RESUMO
Transportation networks play a crucial role in human and animal societies. For a transportation network to be efficient, it must have adequate capacity to meet traffic demand. Network design becomes increasingly difficult in situations where traffic demand can change unexpectedly. In humans, network design is often constrained by path dependency because it is difficult to move a road once it is built. A similar issue theoretically faces pheromone-trail-laying social insects; once a trail has been laid, positive feedback makes re-routing difficult because new trails cannot compete with continually reinforced pre-existing trails. In the present study, we examined the response of Argentine ant colonies and their trail networks to variable environments where resources differ in quality and change unexpectedly. We found that Argentine ant colonies effectively tracked changes in food quality such that colonies allocated the highest proportion of foragers to the most rewarding feeder. Ant colonies maximised access to high concentration feeders by building additional trails and routes connecting the nest to the feeder. Trail networks appeared to form via a pruning process in which lower traffic trails were gradually removed from the network. At the same time, we observed several instances where new trails appear to have been built to accommodate a surge in demand. The combination of trail building when traffic demand is high and trail pruning when traffic demand is low results in a demand-driven network formation system that allows ants to monopolise multiple dynamic resources.
Assuntos
Formigas/fisiologia , Comportamento Apetitivo , Animais , Comportamento Alimentar , Feromônios/metabolismoRESUMO
The ability to noninvasively diagnose acute cellular rejection (ACR) with high specificity and sensitivity would significantly advance personalized liver transplant recipient care and management of immunosuppression. We performed microRNA (miRNA) profiling in 318 serum samples from 69 liver transplant recipients enrolled in the Immune Tolerance Network immunosuppression withdrawal (ITN030ST) and Clinical Trials in Organ Transplantation (CTOT-03) studies. We quantified serum miRNA at clinically indicated and/or protocol biopsy events (n = 130). The trajectory of ACR diagnostic miRNAs during immunosuppression withdrawal were also evaluated in sera taken at predetermined intervals during immunosuppression minimization before and at clinically indicated liver biopsy (n = 119). Levels of 31 miRNAs were significantly associated with ACR diagnosis with two miRNAs differentiating ACR from non-ACR (area under the receiver operating characteristic curve = 90%, 95% confidence interval = 82%-96%) and predicted ACR events up to 40 days before biopsy-proven rejection. The most differentially expressed miRNAs were low or absent in the blood of healthy individuals but highly expressed in liver tissue, indicating an ectopic origin from the liver allograft. Pathway analyses of rejection-associated miRNAs and their target messenger RNAs (mRNAs) showed induction of proinflammatory and cell death-related pathways. Integration of differentially expressed serum miRNA with concordant liver biopsy mRNA demonstrates interaction between molecules with a known role in transplant rejection. CONCLUSION: Distinct miRNA levels profiled from sera at the time of clinical allograft dysfunction can be used to noninvasively diagnose ACR. Predictive trajectories of the same profile during supervised immunosuppression minimization diagnosed rejection up to 40 days prior to clinical expression. The rejection-associated miRNAs in sera appear to be ectopically expressed liver and specific immune cell miRNAs that are biologically related, and the consequences of immune-mediated damage to the allograft. (Hepatology 2017;65:269-280).
