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PurposeThe purpose of this research is the exploration of online complainants' revenge based on their consumer-brand relationship strength and received webcare. The authors introduce inter-failures (i.e. the perceived number of earlier independent service failures that a customer has experienced with the same brand involved in the current service failure) as the central frame condition.Design/methodology/approachTo test our hypotheses, both a scenario-based online experiment (n = 316) and an online survey (n = 492) were conducted.FindingsWith an increasing number of inter-failures, online complainants with a high-relationship strength move from the “love is blind” effect (no inter-failures) to the “love becomes hate” effect (multiple inter-failures), when they ultimately become more revengeful than their low-relationship strength counterparts. In addition, the authors show that in the case of no or few inter-failures, accommodative webcare has a lasting positive effect over no/defensive webcare for both low- and high-relationship complainants. More importantly, however, when consumers have experienced multiple inter-failures, accommodative webcare becomes ineffective (for low-relationship complainants) or boomerangs by cultivating revenge towards the brand (among high-relationship complainants), but not strategic avoidance.Research limitations/implicationsThe findings have pronounced implications for the literature on customer–brand relationships following service failures and the literature, which predominantly emphasizes the unconditionally positive effects of accommodative webcare.Originality/valueThis study is the first that simultaneously considers the prior customer–brand relationship, inter-failures and webcare to explain online complainants' revenge.

Nanoparticles (NPs) and other engineered nanomaterials have great potential as nanodrugs or nanomedical devices for biomedical applications. However, the adsorption of proteins in blood circulation or similar physiological fluids can significantly alter the surface properties and therapeutic response induced by most nanomaterials. For example, interaction with proteins can change the bloodstream circulation time and availability of therapeutic NPs or hinder the accumulation in their desired target organs. Proteins can also trigger or prevent agglomeration. By combining experimental and computational approaches, we have developed NPs carrying polyethylene glycol (PEG) polymeric coatings that mimic the surface charge distribution of proteins typically found in blood, which are known to show low aggregation under normal blood conditions. Here, we show that NPs with coatings based on apoferritin or human serum albumin display better antifouling properties and weaker protein interaction compared to similar NPs carrying conventional PEG polymeric coatings.

Background The temporalis muscle flap transfer with fascia lata augmentation (FLA) is a promising method for smile reconstruction after facial palsy. International literature lacks a detailed anatomical analysis of the temporalis muscle (TPM) combined with fascia lata (FL) augmentation. This study aims to describe the muscle's properties and calculate the length of FL needed to perform the temporalis muscle flap transfer with FLA. Methods Twenty nonembalmed male (m) and female (f) hemifacial cadavers were dissected to investigate the temporalis muscle's anatomy. Results The calculated minimum length of FL needed is 7.03cm (f) and 5.99cm (m). The length of the harvested tendon is 3.16cm/± 1.32cm (f) and 3.18/± 0.73cm (m). The length of the anterior part of the temporalis muscle (aTPM) is 4.16/± 0.80cm (f) and 5.30/± 0.85cm (m). The length of the posterior part (pTPM) is 5.24/± 1.51cm (f) and 6.62/± 1.03cm (m). The length from the most anterior to the most posterior point (aTPMpTPM) is 8.60/± 0.98cm (f) and 10.18/± 0.79cm (m). The length from the most cranial point to the distal tendon (cTPMdT) is 7.90/± 0.43cm (f) and 9.79/± 1.11cm (m). Conclusions This study gives basic information about the temporalis muscle and its anatomy to support existing and future surgical procedures in their performance. The recommended minimum length of FL to perform a temporalis muscle transfer with FLA is 7.03cm for female and 5.99cm for male, and minimum width of 3 cm. We recommend harvesting some extra centimeters to allow adjusting afterward.

With the aid of nanoscopic Raman spectroscopy, we track the interaction between the injected hot electrons and phonons in Bi2Se3 nanoribbon.

