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In industrial product development with customers, it is well‐known that lead userness is associated with novel and commercially attractive products. We take a next step by analyzing if lead userness is related to product development that potentially affects industry‐level practices. Our main hypothesis is that lead userness results in the pursuit of Schumpeterian product opportunities: disequilibrating, radical, rare, and based on new knowledge and creative activities. In contrast, at low lead userness, more Kirznerian product opportunities are expected—which maintain industry standards. The hypothesis is supported by data from 139 high‐tech small firms. Next, we anticipate that factors related to the selection of lead users, and the effective processing of their inputs, moderate the connection between lead userness and Schumpeterian opportunity. As for selection, we find a stronger connection when firms collaborate with "new" customers. Conversely, when involved customers have been business partners already for a long time, the pursuit of Schumpeterian opportunities is mitigated. Also, tentative evidence is found that the connection between lead userness and Schumpeterian opportunity amplifies when involved customers are less dominant market players. Finally, when it comes to processing lead users' input, we report tentative evidence that firms' R&D intensity should be higher (indicating ability to process lead users' inputs and make continued development efforts). Our findings help to explain why lead users have been associated with industry dynamics, and provide guidance to identify "relevant" lead users when firms seek product opportunities that potentially disequilibrate their industry. [ABSTRACT FROM AUTHOR]

Innovation‐related knowledge can be voluntarily transferred to other organizations for direct or indirect benefits, but firms can also suffer from involuntary transfer when their knowledge leaks and gets stolen. Despite its relevance to managers, outbound knowledge transfer has been understudied. Previous theoretical perspectives suggest that the primary reason why firms innovate—to conquer markets with product innovation or to improve internal processes with process innovation—matters for how outbound knowledge transfer takes shape. Also, higher stakes represented by innovation development cost can be expected to moderate the relationship between innovation type and outbound transfer. We analyse survey data of 176 high‐tech small firms to find that, indeed, process innovations are much more likely shared voluntarily, although product innovations leak away without the firm's consent. Development cost moderates voluntary transfer: Low‐cost process innovations are barely shared, reflecting a lack of adopter interest, whereas high‐cost process innovations are more likely to leak away to similar levels as product innovations. Overall, high‐tech small firms are more inclined to voluntary transfer their process innovations. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported tumor volume underestimation with multiparametric (mp)MRI in prostate cancer diagnosis.Purpose: To investigate why some parts of lesions are not visible on mpMRI by comparing their histopathology features to those of visible regions.Study Type: Retrospective.Population: Thirty-four patients with biopsy-proven prostate cancer scheduled for prostatectomy (median 68.7 years).Field Strength/sequence: T2 -weighted, diffusion-weighted imaging, T2 mapping, and dynamic contrast-enhanced MRI on two 3T systems and one 1.5T system.Assessment: Two readers delineated suspicious lesions on mpMRI. A pathologist delineated the lesions on histopathology. A patient-customized mold enabled the registration of histopathology and MRI. On histopathology we identified mpMRI visible and invisible lesions. Subsequently, within the visible lesions we identified regions that were visible and regions that were invisible on mpMRI. For each lesion and region the following characteristics were determined: size, location, International Society of Urological Pathology (ISUP) grade, and Gleason subpatterns (density [dense/intermediate], tumor morphology [homogeneous/heterogeneous], cribriform growth [yes/no]).Statistical Tests: With generalized linear mixed-effect modeling we investigated which features explain why a lesion or a region was invisible on MRI. We compared imaging values (T2 , ADC, and Ktrans ) for these features with one-way analysis of variance (ANOVA).Results: Small, anterior, and ISUP grade 1-2 lesions (n = 34) were missed more frequent than large, posterior, ISUP grade ≥ 3 lesions (n = 35). Invisible regions on mpMRI had lower tumor density, heterogeneous tumor morphology, and were located in the transition zone. Both T2 and ADC values were higher in "intermediate" compared with "dense" regions (P = 0.002 and < 0.001) and in regions with heterogeneous compared with homogeneous morphology (P < 0.001 and 0.03). Ktrans was not significantly different (P = 0.24 and 0.99).Data Conclusion: Regions of prostate cancer lesions that are invisible on mpMRI have different histopathology features than visible regions. This may have implications for monitoring during active surveillance and focal treatment strategies.Level Of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1235-1246. [ABSTRACT FROM AUTHOR]

Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next‐generation sequencing, conducted in situ and immunohistochemical analyses (including PD‐L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan‐Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5‐year overall survival (OS) of 58% and recurrence‐free survival (RFS) of 45% was detected. Sequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%). Gene amplifications were found in EGFR (5%), ERBB2 (2%), and MET (2%). We detected no evidence of MMR‐deficiency (MMR‐d)/MSI‐high (MSI‐h), whereas 10 of 63 cases (16%) expressed PD‐L1. Therefore, anti‐PD‐1/PD‐L1 immunotherapy approaches might be tested in UrC. Importantly, we found aberrations in intracellular signal transduction pathways (RAS/RAF/PI3K) in 31% of UrCs with potential implications for anti‐EGFR therapy. Less frequent potentially actionable genetic alterations were additionally detected in ERBB2 (HER2), MET, FGFR1, and PDGFRA. The molecular profile strengthens the notion that UrC is a distinct entity on the genomic level with closer resemblance to colorectal than to bladder cancer. [ABSTRACT FROM AUTHOR]

Fibroblasts are abundantly present in the prostate tumor microenvironment (TME), including cancer‐associated fibroblasts (CAFs) which play a key role in cancer development. Androgen receptor (AR) signaling is the main driver of prostate cancer (PCa) progression, and stromal cells in the TME also express AR. High‐grade tumor and poor clinical outcome are associated with low AR expression in the TME, which suggests a protective role of AR signaling in the stroma against PCa development. However, the mechanism of this relation is not clear. In this study, we isolated AR‐expressing CAF‐like cells. Testosterone (R1881) exposure did not affect CAF‐like cell morphology, proliferation, or motility. PCa cell growth was not affected by culturing in medium from R1881‐exposed CAF‐like cells; however, migration of PCa cells was inhibited. AR chromatin immune precipitation sequencing (ChIP‐seq) was performed and motif search suggested that AR in CAF‐like cells bound the chromatin through AP‐1‐elements upon R1881 exposure, inducing enhancer‐mediated AR chromatin interactions. The vast majority of chromatin binding sites in CAF‐like cells were unique and not shared with AR sites observed in PCa cell lines or tumors. AR signaling in CAF‐like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling. [ABSTRACT FROM AUTHOR]

Drawing on theories of perspective-taking and i-deals, this study explores the impact of supervisors' own caregiving responsibilities for elders and parental status on subordinates' schedule i-deals. Moreover, we investigate the extent to which schedule i-deals mediate the relationship between supervisors' caregiving responsibilities and two employee outcomes: satisfaction with work-family balance and turnover intentions. Using a sample of 520 dyads involving 137 supervisors and 520 employees, the results of multilevel analysis show that supervisors' caregiving responsibilities for elders is positively related to schedule i-deals, but their parental status is not. The findings also show that schedule i-deals mediate the effect of supervisors' caregiving responsibilities for elders on subordinates' satisfaction with work-family balance and turnover intentions. This research contributes to the i-deals' literature by focusing on the role of managers' own caregiving responsibilities in facilitating the provision of schedule i-deals to their subordinates and by exploring the consequences of schedule i-deals to gain an understanding of the mutually beneficial nature of such deals. From a practical point of view, supervisors and HR departments might utilise schedule i-deals to drive desirable employee outcomes, in particular their caregiving responsibilities, and to engender a family-supportive organisational culture. [ABSTRACT FROM AUTHOR]

Oncogenic fusion genes that involve kinases have proven to be effective targets for therapy in a wide range of cancers. Unfortunately, the diagnostic approaches required to identify these events are struggling to keep pace with the diverse array of genetic alterations that occur in cancer. Diagnostic screening in solid tumours is particularly challenging, as many fusion genes occur with a low frequency. To overcome these limitations, we developed a capture enrichment strategy to enable high-throughput transcript sequencing of the human kinome. This approach provides a global overview of kinase fusion events, irrespective of the identity of the fusion partner. To demonstrate the utility of this system, we profiled 100 non-small cell lung cancers and identified numerous genetic alterations impacting fibroblast growth factor receptor 3 ( FGFR3) in lung squamous cell carcinoma and a novel ALK fusion partner in lung adenocarcinoma. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Both scientists and practitioners emphasize the importance of innovative work behaviour (IWB) of individual employees for organizational success, but the measurement of IWB is still at an evolutionary stage. This article is concerned with developed a measure of IWB with four potential dimensions: the exploration, generation, championing and implementation of ideas. From a pilot survey among 81 research professionals and their supervisors, we derived an initial version of ten items. Next, analysis of validity drew on survey data from 703 matched dyads of knowledge workers and their supervisors in 94 knowledge intensive services firms. It included confirmatory factor analyses and hierarchical multilevel regressions to test hypothesized relationships of IWB with related constructs, including participative leadership, external work contacts and innovative output. These analyses demonstrated sufficient reliability and criterion validity. Evidence for the distinctiveness of the four dimensions was, however, weak, suggesting that IWB is one-dimensional. We conclude that further research on this issue is merited. [ABSTRACT FROM AUTHOR]

The present study evaluates several critical issues related to precision and accuracy of Cu and Zn isotopic measurements with application to estuarine particulate materials. Calibration of reference materials (such as the IRMM 3702 Zn) against the JMC Zn and NIST Cu reference materials were performed in wet and/or dry plasma modes (Aridus I and DSN-100) on a Nu Plasma MC-ICP-MS. Different mass bias correction methods were compared. More than 100 analyses of certified reference materials suggested that the sample-calibrator bracketing correction and the empirical external normalisation methods provide the most reliable corrections, with long term external precisions of 0.06 and 0.07‰ (2SD), respectively. Investigation of the effect of variable analyte to spike concentration ratios on Zn and Cu isotopic determinations indicated that the accuracy of Cu measurements in dry plasma is very sensitive to the relative Cu and Zn concentrations, with deviations of δ65Cu from −0.4‰ (Cu/Zn = 4) to +0.4‰ (Cu/Zn = 0.2). A quantitative assessment (with instrumental mass bias corrections) of spectral and non-spectral interferences (Ti, Cr, Co, Fe, Ca, Mg, Na) was performed. Titanium and Cr were the most severe interfering constituents, contributing to inaccuracies of −5.1‰ and +0.60‰ on δ68/64Zn, respectively (for 500 μg l−1 Cu and Zn standard solutions spiked with 1000 μg l−1 of Ti or Cr). Preliminary isotopic results were obtained on contrasting sediment matrices from the Scheldt estuary. Significant isotopic fractionation of zinc (from 0.21‰ to 1.13‰ for δ66Zn) and copper (from −0.38‰ to 0.23‰ for δ65Cu), suggest a control by physical mixing of continental and marine water masses, characterized by distinct Cu and Zn isotopic signatures. These results provide a stepping-stone to further evaluate the use of Cu and Zn isotopes as biogeochemical tracers in estuarine environments. [ABSTRACT FROM AUTHOR]

