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    The Temporal Doppler Effect: When The Future Feels Closer Than The Past

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    People routinely remember events that have passed and imagine those that are yet to come. The past and the future are sometimes psychologically close ( just around the corner ) and other times psychologically distant ( ages away ). Four studies demonstrate a systematic asymmetry whereby future events are psychologically closer than past events of equivalent objective distance. When considering specific times (e.g., 1 year) or events (e.g., Valentine\u27s Day), people consistently reported that the future was closer than the past. We suggest that this asymmetry arises because the subjective experience of movement through time (whereby future events approach and past events recede) is analogous to the physical experience of movement through space. Consistent with this hypothesis, experimentally reversing the metaphorical arrow of time (by having participants move backward through virtual space) completely eliminated the past-future asymmetry. We discuss how reducing psychological distance to the future may function to prepare people for upcoming action

    Comparison of monoclonal antibodies 17-1A and 323/A3: the influence of the affinity on tumour uptake and efficacy of radioimmunotherapy in human ovarian cancer xenografts.

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    The low-affinity monoclonal antibody (MAb) chimeric 17-1A(c-17-1A) and the high-affinity MAb mouse 323/A3 (m-323/A3) were used to study the effect of the MAb affinity on the tumour uptake and efficacy of radioimmunotherapy in nude mice bearing subcutaneously the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. Both MAbs are directed against the same pancarcinoma glycoprotein. In vitro, the number of binding sites on tumour cells at 4 degrees C was similar for both MAbs, but m-323/A3 had an approximately 5-fold higher affinity (1.3-3.0x10(9) M-1) than c-17-1A (3.0-5.4x10(8) M-1). This difference in affinity was more extreme at 37 degrees C, when no binding of c-17-1A could be observed. MAb m-323/A3 completely blocked binding of c-17-1A to tumour cells, whereas the reverse was not observed. Immunohistochemistry showed a similar but more intense staining pattern of m-323/A3 in human ovarian cancer xenografts than of c-17-1A. In vivo, the blood clearance in non-tumour-bearing nude mice was similar for both MAbs with terminal half-lives of 71.4 h for m-323/A3 and 62.7 h for c-17-1A. MAb m-323/A3 targeted better to tumour tissue, but was more heterogeneously distributed than c-17-1A. The cumulative absorbed radiation dose delivered by m-323/A3 to tumour tissue was 2.5- to 4.7-fold higher than that delivered by c-17-1A. When mice were treated with equivalent radiation doses of 131(I)m-323/A3 and 131(I)c-17-1A, based on a correction for the immunoreactivity of the radiolabelled MAbs, m-323/A3 induced a better growth inhibition in two of the three xenografts. When the radiation doses were adjusted to obtain a similar amount of radiation in the tumour c-17-1A was more effective in tumour growth inhibition in all three xenografts

    Empathy Gaps Between Helpers and Help-Seekers: Implications for Cooperation

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    Help-seekers and potential helpers often experience an “empathy gap” – an inability to understand each other’s unique perspectives. Both parties are concerned about their reputation, self-esteem, and relationships, but these concerns differ in ways that lead to misinterpretation of the other party’s actions, and, in turn, missed opportunities for cooperation. In this article, we review research that describes the role-specific concerns of helpers and help-seekers. We then review studies of emotional perspective-taking, which can help explain why help-seekers and helpers often experience empathy gaps. We go on to discuss recent work that illustrates the consequences of empathy gaps between helpers and help-seekers—social prediction errors that prevent helping and misguided intentions that can lead to unhelpful help. Finally, we discuss some promising directions for future research

    Patients' appreciation of pre-implant augmentation of the severely resorbed maxilla with calvarial or anterior iliac crest bone:a randomized controlled trial

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    BACKGROUND: Little is known about the impact of bone graft harvesting for pre-implant augmentation of the maxilla from a patient's perspective. To assess patient-reported outcome measures (PROMs) related to augmentation of the extremely resorbed edentulous maxilla with calvarial or anterior iliac crest bone. MATERIALS AND METHODS: For this randomised controlled trial, 20 consecutive edentulous patients needing extensive pre-implant surgery of the maxilla were randomly assigned to either calvarial (n = 10) or anterior iliac crest (n = 10) bone harvesting. Patient reports on procedure-related satisfaction, questionnaires on oral functionality (denture satisfaction, chewing ability) and oral health-related quality of life (OHIP-49NL) and subjective donor site-related outcomes (e.g. of post-operative pain, scar formation, physical mobility) were assessed. RESULTS: Irrespective of the harvesting site, patients were generally satisfied (median VAS score 93 (86-99) mm, p = 0.400) with the procedure and its final results. Post-operative pain was mild (median 40 (20-40) mm) and decreased to no pain (4 (0-16) mm) within 14 days. Early post-operative pain was significantly higher following anterior iliac crest harvesting (p < 0.00). Impact on physical mobility, daily functioning and satisfaction with the scar formation were similar in both groups. CONCLUSIONS: The assessed PROMs confirmed that bone graft harvesting from the calvarium or anterior iliac crest is an appropriate procedure, reflected by high levels of satisfaction, minor long-term sequela and improvement of perceived oral health. For clinical decision-making, decisions can be based on individual features and preferences. TRIAL REGISTRATION: NTR, NTR3968 , registered 1 July 2013

    Drug resistance features and S-phase fraction as possible determinants for drug response in a panel of human ovarian cancer xenografts

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    Multidrug resistance (MDR) and more specifically the expression of P-glycoprotein (Pgp) have been studied extensively in vitro. Unfortunately, it appears that the predictive value of MDR recognized in vitro is mostly an incorrect measure to determine the responsiveness of a particular tumour in the clinic. This misunderstood or overvalued role of MDR might explain the failure of strategies to reverse Pgp function by the use of modulators in solid tumours. To obtain more insight in in vivo drug resistance we investigated a panel of 15 human ovarian cancer xenografts consisting of the most common histological subtypes known in ovarian cancer patients. The response rate to cisplatin, cyclophosphamide and doxorubicin in the xenografts resembled the results of phase II trials with these agents in ovarian cancer patients. This resemblance justifies drug resistance studies in this experimental in vivo human tumour system. We determined the expression levels of MDR 1, MRP 1, LRP and topoisomerase IIα mRNA by the RNase protection assay and the presence of MRP1 and LRP proteins by immunohistochemistry. The S-phase fraction was investigated as a separate parameter by flow cytometry. In none of the 15 ovarian cancer xenografts was MDR 1 expression detectable. The expression levels of MRP 1 and LRP were low to moderate and resembled the presence of the MRP1 and LRP proteins. There was a weak, inverse relationship between the expression levels of LRP and sensitivity to cisplatin and cyclophosphamide (r = –0.44 and –0.45), but not to doxorubicin. The levels of topoisomerase IIα varied among the xenografts (0.73–2.66) and failed to correlate with doxorubicin resistance (r = 0.14). The S-phase fraction, however, showed a relation with the sensitivity to cisplatin (r = 0.66). Among the determinants studied in ovarian cancer in vivo, LRP mRNA and the S-phase fraction were the best predictive factors for drug response and most specifically for the activity of cisplatin. © 2000 Cancer Research Campaig
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