502 research outputs found

    Valuing Loss Firms

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    We hypothesize that when confronted with a loss, investors price earnings conditional on the expected probability of the firm's return to profitability. We show a parsimonious model of one year-ahead loss reversal is useful in predicting the firm's return to profitability. Using the estimated probabilities of loss reversal to define samples of persistent (low probability of reversal) and transitory (high probability of reversal) losses, we show the pricing of losses, as well as their characteristics, varies as a function of their expected probability of reversal. We document a more pronounced stock price response to a transitory loss consistent with investors assessing the likelihood of exercising the abandonment option to be smaller. We also find the market responds negatively to persistent losses, especially in the latter part of the sample period. We also show the results are consistent with investors pricing the components of losses differently depending on the type of loss: they value only the aggregate accruals component of persistent losses and only the aggregate cash flow component of transitory losses. Further analysis shows the result for persistent losses relates to the presence of an increasingly larger R&D component that investors price negatively as if rewarding firms that make larger R&D outlays with larger returns. One consequence of the presence of a growing R&D component implies persistent losses become a weaker indicator of the likelihood of exercising the abandonment option

    Detection of amplified DNA sequences by reverse chromosome painting using genomic tumor DNA as probe

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    A modification of reverse chromosome painting was carried out using genomic DNA from tumor cells as a complex probe for chromosomal in situ suppression hybridization to normal metaphase chromsome spreads. Amplified DNA sequences contained in such probes showed specific signals, revealing the normal chromosome positions from which these sequences were derived. As a model system, genomic DNAs were analyzed from three tumor cell lines with amplification units including the proto-oncogene c-myc. The smallest amplification unit was about 90 kb and was present in 16–24 copies; the largest unit was bigger than 600 kb and was present in 16–32 copies. Specific signals that co-localized with a differently labeled c-myc probe on chromosome band 8q24 were obtained with genomic DNA from each cell line. In further experiments, genomic DNA derived from primary tumor material was used in the case of a male patient with glioblastoma multiforme (GBM). Southern blot analysis using an epidermal growth factor receptor gene (EGFR) probe that maps to 7p13 indicated the amplification of sequences from this gene. Using reverse chromosome painting, signals were found both on band 7p13 and bands 12q13–q15. Notably, the signal on 12q13–q15 was consistently stronger. The weaker 7p13 signal showed co-localization with the major signal of the differently labeled EGFR probe. A minor signal of this probe was seen on 12q13, suggesting cross-hybridization to ERB3 sequences homologous to EGFR. The results indicate co-amplification of sequences from bands 12q13–q15, in addition to sequences from band 7p13. Several oncogenes map to 12q13–q15 providing candidate genes for a tumor-associated proto-oncogene amplification. Although the nature of the amplified sequences needs to be clarified, this experiment demonstrates the potential of reverse chromosome painting with genomic tumor DNA for rapidly mapping the normal chromosomal localization of the DNA from which the amplified sequences were derived. In addition, a weaker staining of chromosomes 10 and X was consistently observed indicating that these chromosomes were present in only one copy in the GBM genome. This rapid approach can be used to analyze cases where no metaphase spreads from the tumor material are available. It does not require any preknowledge of amplified sequences and can be applied to screen large numbers of tumors

    The Performance of Publicly Traded European Venture Capital Companies

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    The stock market return and the risk of 33 quoted European venture capital companies during the period 1977-1991 are studied. The return is negative on average with eight of the 33 companies having a return that is higher than the market return. However, the systematic risk (measured by the beta of the stock) is lower than the market risk. When taking the risk into account, no company has a return that is significantly higher than zero, but four companies have a return that is significantly lower than zero. When interpreting these results, one has to take into account that most shares of venture capital companies trade at a significant discount relative to their net asset value, indicating that the long-term return that investors can expect in the future, may be higher than in the past. Venture capital companies that are specialized in a specific investment stage have a higher return, while the regional companies have a lower return than general companies. The systematic risk of specialized companies is higher than that of general companies

    Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization

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    Comparative genomic in situ hybridization (CGH) provides a new possibility for searching genomes for imbalanced genetic material. Labeled genomic test DNA, prepared from clinical or tumor specimens, is mixed with differently labeled control DNA prepared from cells with normal chromosome complements. The mixed probe is used for chromosomal in situ suppression (CISS) hybridization to normal metaphase spreads (CGH-metaphase spreads). Hybridized test and control DNA sequences are detected via different fluorochromes, e.g., fluorescein isothiocyanate (FITC) and tetraethylrhodamine isothiocyanate (TRITC). The ratios of FITC/TRITC fluorescence intensities for each chromosome or chromosome segment should then reflect its relative copy number in the test genome compared with the control genome, e.g., 0.5 for monosomies, 1 for disomies, 1.5 for trisomies, etc. Initially, model experiments were designed to test the accuracy of fluorescence ratio measurements on single chromosomes. DNAs from up to five human chromosome-specific plasmid libraries were labeled with biotin and digoxigenin in different hapten proportions. Probe mixtures were used for CISS hybridization to normal human metaphase spreads and detected with FITC and TRITC. An epifluorescence microscope equipped with a cooled charge coupled device (CCD) camera was used for image acquisition. Procedures for fluorescence ratio measurements were developed on the basis of commercial image analysis software. For hapten ratios 4/1, 1/1 and 1/4, fluorescence ratio values measured for individual chromosomes could be used as a single reliable parameter for chromosome identification. Our findings indicate (1) a tight correlation of fluorescence ratio values with hapten ratios, and (2) the potential of fluorescence ratio measurements for multiple color chromosome painting. Subsequently, genomic test DNAs, prepared from a patient with Down syndrome, from blood of a patient with Tcell prolymphocytic leukemia, and from cultured cells of a renal papillary carcinoma cell line, were applied in CGH experiments. As expected, significant differences in the fluorescence ratios could be measured for chromosome types present in different copy numbers in these test genomes, including a trisomy of chromosome 21, the smallest autosome of the human complement. In addition, chromosome material involved in partial gains and losses of the different tumors could be mapped to their normal chromosome counterparts in CGH-metaphase spreads. An alternative and simpler evaluation procedure based on visual inspection of CCD images of CGH-metaphase spreads also yielded consistent results from several independent observers. Pitfalls, methodological improvements, and potential applications of CGH analyses are discussed

    'A palliative end-stage COPD patient does not exist' : a qualitative study of barriers to and facilitators for early integration of palliative home care for end-stage COPD

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    Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD). However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD. General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD. Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed. Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients. Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers' education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC. The results provide insights for clinical practice and the development of key components for successful practice in a phase 0-2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients' disease insight and training PHC nurses in care for end-stage COPD

    Rejuvenating the ocean: mean ocean radiocarbon, CO2 release, and radiocarbon budget closure across the last deglaciation

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    Abstract. Radiocarbon is a tracer that provides unique insights into the ocean's ability to sequester CO2 from the atmosphere. While spatial patterns of radiocarbon in the ocean interior can indicate the vectors and timescales for carbon transport through the ocean, estimates of the global average ocean–atmosphere radiocarbon age offset (B-Atm) place constraints on the closure of the global carbon cycle. Here, we apply a Bayesian interpolation method to compiled B-Atm data to generate global interpolated fields and mean ocean B-Atm estimates for a suite of time slices across the last deglaciation. The compiled data and interpolations confirm a stepwise and spatially heterogeneous “rejuvenation” of the ocean, suggesting that carbon was released to the atmosphere through two swings of a “ventilation seesaw” operating between the North Atlantic and both the Southern Ocean and the North Pacific. Sensitivity tests using the Bern3D model of intermediate complexity demonstrate that a portion of the reconstructed deglacial B-Atm changes may reflect “phase-attenuation” biases that are unrelated to ocean ventilation and that arise from independent atmospheric radiocarbon dynamics instead. A deglacial minimum in B-Atm offsets during the Bølling–Allerød could partly reflect such a bias. However, the sensitivity tests further demonstrate that when correcting for such biases, ocean “ventilation” could still account for at least one-third of deglacial atmospheric CO2 rise. This contribution to CO2 rise appears to have continued through the Younger Dryas, though much of the impact was likely achieved by the end of the Bølling–Allerød, indicating a key role for marine carbon cycle adjustment early in the deglacial process. Our global average B-Atm estimates place further new constraints on the long-standing mystery of global radiocarbon budget closure across the last deglaciation and suggest that glacial radiocarbon production levels are likely underestimated on average by existing reconstructions. </jats:p

