An unexplored gap in IT adoption research concerns the positive role of shared benefits even when personal information is exposed. To explore the evaluation paradigm of shared benefits versus the ...forfeiture of personal information, we analyze how utility consumers use smart metering technology (SMT). In this context, utility companies can monitor electricity usage and directly control consumers' appliances to disable them during peak load conditions. Such information could reveal consumers' habits and lifestyles and, thus, stimulating concerns about their privacy and the loss of control over their appliances. Responding to calls for theory contextualization, we assess the efficacy of applying extant adoption theories in this emergent context while adding the perspective of the psychological ownership of information. We use the factorial survey method to assess consumers' intentions to adopt SMT in the presence of specific conditions that could reduce the degree of their privacy or their control over their appliances and electricity usage data. Our findings suggest that, although the shared benefit of avoiding disruptions in electricity supply (brownouts) is a significant factor in electricity consumers' decisions to adopt SMT, concerns about control and information privacy are also factors. Our findings extend the previous adoption research by exploring the role of shared benefits and could provide utility companies with insights into the best ways to present SMT to alleviate consumers' concerns and maximize its adoption.
Patterns of Response and Progression to Immunotherapy Borcoman, Edith; Nandikolla, Amara; Long, Georgina ...
American Society of Clinical Oncology educational book,
05/2018, Letnik:
38, Številka:
38
Journal Article
Recenzirano
Patterns of response and progression to immunotherapy may differ from those observed with drugs such as chemotherapy and molecularly targeted agents. Specifically, some patients experience a response ...after progression that is retrospectively named pseudoprogression. This phenomenon of pseudoprogression, first reported in patients with melanoma who were treated with ipilimumab, has led to the development of immune-specific related response criteria, such as irRC (immune-related response criteria), irRECIST (immune-related RECIST), and iRECIST (immunotherapy RECIST) that allow continued treatment beyond progression. However, the rate of pseudoprogression has never exceeded 10% of patients across tumor types. Conversely, rapid progressions after immunotherapy, called hyperprogressions, were reported by three different teams in 9% to 29% of patients treated with immunotherapy. Because of the absence of control arms in these studies, it remains to be determined whether these rapid progressions reflect a detrimental effect of immunotherapy in these patients. Finally, preliminary data suggest that immunotherapy might also affect response to subsequent standard therapies. In total, given the rarity of pseudoprogressions across tumor types and the recent description of hyperprogressions, classic RECIST remains a reasonable and rational method to assess response to immunotherapy. Continuation of treatment beyond progression should be proposed only in carefully selected patients whose clinical conditions have improved and who have not experienced severe toxicities. Although there is an urgent need to identify predictive biomarkers of efficacy to immunotherapy, there is an equally urgent need to identify predictive factors of progression or possibly hyperprogression.
The purpose of the investigation was to study the effect of binary and ternary blends of cement on the mechanical properties of pervious concrete (PC) specimen through destructive (DT) and ...non-destructive testing (NDT). Various combinations of fly ash (FA), limestone powder (LP), metakaolin (MK), and silica fume (SF) as mineral admixtures have been investigated to partially replace the cement up to 30% by weight in PC. Standard cube specimens of size 150 mm × 150 mm × 150 mm of binary and ternary blends of mineral admixture of pervious concrete were prepared to conduct standard compressive strength test and split tensile test at 7 and 28 days of curing. The ultrasonic pulse velocity (UPV) test and Rebound Hammer test were used as a non-destructive testing tool to substantiate the robustness of PC and to determine the approximate mechanical properties where other destructive testing tools are not feasible in case of in-place pervious pavements. Overall the pervious concrete made with LP based ternary blends (PLM and PLS) were found to perform better than FA based ternary blends (PFM and PFS) and control mix (PC) in destructive and non-destructive testing.
CPT-11 (irinotecan), a DNA topoisomerase I inhibitor is one of the main treatments for colorectal cancer. The main dose limiting toxicities are neutropenia and late onset diarrhea. Though neutropenia ...is manageable, CPT-11 induced diarrhea is frequently severe, resulting in hospitalizations, dose reductions or omissions leading to ineffective treatment administration. Many potential agents have been tested in preclinical and clinical studies to prevent or ameliorate CPT-11 induced late onset diarrhea. It is predicted that prophylaxis of CPT-11 induced diarrhea will reduce sub-therapeutic dosing as well as hospitalizations and will eventually lead to dose escalations resulting in better response rates. This article reviews various experimental agents and strategies employed to prevent this debilitating toxicity. Covered topics include schedule/dose modification, intestinal alkalization, structural/chemical modification, genetic testing, anti-diarrheal therapies, transporter (ABCB1, ABCC2, BCRP2) inhibitors, enzyme (β-glucuronidase, UGT1A1, CYP3A4, carboxylesterase, COX-2) inducers and inhibitors, probiotics, antibiotics, adsorbing agents, cytokine and growth factor activators and inhibitors and other miscellaneous agents.