International audience; Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

Aging can cause morphological transformation in human microglia indicative of cell senescence, termed microglial dystrophy. However, cellular senescence is characterized by additional changes, such as an irregular cell cycle arrest, and a variety of metabolic and molecular changes including a senescence-associated secretory phenotype, dysfunction of degradation mechanisms, and altered DNA damage response. Here, we tested whether dystrophic microglia display customary markers of cell senescence by performing double and triple staining in sections of the temporal lobe and brain stem from 14 humans. We found that markers related to oxidative damage, such as upregulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), hemeoxygenase-1 (HO-1), and y-H2AX, as well as inclusion of lipofuscin, do not or only exceptionally colocalize with dystrophic microglia. Further, we did not observe a decline in lamin B1 around nuclear laminae in either dystrophic or ramified microglia within the same microscopic field. Only ferritin expression, which is known to increase with aging in CNS microglia, was frequently observed in dystrophic, but rarely in ramified microglial cells. We conclude that neither dystrophic nor ramified microglia in human brain exhibit significant expression of conventional senescence markers associated with oxidative stress, and that ferritin is the dominant immunophenotypic change related to microglial aging. We suggest that multiple pathogenic mechanisms other than those driving cellular senescence contribute to dystrophic transformation of microglia.

Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 36 Nr. 8 (1983): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents.

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents.

ZusammenfassungDas SMILE-Verfahren scheint mit einer geschätzten Inzidenz von 0,011% unter allen gängigen keratorefraktiven Verfahren das geringste Risiko für eine postoperative Keratektasie aufzuweisen. Dennoch kann zum jetzigen Zeitpunkt aufgrund der Neuheit des Verfahrens sowie der mangelnden Datenlage diesbezüglich keine eindeutige Überlegenheit gegenüber der Femto-LASIK oder PRK ausgesprochen werden. Insofern sind die identischen, strengen Kriterien zur Indikationsstellung analog zu den Excimer-basierten Verfahren von großer Bedeutung, um das Risiko einer Hornhautektasie zu minimieren. Additiv zur konventionellen Hornhauttomografie sollten neuere bildgebende Modalitäten wie OCT-basiertes Epithel-Mapping standardmäßig zum präoperativen Screening vor keratorefraktiven Eingriffen eingesetzt werden. Mit dem kornealen Crosslinking steht eine etablierte Behandlungsmethode der Post-SMILE-Keratektasie zur Verfügung, die insbesondere in frühen Stadien hohe Erfolgschancen verspricht. Der vorgelegte Fallbericht legt diese Sachverhalte genauer dar.

Purpose The study of shame has a long tradition in intra- and inter-personal psychology. This paper aims to investigate whether consumers can experience brand shame after self-relevant consumption incidents. Specifically, this research proposes that consumers follow a complex shame-inducing process in the aftermath of unpleasant experiences involving their favorite brand. The moderating role of relational tie strength between consumers and their favorite brand existing prior to symbolic failures is examined. Design/methodology/approach A scenario-based, online survey (n = 660) among consumers who have recently experienced a self-relevant failure with their favorite brand was conducted. Confirmatory factor analysis ensured the reliability and validity of the measurement model. For testing the conceptual model, data was analyzed by means of a moderated mediation analysis. The proposed model was tested against, among others, common method bias and alternative models. The findings were cross-validated with a scenario-based online experiment (n = 1,616). Findings Results show that brand shame is a key mediator between customer dissatisfaction and brand anger when self-relevant, symbolic failures happen. Moreover, strong consumer-brand identification triggers brand-detrimental effects. It is shown to influence the connection between consumers’ inward- (i.e. brand shame) and resulting outward-directed (i.e. brand anger) negative emotions on brands, which lead to consumer vengeance. Originality/value To the best of the authors’ knowledge, this research is the first to introduce the concept of situational brand shame to the literature on favorite brands. Furthermore, it shows that consumer-brand identification moderates the direct and indirect (via brand shame) unfavorable effects of failure-induced dissatisfaction on brand anger. This research adds insights to the investigation of the “love-becomes-hate” effect arising after self-relevant failures involving consumers’ most preferred brand.

Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 30 Nr. 3 (1977): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

A typical approach to tackle stochastic control problems with partial observation is to separate the control and estimation tasks. However, it is well known that this separation generally fails to deliver an actual optimal solution for risk-sensitive control problems. This paper investigates the separability of a general class of risk-sensitive investment management problems when a finite-dimensional filter exists. We show that the corresponding separated problem, where instead of the unobserved quantities, one considers their conditional filter distribution given the observations, is strictly equivalent to the original control problem. We widen the applicability of the so-called Modified Zakai Equation (MZE) for the study of the separated problem and prove that the MZE simplifies to a PDE in our approach. Furthermore, we derive criteria for separability. We do not solve the separated control problem but note that the existence of a finite-dimensional filter leads to a finite state space for the separated problem. Hence, the difficulty is equivalent to solving a complete observation risk-sensitive problem. Our results have implications for existing risk-sensitive investment management models with partial observations in that they establish their separability. Their implications for future research on new applications is mainly to provide conditions to ensure separability.