    Attenuated and Nonproductive Viral Transcription in the Lymphatic Tissue of HIV-1-Infected Patients Receiving Potent Antiretroviral Therapy

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    Human immunodeficiency virus type 1 (HIV-1) RNA that persists in the lymphoid tissue of patients despite treatment with highly active antiretroviral therapy (HAART) may represent extracellular virions or intracellular RNAs residing within HIV-infected cells. To further characterize residual viral transcription, tonsil biopsy specimens from patients receiving long-term HAART, untreated patients, and patients undergoing 2 weeks of structured treatment interruption were analyzed by polymerase chain reaction quantification of virion-encapsidated RNA, intracellular unspliced HIV RNA (HIV UsRNA), multiply spliced HIV RNA encoding tat and rev (HIV MsRNA), and HIV DNA. Tonsil biopsy specimens from viremic patients harbored high amounts of virions, which primarily stemmed from local production, as indicated by a strong correlation of extracellular tonsillar RNA with intracellular HIV-1 nucleic acid levels but not with plasma viremia, and as shown by phylogenetic analysis of clonal env sequences from lymphoid tissue and plasma. In patients receiving HAART, intracellular HIV UsRNA persisted at significantly decreased levels, whereas HIV MsRNA and lymphoid virion levels were depleted. Thus, residual lymphoid HIV-1 RNA in patients receiving HAART indicates attenuated viral transcription in HIV-1-infected cells that lack virion productio

    Development of a complex intervention for early integration of palliative home care into standard care for end-stage COPD patients : a phase 0-I study

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    Background : Research suggests that palliative home care should be integrated early into standard care for end-stage COPD patients. Patients also express the wish to be cared for and to die at home. However, a practice model for early integration of palliative home care (PHC) into standard care for end-stage COPD has not been fully developed. Aim : To develop an intervention for early integration of PHC into standard care for end-stage COPD patients. Methods : We conducted a Phase 0-I study according to the Medical Research Council Framework for the development of complex interventions. Phase 0 aimed to identify the inclusion criteria and key components of the intervention by way of an explorative literature search of interventions, expert consultations, and seven focus groups with general practitioners and community nurses on perceived barriers to and facilitators of early integrated PHC for COPD. In Phase 1, the intervention, its inclusion criteria and its components were developed and further refined by an expert panel and two expert opinions. Results : Phase 0 resulted in identification of inclusion criteria and components from existing interventions, and barriers to and facilitators of early integration of PHC for end-stage COPD. Based on these findings, a nurse-led intervention was developed in Phase I consisting of training for PHC nurses in symptom recognition and physical therapy exercises for end-stage COPD, regular visits by PHC nurses at the patients' homes, two information leaflets on selfmanagement, a semi-structured protocol and follow-up plan to record the outcomes of the home visits, and integration of care by enabling collaboration and communication between home and hospital-based professional caregivers. Conclusion : This Phase 0-I trial succeeded in developing a complex intervention for early integration of PHC for end-stage COPD. The use of three methods in Phase 0 gave reliable data on which to base inclusion criteria and components of the intervention. The preliminary effectiveness, feasibility and acceptability of the intervention will be subsequently tested in a Phase II study

    Delocalization of ultracold atoms in a disordered potential due to light scattering

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    We numerically study the expansion dynamics of ultracold atoms in a one-dimensional disordered potential in the presence of a weak position measurement of the atoms. We specifically consider this position measurement to be realized by a combination of an external laser and a periodic array of optical microcavities along a waveguide. The position information is acquired through the scattering of a near-resonant laser photon into a specific eigenmode of one of the cavities. The time evolution of the atomic density in the presence of this light scattering mechanism is described within a Lindblad master equation approach, which is numerically implemented using the Monte Carlo wave function technique. We find that an arbitrarily weak rate of photon emission leads to a breakdown of Anderson localization of the atoms.Comment: 7 pages, 8 figure
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