Eribulin in Cancer Treatment Swami, Umang; Shah, Umang; Goel, Sanjay
Marine Drugs,
08/2015, Letnik:
13, Številka:
8
Journal Article, Book Review
Recenzirano
Odprti dostop
Halichondrin B is a complex, natural, polyether macrolide derived from marine sponges. Eribulin is a structurally-simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. Eribulin was ...approved by United States Food and Drug Administration in 2010 as a third-line therapy for metastatic breast cancer patients who have previously been treated with an anthracycline and a taxane. It has a unique microtubule dynamics inhibitory action. Phase III studies have either been completed or are currently ongoing in breast cancer, soft tissue sarcoma, and non-small cell lung cancer. Phase I and II studies in multiple cancers and various combinations are currently ongoing. This article reviews the available information on eribulin with respect to its clinical pharmacology, pharmacokinetics, pharmacodynamics, mechanism of action, metabolism, preclinical studies, and with special focus on clinical trials.
In this paper, we conceptually and empirically investigate the relationship between industry and information security awareness (ISA). Different industries have unique security related norms, rules, ...and values, which we propose promotes different levels of organizational effort to raise their employees’ general ISA. To examine these potential industry effects, we draw on Neo-Institutional Theory (NIT) because different industries operate in unique institutional environments. We specifically theorize that the pressures from the three institutional pillars (regulative, normative, and cultural-cognitive) will affect employees across all industries but the magnitude of those effects will vary across industries, because different industries have institutionalized security practices in unique ways. To evaluate our theorized relationships empirically, we surveyed employees in the banking, healthcare, retail, and higher education industries. We found that our subjects’ perceptions of the pressures from the three institutional pillars positively affected their perceptions of how much effort their organizations exerted to raise their general ISA. However, we also found that these effects were not consistent across our surveyed employees in the different industries, especially related to the direct and moderating effect of perceived normative institutional pressures. The implication of our paper is that future behavioral information security research should consider how industry and their corresponding institutional structures might affect (positively or negatively) the relationships in our core theoretical models.
KRAS mutations are prevalent in 40-45% of patients with colorectal cancer (CRC) and targeting this gene has remained elusive. Viruses are well known immune sensitizing agents. The therapeutic ...efficacy of oncolytic reovirus in combination with chemotherapy is examined in a phase 1 study of metastatic CRC. This study evaluates the nature of immune response by determining the cytokine expression pattern in peripheral circulation along with the distribution of antigen presenting cells (APCs) and activated T lymphocytes. Further the study evaluates the alterations in exosomal and cellular microRNA levels along with the effect of reovirus on leukocyte transcriptome.
Reovirus was administered as a 60-min intravenous infusion for 5 consecutive days every 28 days, at a tissue culture infective dose (TCID
) of 3 × 10
. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood prior to reovirus administration and post-reovirus on days 2, 8, and 15. The expression profile of 25 cytokines in plasma was assessed (post PBMC isolation) on an EMD Millipore multiplex Luminex platform. Exosome and cellular levels of miR-29a-3p was determined in pre and post reovirus treated samples. Peripheral blood mononuclear cells were stained with fluorophore labelled antibodies against CD4, CD8, CD56, CD70, and CD123, fixed and evaluated by flow cytometry. The expression of granzyme B was determined on core biopsy of one patient. Finally, Clariom D Assay was used to determine the expression of 847 immune-related genes when compared to pre reovirus treatment by RNA sequencing analysis. A change was considered if the expression level either doubled or halved and the significance was determined at a p value of 0.001.
Cytokine assay indicated upregulation at day 8 for IL-12p40 (2.95; p = 0.05); day 15 for GM-CSF (3.56; p = 0.009), IFN-y (1.86; p = 0.0004) and IL-12p70 (2.42; p = 0.02). An overall reduction in IL-8, VEGF and RANTES/CCL5 was observed over the 15-day period. Statistically significant reductions were observed at Day 15 for IL-8 (0.457-fold, 53.3% reduction; p = 0.03) and RANTES/CC5 (0.524-fold, 47.6% reduction; p = 0.003). An overall increase in IL-6 was observed, with statistical significance at day 8 (1.98- fold; 98% increase, p = 0.00007). APCs were stimulated within 48 h and activated (CD8
CD70
) T cells within 168 h as determine by flow cytometry. Sustained reductions in exosomal and cellular levels of miR-29a-3p (a microRNA upregulated in CRC and associated with decreased expression of the tumor suppressor WWOX gene) was documented. Reovirus administration further resulted in increases in KRAS (33x), IFNAR1 (20x), STAT3(5x), and TAP1 (4x) genes after 2 days; FGCR2A (23x) and CD244 (3x) after 8 days; KLRD1 (14x), TAP1 (2x) and CD244(2x) after 15 days. Reductions (> 0.5x) were observed in VEGFA (2x) after 2 days; CXCR2 (2x), ITGAM (3x) after 15 days.