Assuntos
Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Transplante de Fígado , MicroRNAs/sangue , Expressão Ectópica do Gene , Feminino , Rejeição de Enxerto/genética , Humanos , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Transcriptoma , Transplante HomólogoRESUMO
BACKGROUND: Despite existing guidelines for first-line treatment of metastatic renal cell carcinoma (mRCC), prescribing preferences in the United States have not been fully examined. The objectives of this study were to characterize US physicians' preferences and factors influencing first-line mRCC treatment. MATERIALS AND METHODS: A Web-based study presented physicians with hypothetical mRCC patient cases and recorded initial therapy preference and rationale. Descriptive statistics were used to characterize preferred treatment; logistic regression was used to determine patient characteristics associated with therapy changes. Analyses were conducted on pooled responses across cases. Model results were summarized using odds ratios (ORs), 95% confidence intervals, and P values for the covariates. RESULTS: One hundred nine physicians participated in the study; 96 (88.1%) chose a tyrosine kinase inhibitor as their preferred first-line mRCC treatment (62 [56.9%], sunitinib; 31 [28.4%], pazopanib). Perceived superior overall survival and progression-free survival were top reasons physicians chose sunitinib; enhanced tolerability and efficacy similar to sunitinib were top reasons physicians chose pazopanib. Initial sunitinib prescribers were more likely to change therapy in the presence of comorbid conditions (OR, 2.915; P = .0068), poor Eastern Cooperative Oncology Group performance status (OR, 2.368; P = .0106), or poor prognostic risk (OR, 3.884; P = .0224). This was not seen for initial pazopanib prescribers. CONCLUSION: Sunitinib and pazopanib were the most preferred agents for first-line mRCC treatment. Sunitinib preference was driven by perceptions of efficacy, and pazopanib was preferred for its perceived tolerability and efficacy similar to sunitinib. With varying clinical scenarios, initial pazopanib prescribers were more likely to maintain pazopanib and alter dosing; sunitinib prescribers were more likely to switch therapy.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Feminino , Humanos , Indazóis , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Sunitinibe , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVES: Performance improvement programs in emergency medicine (EM) have evolved beyond peer reviews of referred cases and now encompass a large set of quality metrics that are measured proactively. However, peer review of cases continues to be an important element of performance improvement, and selection of cases tends to be driven by an ad hoc referral process based on concerns about problems with care in the emergency department (ED). In the past decade, there has been widespread hospital adoption of rapid response teams (RRTs) that respond to patients who decline clinically to reduce adverse outcomes. In an effort to cast a wider net, to take a more systematic approach, and to avoid "blind spots" from individual variability in criteria for referring cases, the institution instituted a new process for selecting cases for ED peer review based on RRT activations within 24 hours of admission from the ED. The hypothesis was that a formal process for review of these activation cases would increase the number of cases for peer review. METHODS: This was a prospective, observational study conducted from July 1, 2012, to June 30, 2013, at an urban, academic medical center with an EM residency program. A new automated monthly report was created, capturing all RRT activations within 24 hours of admission from the ED. All events were reviewed by three physicians from the ED performance improvement committee to examine for systems issues, individual provider issues, or both, that might yield opportunities for improvement. Cases with potential opportunities were reviewed by the full ED performance improvement committee. Cases were classified according to the indication for response team activation using the system outlined by the U.S. Agency for Healthcare Research and Quality. RESULTS: During the study period 61,814 patients were treated in the ED, and 13,067 were admitted to inpatient status. Thirty-two RRT activations within 24 hours of admission from the ED occurred among these admitted patients, representing 0.24% of admissions (95% confidence interval [CI] = 0.16% to 0.33%). Of the 32 cases, only one was also referred independently for ED performance improvement review via the traditional ad hoc process. During the same period of time, 85 cases were referred to the ED performance improvement committee via the traditional ad hoc referral process. Thus, the RRT cases added an additional 31 cases, or 36.5%, to the 85 cases reviewed in ED performance improvement. Of the 32 cases, two were determined by the performance improvement committee to have individual provider factors in their ED care, which contributed to the clinical decline triggering the response teams; none had system factors. Most of the response team activations were for neurologic changes (n = 13) and respiratory status changes (n = 12). In two cases there was long-term morbidity or mortality related to the team activation event; in neither of these cases were ED system or individual provider factors judged to have contributed. CONCLUSIONS: The review of RRT activations within 24 hours of admission from the ED significantly supplemented the typical ad hoc referral system for peer review of cases, highlighting cases that likely would not have received attention within the ED. This novel and unique case review process revealed opportunities for education and performance improvement. This and other systematic approaches to case detection may be useful adjuncts to traditional case referrals for review.