed history. Inclusion criteria included outpatients with complex oncological histories undergoing CT chest, abdomen, and pelvis with IV contrast. The time to look up history (LUT) was documented in minutes and seconds. Two assistant professors from Abdominal Imaging provided LUT. A total of 85 cases were included in the study, 39 with boxed history and 46 without boxed history. Comparing averages of the individual reader means for history, mean LUT differed by 2.03 min (without boxed history) versus 0.57 min (with boxed history), p < 0.0001. The t-test and the nonparametric Wilcoxon tests for a difference in the population means were highly significant (p < 0.0001). A history directed to radiologist's needs resulted in a statistically significant decrease in time spent by interpreting radiologists to look through the electronic medical records for patients with complex oncological histories. Availability of history pertinent to radiology has wide-ranging advantages, including quality reporting, decrease in turnaround time, reduction in interpretation errors, and radiologists' continued learning. The space for documenting clinical history may be reproduced, or some similar area may be developed by optimizing the electronic medical records.
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Registros Eletrônicos de Saúde , Radiologia , Humanos , Radiologistas , Tomografia Computadorizada por Raios X , AbdomeRESUMO
BACKGROUND/AIM: To identify the imaging and clinical features of hepatic neuroendocrine tumors (NETs) associated with peritumoral hyperintensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging. PATIENTS AND METHODS: Fifty-seven patients with hepatic NETs were enrolled. Based on the degree of peritumoral hyperintensity, patients were divided into three groups: group 0 (no peritumoral hyperintensity), group 1 (lower peritumoral hyperintensity), and group 2 (higher peritumoral hyperintensity). The imaging and clinical findings were compared among the three groups. RESULTS: Apparent diffusion coefficient (ADC) values of group 2 were significantly lower than those of group 0 and group 1. Atypical (cholangiocarcinoma-like) enhancement pattern in the arterial phase was significantly more frequently observed in group 2 as compared to that in group 0 and group 1. Group 2 patients showed significantly poorer progression-free survival than group 0 patients. CONCLUSION: Hepatic NETs with greater peritumoral hyperintensity exhibit greater malignant potential.
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Imagem de Difusão por Ressonância Magnética , Neoplasias Hepáticas/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Diagnóstico Diferencial , Feminino , Gadolínio DTPA , Humanos , Aumento da Imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Intervalo Livre de ProgressãoRESUMO
We hypothesized that functional imaging with 64Cu-DOTA-trastuzumab PET/CT would predict the response to the antibody-drug conjugate trastuzumab-emtansine (T-DM1). Methods: Ten women with metastatic human epidermal growth factor receptor 2-positive breast cancer underwent 18F-FDG PET/CT and 64Cu-DOTA-trastuzumab PET/CT on days 1 and 2 before treatment with T-DM1. Results: T-DM1-responsive patients had higher uptake than nonresponsive patients. Day 1 minimum SUVmax (5.6 vs. 2.8, P < 0.02), day 2 minimum SUVmax (8.1 vs. 3.2, P < 0.01), and day 2 average SUVmax (8.5 vs. 5.4, P < 0.05) for 64Cu-DOTA-trastuzumab all favored responding patients. Tumor-level response suggested threshold dependence on SUVmax Patients with a day 2 minimum SUVmax above versus below the threshold had a median time to treatment failure of 28 mo versus 2 mo (P < 0.02). Conclusion: Measurement of trastuzumab uptake in tumors via PET/CT is promising for identifying patients with metastatic breast cancer who will benefit from T-DM1.