Reovirus has profound immunomodulatory properties that span the genomic, protein and immune cell distribution levels. This is the first study with reovirus in cancer patients that demonstrates these multi- layered effects, demonstrating how reovirus can function as an immune stimulant (augmenting the efficacy of immuno-chemo-therapeutic drugs), and an oncolytic agent. Reovirus thus functions bimodally as an oncolytic agent causing lysis of tumor cells, and facilitator of immune-mediated recognition and destruction of tumor cells.
The objective of this paper is to articulate the problem of attribution in cyber warfare incidents, including, surveillance, data theft, espionage, and misinformation campaigns. As the stakes ...increase, concerted efforts are being made by intelligence and law enforcement agencies to identify the perpetrators with much painstaking effort. Attribution tools and techniques for malicious activities on the Internet are still nascent, relying mainly on technical measurements, the provenance of malicious code, and non-technical assessments of attack and attacker characteristics to link attack activities to individuals or groups. Attribution of attacks is typically done through a burdensome manual process that relies on both technical analysis and ground intelligence. As a result, this cumbersome and laborious process of attribution is primarily reserved for the most egregious cyber attack cases and those conducted against well resourced organizations. Over time, our attribution abilities have improved, however, this improvement is a two-edged sword: as attribution capabilities improve, Internet privacy is increasingly diluted. This paper discusses attribution for two vastly different types of attacks that are central to cyber conflict today: network intrusions and social bot-led misinformation campaigns. The paper discusses the state of the art regarding attribution abilities across both types of attack, provides recommendations for improved attribution, and lays out future research directions.
The KRAS gene is mutated in approximately 45% of colorectal cancer patients. There are currently very few targeted treatments or therapies equipped to directly inhibit KRAS due to its unusual ...structural intricacies. Erlotinib, an EGFR inhibitor, has previously been demonstrated to reduce cell viability by inducing autophagy in lung cancer cell lines with varying EGFR mutations. In contrast to lung cancer cells, evidence is provided herein for the first time that erlotinib treatment in colorectal cancer (CRC) cell lines reduces autophagy and still results in decreased cell viability. However, the effects of erlotinib in CRC cell lines containing a wildtype KRAS gene were different than in cells carrying a mutant KRAS gene. We show that there is significantly more downregulation of autophagy in KRAS mutant CRC cells compared to KRAS wildtype cells, both at transcriptional and translational levels, suggesting that the KRAS mutation is advantageous for cancer growth, even in the presence of erlotinib. Cell viability results determined that KRAS wildtype CRC cells had significantly more cell death compared to KRAS mutant cells. Using patient mRNA datasets, we showed that there was a significant correlation between the presence of the KRAS mutation and the expression of autophagy proteins. Additionally, through molecular dynamics simulations, we develop a blueprint for KRAS and autophagy protein interaction and the impact of the KRAS mutation on autophagy protein regulation. Overall, this is the first report of erlotinib treatment in CRC cells that assesses autophagy, and we demonstrate that autophagy activity is downregulated in these cells. This effect is not only greater in cells carrying a KRAS mutation compared to wildtype cells, but the KRAS mutant cells also have increased cell viability compared to wildtype cells. We hypothesize that the difference in cell viability and autophagy expression between KRAS mutant and KRAS wildtype cells after treatment with erlotinib can be of therapeutic value to treat CRC patients carrying KRAS mutations.
Intrusion detection systems utilize the analysis of log data to effectively detect anomalies. However, detecting anomalies quickly and effectively in large and heterogeneous log data can be ...challenging. To address this difficulty, this study proposes the GLSTM (Graph-based Long Short-Term Memory) framework, a graph-based deep learning model that analyzes log data to detect cyber-attacks rapidly and effectively. The framework involves standardizing the complex and diverse log data, training this data on an artificial intelligence model, and detecting anomalies. Initially, the complex and diverse log data is transformed into graph data using Node2Vec, enabling efficient and rapid analysis on the artificial intelligence model. Subsequently, these graph data are trained using LSTM (Long Short-Term Memory), Bi-LSTM, and GRU(Gated Recurrent Unit) deep learning algorithms. The proposed framework is tested using Hadoop’s HDFS dataset, collected from different systems and heterogeneous sources, as well as the BGL and IMDB datasets. Experimental results on the selected datasets demonstrate high levels of success.
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