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The increased use of temporary contracts has instigated debates on possible implications for employees’ attitudes, well-being and behaviour. The complex issues related to this debate are reviewed from a theoretical, empirical and conceptual point of view. First, the definitions of temporary employment that are currently used in OECD countries are reviewed. Second, theoretical views concerning possible determinants are elaborated. The theoretical frameworks discussed include Work Stress Theory, Social Comparison Theory and Social Exchange Theory. The determinants proposed in these theories have served to form the basis of hypotheses on differences between temporary and permanent workers on various psychological outcomes. Third, research on associations between temporary employment and the variables job satisfaction, organizational commitment, well-being and behaviour are reviewed. These variables are most frequently used in the realm of temporary work research. This review concludes that research results have been inconsistent and inconclusive, unlike the predictions that follow from the theoretical frameworks. This leads to a fourth section in which potential explanations for these inconsistent findings are advanced. In conclusion, a conceptual model is developed to inspire future research. [ABSTRACT FROM AUTHOR]

The JKT-1 cell line has been used in multiple independent studies as a representative model of human testicular seminoma. However, no cell line for this specific tumour type has been independently confirmed previously; and therefore, the seminomatous origin of JKT-1 must be proven. The genetic constitution of the JKT-1 cells was determined using flow cytometry and spectral karyotyping, as well as array comparative genomic hybridization and fluorescent in situ hybridization. Marker profiling, predominantly based on differentially expressed proteins during normal germ cell development, was performed by immunohistochemistry and Western blot analyses. Moreover, genome wide affymetrix mRNA expression and profiling of 157 microRNAs was performed, and the status of genomic imprinting was determined. A germ cell origin of the JKT-1 cells was in line with genomic imprinting status and marker profile (including positive staining for several cancer-testis antigens). However, the supposed primary tumour, from which the cell line was derived, being indeed a classical seminoma, was molecularly proven not to be the origin of the cell line. The characteristic chromosomal anomalies of seminoma, e.g. gain of the short arm of chromosome 12, as well as the informative marker profile (positive staining for OCT3/4, NANOG, among others) were absent in the various JKT-1 cell lines investigated, irrespective of where the cells were cultured. All results indicate that the JKT-1 cell line is not representative of human seminoma. Although it can originate from an early germ cell, a non-germ cell derivation cannot be excluded. [ABSTRACT FROM AUTHOR]

Aims To investigate the relationship between the use of antidepressants with or without NSAIDs and the risk of gastrointestinal side-effects. Methods This was a population-based cohort study. Medication data of 180 000 patients from 16 pharmacies in The Netherlands were studied. The subjects were a group of 15 445 new users of antidepressants with or without NSAIDs. A review of patient profiles for cases of gastrointestinal adverse effects caused by first time use of antidepressants with or without NSAIDs was carried out. The number of first prescriptions for peptic ulcer drugs (Anatomical Therapeutic Chemical classification A02B) in the period from day 2 after starting antidepressants with or without NSAIDs until 10 days after the last dose was the main outcome measure. Results In the reference group of 619 new users of nonselective antidepressants (TCAs), the incidence of first prescriptions for peptic ulcer drugs was 0.051 (95% confidence interval 0.021, 0.105). The use of SSRIs (n = 1181) caused a slightly higher incidence rate ratio (IRR) of 1.2 (0.5, 2.8). The combined use of SSRIs and NSAIDs (n = 86) increased the IRR to 12.4 (3.2, 48.0). In contrast, the combination of nonselective antidepressants and NSAIDs (n = 74) increased the IRR to 2.5 (0.3, 20.3). Conclusions SSRIs increase the risk of gastrointestinal adverse effects in first time users as compared with nonselective antidepressants. The combined use of SSRIs and NSAIDs strongly increases the risk of gastrointestinal adverse effects and should be avoided. The combination of nonselective antidepressants and NSAIDs does not have this effect. [ABSTRACT FROM AUTHOR]

The article reports on the case of a 40-year-old woman with a progressive periventricular white matter lesion. The diagnosis showed diffusely infiltrating germinoma. The article describes the additional treatment and clinical progress of the patient. It explains that germinomas are tumors of germ cell origin and represent the brain counterpart of testicular seminoma.

Presents a letter to the editor responding to a comment the article "Combined use of NSAIDs and SSRIs increases the risk for gastrointestinal adverse effects."