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Neoplasias da Mama , Ado-Trastuzumab Emtansina , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Compostos Heterocíclicos com 1 Anel , Humanos , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêuticoRESUMO
PURPOSE: The hand has unique skin characteristics. Intrinsic flap donors are limited due to functional specificity and compactly connected structures. The hypothenar area is a reliable option for the reconstruction of finger defects. We performed anatomic studies elucidating the blood supply of this area and hypothesized that the fourth common palmar digital artery perforator free flap can be used to reconstruct soft tissue defects in fingers with minimal donor site morbidity. METHODS: From November 2017 to February 2020, 30 procedures of fourth common digital artery perforator free flaps were performed to cover digital skin defects. A retrospective chart review was performed, and the cases were analyzed. RESULTS: The mean patient age was 42.4 years (range, 1-75 years; median age, 40 years). Defects were located at the fingertip (n = 12), the dorsum (n = 3), the palmar (n = 9) aspect of the finger, and both the dorsal and palmar aspects of the finger (n = 6). Indications included emergent coverage (n = 13), coverage after necrosis (n = 11), oncological resection (n = 1), and contracture release (n = 5). The defect size ranged from 1.5 × 0.8 cm (1.2 cm2) to 6 × 2.5 cm (15 cm2). The perforator was located approximately 1 cm proximal to the distal palmar crease as it arose from the fourth common digital artery at a right angle. It continued to the ulnar border of the hand through the superficial fascia of the hypothenar muscles before running in a proximoulnar direction toward the dorsum of the hand. The diameter of the perforator was between 0.5 and 0.7 mm. All flaps survived. One case required a split-thickness skin graft for donor site closure, and all others could be closed primarily. CONCLUSIONS: The fourth common digital artery perforator is a versatile flap and can be used for both palmar and dorsal defects, including for the fingertip. The location of the perforator used differs from previous descriptions but is routinely and reliably located. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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Traumatismos dos Dedos , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Humanos , Adulto , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Traumatismos dos Dedos/cirurgia , Estudos Retrospectivos , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Artéria Ulnar/cirurgia , Transplante de Pele/métodos , Resultado do TratamentoRESUMO
The Kuramoto model exhibits different types of synchronization transitions depending on the type of natural frequency distribution. To obtain these results, the Kuramoto self-consistency equation (SCE) approach has been used successfully. However, this approach affords only limited understanding of more detailed properties such as the stability. Here we extend the SCE approach by introducing an effective potential, that is, an integral version of the SCE. We examine the landscape of this effective potential for second-order, first-order, and hybrid synchronization transitions in the thermodynamic limit. In particular, for the hybrid transition, we find that the minimum of effective potential displays a plateau across the region in which the order parameter jumps. This result suggests that the effective potential can be used to determine a type of synchronization transition.
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Phase transitions (PTs) are generally classified into second-order and first-order transitions, each exhibiting different intrinsic properties. For instance, a first-order transition exhibits latent heat and hysteresis when a control parameter is increased and then decreased across a transition point, whereas a second-order transition does not. Recently, hybrid percolation transitions (HPTs) are issued in diverse complex systems, in which the features of first-order and second-order PTs occur at the same transition point. Thus, the question whether hysteresis appears in an HPT arises. Herein, we investigate this fundamental question with a so-called restricted Erdos-Rényi random network model, in which a cluster fragmentation process is additionally proposed. A hysteresis curve of the order parameter was obtained. Depending on when the reverse process is initiated, the shapes of hysteresis curves change, and the critical behavior of the HPT is conserved throughout the forward and reverse processes.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Understanding of a hybrid percolation transitions (HPTs) induced by cluster coalescence, exhibiting a jump in the giant cluster size and a critical behavior of finite clusters, is fundamental and intriguing. Here, we uncover the underlying mechanism using the so-called restricted-random network model, in which clusters are ranked by size and partitioned into small- and large-cluster sets. As clusters are merged and their rankings are updated, they may move back and forth across the set boundary. The intervals of these crossings exhibit a self-organized critical (SOC) behavior with two power-law exponents. During this process, a bump is formed and eliminated in the cluster size distribution, characterizing the criticality of the HPT. This SOC behavior is in contrast to the critical branching process, which governs the avalanche dynamics of the HPT in the pruning process. Finally, we find that a burst of such crossing events occurs and signals the upcoming abrupt transition.
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PURPOSE: Response assessment with computed tomography after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) is challenging because myriad anatomic changes can occur after treatment. Diffusion-weighted magnetic resonance imaging (MRI) may provide additional data to guide therapy response. The primary objective was to evaluate the effect of SBRT on the mean apparent diffusion coefficient (ADC). METHODS AND MATERIALS: This is a prospective clinical study of patients with NSCLC who received SBRT to the primary lung lesion. Patients underwent MRI scans before and at 1 month after completion of SBRT. MRI consisted of T1- and T2-weighted sequences, along with postcontrast, dynamic-contrast, and diffusion-weighted sequences with construction of ADC maps. Two blinded radiologists generated the ADC. SBRT was given over 5 fractions. RESULTS: A total of 13 patients were enrolled. Twelve patients were eligible for analysis. An average increase of 50% and 46% in mean single-plane ADC was observed after treatment by readers 1 and 2, respectively (P < .01, both reviewers). There was good interobserver agreement of single-plane ADC values between the 2 radiologists (Pearson correlation of 0.85 [baseline] and 0.89 [1-month post-SBRT], P < .001 for both). There was also a significant 18% increase in mean volumetric ADC on the 1-month scan (Wilcoxon P = .02). Two patients developed a local failure after SBRT, 1 at 6 months and the other at 34 months. Using a threshold of volumetric ADC increase of greater than 40%, 2 of 2 patients demonstrated local failure compared with 0 of 10 patients below this limit. CONCLUSIONS: A statistically significant increase in ADC was observed 1 month after treatment. An ADC increase of 40% at 1 month was associated with a higher rate of local failure. This pilot study provides impetus for studying ADC as a radiomic biomarker in patients receiving lung SBRT for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia , Variações Dependentes do Observador , Projetos Piloto , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Radiocirurgia , Estatísticas não Paramétricas , Fatores de Tempo , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
BACKGROUND: Pancreatic cancer (PC) hijacks innate cellular processes to promote cancer growth. We hypothesized that PC exploits PD-1/PD-L1 not only to avoid immune responses, but to directly enhance growth. We also hypothesized that immune checkpoint inhibitors (ICIs) have direct cytotoxicity in PC. We sought to elucidate therapeutic targeting of PD-1/PD-L1. METHODS: PD-1 was assessed in PC cells, patient-derived organoids (PDOs), and clinical tissues. Then, PC cells were exposed to PD-L1 to evaluate proliferation. To test PD-1/PD-L1 signaling, cells were exposed to PD-L1 and MAPK was examined. Radio-immunoconjugates with anti-PD-1 drugs were developed to test uptake in patient-derived tumor xenografts (PDTXs). Next, PD-1 function was assessed by xenografting PD-1-knockdown cells. Finally, PC models were exposed to ICIs. RESULTS: PD-1 expression was demonstrated in PCs. PD-L1 exposure increased proliferation and activated MAPK. Imaging PDTXs revealed uptake of radio-immunoconjugates. PD-1 knockdown in vivo revealed 67% smaller volumes than controls. Finally, ICI treatment of both PDOs/PDTXs demonstrated cytotoxicity and anti-MEK1/2 combined with anti-PD-1 drugs produced highest cytotoxicity in PDOs/PDTXs. CONCLUSIONS: Our data reveal PCs innately express PD-1 and activate druggable oncogenic pathways supporting PDAC growth. Strategies directly targeting PC with novel ICI regimens may work with adaptive immune responses for optimal cytotoxicity.
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Antígeno B7-H1/imunologia , Imunoterapia , Neoplasias Pancreáticas/tratamento farmacológico , Receptor de Morte Celular Programada 1/imunologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Organoides/efeitos dos fármacos , Organoides/imunologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Cultura Primária de Células , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The Kuramoto model with mixed signs of couplings is known to produce a traveling-wave synchronized state. Here, we consider an abrupt synchronization transition from the incoherent state to the traveling-wave state through a long-lasting metastable state with large fluctuations. Our explanation of the metastability is that the dynamic flow remains within a limited region of phase space and circulates through a few active states bounded by saddle and stable fixed points. This complex flow generates a long-lasting critical behavior, a signature of a hybrid phase transition. We show that the long-lasting period can be controlled by varying the density of inhibitory/excitatory interactions. We discuss a potential application of this transition behavior to the recovery process of human consciousness.
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The goal of this study was to characterize the relationship between tumor uptake of 64Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods: Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including 18F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent 64Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h after 64Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUVmax Average intrapatient SUVmax (
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Anticorpos Monoclonais Humanizados/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Compostos Organometálicos/metabolismo , Adulto , Idoso , Transporte Biológico , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2/metabolismo , TrastuzumabRESUMO
The Hopfield model is a pioneering neural network model with associative memory retrieval. The analytical solution of the model in mean field limit revealed that memories can be retrieved without any error up to a finite storage capacity of O(N), where N is the system size. Beyond the threshold, they are completely lost. Since the introduction of the Hopfield model, the theory of neural networks has been further developed toward realistic neural networks using analog neurons, spiking neurons, etc. Nevertheless, those advances are based on fully connected networks, which are inconsistent with recent experimental discovery that the number of connections of each neuron seems to be heterogeneous, following a heavy-tailed distribution. Motivated by this observation, we consider the Hopfield model on scale-free networks and obtain a different pattern of associative memory retrieval from that obtained on the fully connected network: the storage capacity becomes tremendously enhanced but with some error in the memory retrieval, which appears as the heterogeneity of the connections is increased. Moreover, the error rates are also obtained on several real neural networks and are indeed similar to that on scale-free model networks.