In this paper, we consider a generic interest rate market in the presence of roll-over risk, which generates spreads in spot/forward term rates. We do not require classical absence of arbitrage and rely instead on a minimal market viability assumption, which enables us to work in the context of the benchmark approach. In a Markovian setting, we extend the control theoretic approach of Gombani & Runggaldier (2013) and derive representations of spot/forward spreads as value functions of suitable stochastic optimal control problems, formulated under the real-world probability and with power-type objective functionals. We determine endogenously the funding-liquidity spread by relating it to the risk-sensitive optimization problem of a representative investor., 22 pages

The growing use of multimodal high-resolution volumetric data in pre-clinical studies leads to challenges related to the management and handling of the large amount of these datasets. Contrarily to the clinical context, currently there are no standard guidelines to regulate the use of image compression in pre-clinical contexts as a potential alleviation of this problem. In this work, the authors study the application of lossy image coding to compress high-resolution volumetric biomedical data. The impact of compression on the metrics and interpretation of volumetric data was quantified for a correlated multimodal imaging study to characterize murine tumor vasculature, using volumetric high-resolution episcopic microscopy (HREM), micro-computed tomography (µCT), and micro-magnetic resonance imaging (µMRI). The effects of compression were assessed by measuring task-specific performances of several biomedical experts who interpreted and labeled multiple data volumes compressed at different degrees. We defined trade-offs between data volume reduction and preservation of visual information, which ensured the preservation of relevant vasculature morphology at maximum compression efficiency across scales. Using the Jaccard Index (JI) and the average Hausdorff Distance (HD) after vasculature segmentation, we could demonstrate that, in this study, compression that yields to a 256-fold reduction of the data size allowed to keep the error induced by compression below the inter-observer variability, with minimal impact on the assessment of the tumor vasculature across scales.

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Figure S1. Flow chart of the data selection process for a pooled analysis of the prognostic relevance of circulating tumor cells in early breast cancer. Patients were ineligible if no valid data on CTC presence at the time of primary diagnosis as assessed using the FDA-cleared CellSearch® System were available (e.g., because of insufficient amount of blood or test failure). * A total of 3,754 patients with early breast cancer were randomized in the SUCCESS A clinical trial; however, blood samples for the enumeration of CTCs with the CellSearch® System were only collected after written informed consent from 1,994 of those patients.

Purpose: p95HER2 is an NH2-terminally truncated form of HER2 that lacks the trastuzumab binding site and is therefore thought to confer resistance to trastuzumab treatment. In this report, we introduce a new antibody that has enabled the first direct quantitative measurement of p95HER2 in formalin-fixed paraffin-embedded (FFPE) breast cancer tissues. We sought to show that quantitative p95HER2 levels would correlate with outcome in trastuzumab-treated HER2-positive metastatic breast cancer.Experimental Design: The novel p95HER2 antibody used here was characterized for sensitivity, specificity, and selectivity over full-length HER2. Quantitative p95HER2 levels were measured in 93 metastatic breast tumors using a VeraTag FFPE assay to determine the correlation of p95HER2 levels with outcomes.Results: Within a cohort of trastuzumab-treated metastatic breast cancer patients, high levels of p95HER2 were found to correlate with shorter progression-free survival [hazard ratio (HR), 1.9; P = 0.017] and overall survival (HR, 2.2; P = 0.012) in patients with tumors selected to be HER2 positive by the VeraTag HER2 assay. For those with tumors found to be fluorescence in situ hybridization positive, elevated p95HER2 correlated similarly with shorter progression-free survival (HR, 1.8; P = 0.022) and overall survival (HR, 2.2; P = 0.009).Conclusions: We have successfully generated an antibody that can specifically detect p95HER2, and developed an assay to quantify expression in FFPE tumor specimens. Using this novel assay, we have identified a group of HER2-positive patients expressing p95HER2 that have a worse outcome while on trastuzumab. As p95HER2 retains sensitivity to kinase inhibitors, measurement of p95HER2 in breast tumor sections may be useful in guiding treatment for patients with HER2-positive breast cancer. Clin Cancer Res; 16(16); 4226–35. ©2010 AACR.

