The US Food and Drug Administration (FDA) approved the first oncolytic viral therapy (OVT), Imlygic (talimogene laherparepvec), in October 2015 for the local treatment of unresectable cutaneous, ...subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery, although talimogene has not been shown to improve overall survival or have an effect on visceral metastases.
In this study, a novel vibration isolator is developed. The developed isolator possesses the characteristics of high-static–low-dynamic stiffness (HSLDS) and can act passively or semi-actively. The ...HSLDS property of the isolator is obtained by connecting a mechanical spring, in parallel with a magnetic spring that is constructed by a pair of electromagnets and a permanent magnet. The mechanical spring is a structural beam whose stiffness exhibits a hardening behavior. The stiffness of the magnetic spring can be positive or negative, depending on the polarity of the current to the electromagnets. A passive HSLDS isolator is obtained when the electromagnet current is zero. In the stiffness characterization study, the analytical model for each of the springs is established and the tuning parameters are identified. Using the stiffness models, the design optimization issues are investigated. In the experimental study, the effectiveness of the isolator for vibration isolation is tested. The analytical natural frequencies of the isolator are validated experimentally. The relationships between the displacement transmissibility and the exciting frequency are measured both under the passive mode and under the semi-active mode. The on-line tuning capability of the isolator is investigated.
A central goal in sensory neuroscience is to understand the neuronal signal processing involved in the encoding of natural stimuli. A critical step towards this goal is the development of successful ...computational encoding models. For ganglion cells in the vertebrate retina, the development of satisfactory models for responses to natural visual scenes is an ongoing challenge. Standard models typically apply linear integration of visual stimuli over space, yet many ganglion cells are known to show nonlinear spatial integration, in particular when stimulated with contrast-reversing gratings. We here study the influence of spatial nonlinearities in the encoding of natural images by ganglion cells, using multielectrode-array recordings from isolated salamander and mouse retinas. We assess how responses to natural images depend on first- and second-order statistics of spatial patterns inside the receptive field. This leads us to a simple extension of current standard ganglion cell models. We show that taking not only the weighted average of light intensity inside the receptive field into account but also its variance over space can partly account for nonlinear integration and substantially improve response predictions of responses to novel images. For salamander ganglion cells, we find that response predictions for cell classes with large receptive fields profit most from including spatial contrast information. Finally, we demonstrate how this model framework can be used to assess the spatial scale of nonlinear integration. Our results underscore that nonlinear spatial stimulus integration translates to stimulation with natural images. Furthermore, the introduced model framework provides a simple, yet powerful extension of standard models and may serve as a benchmark for the development of more detailed models of the nonlinear structure of receptive fields.
Investigation of rock progressive damage under static confinement and strain rates facilitates the generation mechanism of natural fault damage zones. A triaxial Hopkinson bar apparatus is used to ...perform dynamic triaxial compression tests to examine the damage and degradation process of rocks subjected to multiple impacts. Dynamic mechanical properties are determined under a static triaxial pre-stress of (30, 20, 10) MPa and multiple dynamic loadings, with the repetitive impact velocity of 27 m/s and strain rates from 50 to 150/s. The acoustic characteristics are identified by ultrasonic measurement to qualify the damage values. The micro-crack parameters, including crack area and volumes are detected using synchrotron X-ray micro-computed tomography (μCT) to characterize the progressive damage. In addition, the microcrack orientation, density and fractal dimension are analysed from thin section. Experimental results show that dynamic stress-strain curves can be divided to elastic, nonlinear deformation and unloading phases. Dynamic peak stress, Young’s modulus and ultrasonic wave velocity decrease with increasing impact times. The high frequency of ultrasonic wave is filtered by the induced microcracks. The progressive damage and evolution of fracture networks are associated highly with microcrack initiation, propagation, branching and coalescence. Shear bands are commonly generated in granite, and tensile cracks are dominant in marble, while sandstone is mainly failed by compaction and deformation band. The absorbed energy of rock increases nonlinearly with increasing crack surface and volume. Besides, microcracks propagate primarily along the maximum principal stress; the density and fractal dimension exhibit an anisotropic distribution controlled by true triaxial confinement and dynamic impacts.
Plastic film mulching has played an important role in Chinese agriculture due to its soil warming and moisture conservation effects. With the help of plastic film mulch technology, grain and cash ...crop yields have increased by 20-35% and 20-60%, respectively. The area of plastic film coverage in China reached approximately 20 million hectares, and the amount of plastic film used reached 1.25 million tons in 2011. While producing huge benefits, plastic film mulch technology has also brought on a series of pollution hazards. Large amounts of residual plastic film have detrimental effects on soil structure, water and nutrient transport and crop growth, thereby disrupting the agricultural environment and reducing crop production. To control pollution, the Chinese government urgently needs to elevate plastic film standards. Meanwhile, research and development of biodegradable mulch film and multi-functional mulch recovery machinery will help promote effective control and management of residual mulch pollution.
In recent decades, we have witnessed the evolution of information technologies from the development of VLSI technologies, to communication and networking infrastructure, to the standardization of ...multimedia compression and coding schemes, to effective multimedia content search and retrieval. As a result, multimedia devices and digital content have become ubiquitous. This path of technological evolution has naturally led to a critical issue that must be addressed next, namely, to ensure that content, devices, and intellectual property are being used by authorized users for legitimate purposes, and to be able to forensically prove with high confidence when otherwise. When security is compromised, intellectual rights are violated, or authenticity is forged, forensic methodologies and tools are employed to reconstruct what has happened to digital content in order to answer who has done what, when, where, and how. The goal of this paper is to provide an overview on what has been done over the last decade in the new and emerging field of information forensics regarding theories, methodologies, state-of-the-art techniques, major applications, and to provide an outlook of the future.
Background
Patients undergoing major non‐cardiac surgery are at risk of cardiovascular complications. Raised levels of high‐sensitivity troponin are frequently detected before operation among these ...patients. However, the prognostic value of high‐sensitivity troponin in predicting postoperative outcomes remains unclear.
Methods
A systematic search of PubMed, Embase and Science Citation Index Expanded was undertaken for observational studies published before March 2018 that reported associations between raised preoperative levels of high‐sensitivity troponin and postoperative major adverse cardiac events and/or mortality after non‐cardiac surgery. Meta‐analyses were performed, where possible, using random‐effects models.
Results
Seven cohort studies with a total of 4836 patients were included. A raised preoperative high‐sensitivity troponin level was associated with a higher risk of short‐term major adverse cardiac events (risk ratio (RR) 2·92, 95 per cent c.i. 1·96 to 4·37; I2 = 82·6 per cent), short‐term mortality (RR 5·39, 3·21 to 9·06; I2 = 0 per cent) and long‐term mortality (RR 2·90, 1·83 to 4·59, I2 = 74·2 per cent). The addition of preoperative high‐sensitivity troponin measurement provided improvements in cardiovascular risk discrimination (increase in C‐index ranged from 0·058 to 0·109) and classification (quantified by continuous net reclassification improvement) compared with Lee's Revised Cardiac Risk Index alone. There was substantial heterogeneity and inadequate risk stratification analysis in the included studies.
Conclusion
Raised preoperative levels of high‐sensitivity troponin appear to represent a risk for postoperative major adverse cardiac events and mortality. Further study is required before high‐sensitivity troponin can be used to predict risk stratification in routine clinical practice.
Antecedentes
Los pacientes a los que se realiza una cirugía mayor no cardíaca tienen riesgo de presentar complicaciones cardiovasculares. En estos pacientes se observan con frecuencia niveles preoperatorios elevados de troponina de alta sensibilidad (high‐sensitivity troponin, hs‐cTn). Sin embargo, el valor pronóstico de la hs‐cTn para predecir los resultados postoperatorios no está bien definido.
Métodos
Se realizó una búsqueda sistemática en las bases de datos PubMed, EMBASE y Science Citation Index Expanded de estudios observacionales publicados antes de marzo de 2018 que analizasen la posible relación de los niveles elevados preoperatorios de hs‐cTn y los efectos adversos graves de tipo cardíaco (major adverse cardiac events, MACE) postoperatorios y/o la mortalidad después de la cirugía no cardíaca. Se realizó el metaanálisis utilizando modelos de efectos aleatorios siempre que fuera posible.
Resultados
Se incluyeron siete estudios de cohortes con un total de 4.836 pacientes. La elevación preoperatoria de hs‐cTn se asoció con un mayor riesgo de MACE a corto plazo (tasa de riesgo, risk ratio, RR 2,92, i.c. del 95% 1,96‐4,37, I2 = 82,6%) y con la mortalidad a corto plazo (RR 5,39, i.c. del 95 % 3,21‐9,06, I2 = 0%) y a largo plazo (RR 2,90, i.c. del 95% 1,83‐4,59, I2 = 74,2%). Añadir la medición preoperatoria de hs‐cTn mejoró la capacidad discriminativa para el riesgo cardiovascular (aumento de 5,8% a 10,9% en el índice C) y también la clasificación de los pacientes (cuantificada mediante el índice de reclasificación neta continua) en comparación con el uso de solo el índice de riesgo cardíaco revisado de Lee. En los estudios incluidos, hubo gran heterogeneidad y análisis inadecuado de la estratificación del riesgo.
Conclusión
Los niveles preoperatorios elevados de troponina de alta sensibilidad parecen ser un marcador de riesgo de efectos adversos graves de tipo cardíaco en el postoperatorio y de mortalidad. Se requieren más estudios antes de utilizar la troponina de alta sensibilidad para la estratificación del riesgo en la práctica clínica rutinaria.
This systematic review and meta‐analysis explored the prognostic implication of preoperative high‐sensitivity cardiac troponin (hs‐cTn) level in patients undergoing non‐cardiac surgery who are at risk of cardiovascular complications. An increase in preoperative hs‐cTn level was identified as a risk marker for postoperative major adverse cardiac events (MACE) and death. Further study is required before hs‐cTn assays could be used for routine preoperative risk stratification.
High‐sensitivity cardiac troponin appears useful
Gastroesophageal adenocarcinomas (GEAs) are heterogeneous cancers where immune checkpoint inhibitors have robust efficacy in heavily inflamed microsatellite instability (MSI) or Epstein-Barr virus ...(EBV)-positive subtypes. Immune checkpoint inhibitor responses are markedly lower in diffuse/genome stable (GS) and chromosomal instable (CIN) GEAs. In contrast to EBV and MSI subtypes, the tumor microenvironment of CIN and GS GEAs have not been fully characterized to date, which limits our ability to improve immunotherapeutic strategies.
Here we aimed to identify tumor-immune cell association across GEA subclasses using data from The Cancer Genome Atlas (N = 453 GEAs) and archival GEA resection specimen (N = 71). The Cancer Genome Atlas RNAseq data were used for computational inferences of immune cell subsets, which were correlated to tumor characteristics within and between subtypes. Archival tissues were used for more spatial immune characterization spanning immunohistochemistry and mRNA expression analyses.
Our results confirmed substantial heterogeneity in the tumor microenvironment between distinct subtypes. While MSI-high and EBV+ GEAs harbored most intense T cell infiltrates, the GS group showed enrichment of CD4+ T cells, macrophages and B cells and, in ∼50% of cases, evidence for tertiary lymphoid structures. In contrast, CIN cancers possessed CD8+ T cells predominantly at the invasive margin while tumor-associated macrophages showed tumor infiltrating capacity. Relatively T cell-rich ‘hot’ CIN GEAs were often from Western patients, while immunological ‘cold’ CIN GEAs showed enrichment of MYC and cell cycle pathways, including amplification of CCNE1.
These results reveal the diversity of immune phenotypes of GEA. Half of GS gastric cancers have tertiary lymphoid structures and are therefore promising candidates for immunotherapy. The majority of CIN GEAs, however, exhibit T cell exclusion and infiltrating macrophages. Associations of immune-poor CIN GEAs with MYC activity and CCNE1 amplification may enable new studies to determine precise mechanisms of immune evasion, ultimately inspiring new therapeutic modalities.
•There is large heterogeneity in the immune contexture of gastroesophageal adenocarcinoma (GEA) subtypes.•Chromosomal instable GEAs are often T cell excluded, which is associated with enhanced MYC and cell cycle pathways.•Genome stable cancers, contrarily, often have tertiary lymphoid structures.•This study argues for more personalized immunotargeting strategies in gastroesophageal cancer treatment.
Dynamic spectrum access in cognitive radio networks can greatly improve the spectrum utilization efficiency. Nevertheless, interference may be introduced to the Primary User (PU) when the Secondary ...Users (SUs) dynamically utilize the PU's licensed channels. If the SUs can be synchronous with the PU's time slots, the interference is mainly due to their imperfect spectrum sensing of the primary channel. However, if the SUs have no knowledge about the PU's exact communication mechanism, additional interference may occur. In this paper, we propose a dynamic spectrum access protocol for the SUs confronting with unknown primary behavior and study the interference caused by their dynamic access. Through analyzing the SUs' dynamic behavior in the primary channel which is modeled as an ON-OFF process, we prove that the SUs' communication behavior is a renewal process. Based on the Renewal Theory, we quantify the interference caused by the SUs and derive the corresponding closed-form expressions. With the interference analysis, we study how to optimize the SUs' performance under the constraints of the PU's communication quality of service (QoS) and the secondary network's stability. Finally, simulation results are shown to verify the effectiveness of our analysis.
In this paper, a novel cognitive multiple-access strategy in the presence of a cooperating relay is proposed. Exploiting an important phenomenon in wireless networks, source burstiness, the cognitive ...relay utilizes the periods of silence of the terminals to enable cooperation. Therefore, no extra channel resources are allocated for cooperation and the system encounters no bandwidth losses. Two protocols are developed to implement the proposed multiple-access strategy. The maximum stable throughput region and the delay performance of the proposed protocols are characterized. The results reveal that the proposed protocols provide significant performance gains over conventional relaying strategies such as selection and incremental relaying, specially at high spectral efficiency regimes. The rationale is that the lossless bandwidth property of the proposed protocols results in a graceful degradation in the maximum stable throughput with increasing the required rate of communication. On the other hand, conventional relaying strategies suffer from catastrophic performance degradation because of their inherent bandwidth inefficiency that results from allocating specific channel resources for cooperation at the relay. The analysis reveals that the throughput region of the proposed strategy is a subset of its maximum stable throughput region, which is different from random access, where both regions are conjectured to be identical.
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