Figure S3. Kaplan-Meier plots of overall survival according to the presence of circulating tumor cells at the time of primary breast cancer diagnosis. Panel A shows the predefined low-risk (T1/N0) patient subgroup, and Panel B shows the high-risk (T234/N123) patient subgroup.

Purpose: Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTC) in the peripheral blood of patients with metastatic breast cancer, less evidence is available for the prognostic relevance of CTCs at the time of primary diagnosis.Experimental Design: We conducted a pooled analysis of individual data from 3,173 patients with nonmetastatic (stage I–III) breast cancer from five breast cancer institutions. The prevalence and numbers of CTCs were assessed at the time of primary diagnosis with the FDA-cleared CellSearch System (Janssen Diagnostics, LLC). Patient outcomes were analyzed using meta-analytic procedures, univariate log-rank tests, and multivariate Cox proportional hazard regression analyses. The median follow-up duration was 62.8 months.Results: One or more CTCs were detected in 20.2% of the patients. CTC-positive patients had larger tumors, increased lymph node involvement, and a higher histologic tumor grade than did CTC-negative patients (all P < 0.002). Multivariate Cox regressions, which included tumor size, nodal status, histologic tumor grade, and hormone receptor and HER2 status, confirmed that the presence of CTCs was an independent prognostic factor for disease-free survival [HR, 1.82; 95% confidence interval (CI), 1.47–2.26], distant disease-free survival (HR, 1.89; 95% CI, 1.49–2.40), breast cancer–specific survival (HR, 2.04; 95% CI, 1.52–2.75), and overall survival (HR, 1.97; 95% CI, 1.51–2.59).Conclusions: In patients with primary breast cancer, the presence of CTCs was an independent predictor of poor disease-free, overall, breast cancer–specific, and distant disease-free survival. Clin Cancer Res; 22(10); 2583–93. ©2016 AACR.

Figure S2. Hazard ratios (black line) and 95% confidence intervals (blue area) from the univariate survival analyses according to the presence of CTCs categorized using different cutoff values (e.g., cutoff 0: 0 CTCs vs. > 0; cutoff 1: 0-1 CTCs vs. > 1; cutoff 2: 0-2 CTCs vs. > 2). Panel A shows breast-cancer-specific survival, and Panel B shows distant disease-free survival.

CCR Translation for This Article from Quantitation of p95HER2 in Paraffin Sections by Using a p95-Specific Antibody and Correlation with Outcome in a Cohort of Trastuzumab-Treated Breast Cancer Patients

Table S1. Patients and study variables according to study center for the pooled analysis of circulating tumor cells in early breast cancer

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Supplementary Figure 3 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Supplementary Figure 5 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a novel treatment modality in oncology. Preclinical findings suggest that long-term clinical outcomes may improve with blockade of additional proangiogenic receptor tyrosine kinases: platelet-derived growth factor receptors (PDGFR) and fibroblast growth factor receptors (FGFR). BIBF 1120 is an indolinone derivative potently blocking VEGF receptor (VEGFR), PDGFR and FGFR kinase activity in enzymatic assays (IC50, 20–100 nmol/L). BIBF 1120 inhibits mitogen-activated protein kinase and Akt signaling pathways in three cell types contributing to angiogenesis, endothelial cells, pericytes, and smooth muscle cells, resulting in inhibition of cell proliferation (EC50, 10–80 nmol/L) and apoptosis. In all tumor models tested thus far, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model, BIBF 1120 is highly active at well-tolerated doses (25–100 mg/kg daily p.o.), as measured by magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and inducing profound growth inhibition. A distinct pharmacodynamic feature of BIBF 1120 in cell culture is sustained pathway inhibition (up to 32 hours after 1-hour treatment), suggesting slow receptor off-kinetics. Although BIBF 1120 is rapidly metabolized in vivo by methylester cleavage, resulting in a short mean residence time, once daily oral dosing is fully efficacious in xenograft models. These distinctive pharmacokinetic and pharmacodynamic properties may help explain clinical observations with BIBF 1120, currently entering phase III clinical development. [Cancer Res 2008;68(12):4774–82]

Supplementary Figure 2 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Supplementary Figure Legends 1-5 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Supplementary Table 2 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Supplementary Methods, Figure 1, Table 1 from BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy

Supplementary Figure 1 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Supplementary Figure 4 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Supplementary Table 1 from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers

Supplementary Methods from Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers