The end of the corporate life cycle

This paper asks how takeover and failure hazards change as listed firms get older. The hypothesis is that they increase because firms gradually run out of growth opportunities. We find the opposite. Both takeover and failure hazard drop significantly with age. The decline in takeover hazard can be explained with Loderer, Stulz, and Waelchli’s (2013) “buggy whip makers” hypothesis: Because old firms are comparatively well-managed and are affected by limited agency problems, on average, they offer little value added potential to acquirers. Failure hazard drops because to learning. The results are robust to various alternative interpretations and cannot be explained by unobserved heterogeneity. While hazards decline with age, they do not go to zero. This explains why, eventually, all listed firms disappear

Concentration-dependent isoflurane effects on withdrawal reflexes in pigs and the role of the stimulation paradigm

In this prospective two-phase experimental trial, 10 pigs were anaesthetized twice with isoflurane only. In the first phase, the individual minimum alveolar concentration (MAC) was determined and in the second phase the effects on withdrawal reflexes of increasing end-tidal isoflurane concentrations (from 1.6% to 2.8%) were assessed. Single, 10 and 60 repeated electrical stimulations were used to evoke withdrawal reflexes which were recorded and quantified by electromyography. Recruitment curves for reflex amplitude for increasing stimulation intensities and isoflurane concentrations were constructed. Isoflurane MAC was 1.9+/-0.3%. Reflexes evoked by repeated stimulation were suppressed at isoflurane concentrations significantly higher than those which suppressed complex movements during MAC determination (P=0.014 and P=0.006 for 10 and 60 repeated stimuli respectively). Isoflurane up to 2.8% was still not able to abolish reflex activity evoked by repeated stimulations in all pigs. Single stimulation reflexes were suppressed at significantly lower concentrations than repeated stimulation reflexes (P=0.008 and P=0.004 for 10 and 60 repeated stimuli, respectively). Reflex amplitude was significantly correlated with isoflurane concentration (P<0.001, r=-0.85) independent of the individual MAC. The findings indicate that the level at which isoflurane suppresses withdrawal reflexes is dependent on the stimulation paradigm (single vs. repeated electrical stimulation), and there is limited value in expressing reflex withdrawal suppression in terms of MAC as purposeful and reflex movements are independently affected by isoflurane in individual animals.

Identity, Philosophy, and the Problem of Armenian History in the Sixth Century

History and Identity in the Late Antique Near East gathers together the work of distinguished historians and early career scholars with a broad range of expertise to investigate the significance of newly emerged, or recently resurrected, ethnic identities on the borders of the eastern Mediterranean world. It focuses on the "long late antiquity" from the eve of the Arab conquest of the Roman East to the formation of the Abbasid caliphate. The first half of the book offers papers on the Christian Orient on the cusp of the Islamic invasions. These papers discuss how Christians negotiated the end of Roman power, whether in the selective use of the patristic past to create confessional divisions or the emphasis of the shared philosophical legacy of the Greco-Roman world. The second half of the book considers Muslim attempts to negotiate the pasts of the conquered lands of the Near East, where the Christian histories of Hira or Egypt were used to create distinctive regional identities for Arab settlers. Like the first half, this section investigates the redeployment of a shared history, this time the historical imagination of the Qu'ran and the era of the first caliphs. All the papers in the volume bring together studies of the invention of the past across traditional divides between disciplines, placing the re-assessment of the past as a central feature of the long late antiquity. As a whole, History and Identity in the Late Antique Near East represents a distinctive contribution to recent writing on late antiquity, due to its cultural breadth, its interdisciplinary focus, and its novel definition of late antiquity itself.

Identification of the signal pathways modulated by expression of p210$\rm\sp{bcr-abl}$ and the inhibition of p210$\rm\sp{bcr-abl}$ transforming activity by polypeptides interacting with p210$\rm\sp{bcr-abl}$ in murine myeloid 32D cells

The Bcr-Abl fusion oncogene which resulted from a balanced reciprocal translocation between chromosome 9 and 22, t(9;22)(q11, q34), encodes a 210 KD elevated tyrosine specific protein kinase that is found in more than 95 percent of chronic myelogenous leukemia patients (CML). Increase of level of phosphorylation of tyrosine is observed on cell cycle regulatory proteins in cells overexpressing the Bcr-Abl oncogene, which activates multiple signaling pathways. In addition, distinct signals are required for transforming susceptible fibroblast and hematopoietic cells, and the minimal signals essential for transforming hematopoietic cells are yet to be defined. In the present study, we first established a tetracycline repressible p210$\rm\sp{bcr-abl}$ expression system in a murine myeloid cell line 32D c13, which depends on IL3 to grow in the presence of tetracycline and proliferate independent of IL3 in the absence of tetracycline. Interestingly, one of these sublines does not form tumors in athymic nude mice suggesting that these cells may not be completely transformed. These cells also exhibit a dose-dependent growth and expression of p210$\rm\sp{bcr-abl}$ at varying concentrations of tetracycline in the culture. However, p210$\rm\sp{bcr-abl}$ rescues IL3 deprivation induced apoptosis in a non-dose dependent fashion. DNA genotoxic damage induced by gamma-irradiation activates c-Abl tyrosine kinase, the cellular homologue of p210$\rm\sp{bcr-abl},$ and leads to activation of p38 MAP kinase in the cells. However, in the presence of p210$\rm\sp{bcr-abl}$ the irradiation failed to activate the p38 MAP kinase as examined by an antibody against phosphorylated p38 MAP kinase. Similarly, an altered tyrosine phosphorylation of the JAK1-STAT1 pathways was identified in cells constitutively overexpressing p210$\rm\sp{bcr-abl}.$ This may provided a molecular mechanism for altered therapeutic response of CML patients to IFN-$\alpha.$^ Bcr-Abl oncoprotein has multiple functional domains which have been identified by the work of others. The Bcr tetramerization domain, which may function to stabilize the association of the Bcr-Abl with actin filaments in p210$\rm\sp{bcr-abl}$ susceptible cells, are essential for transforming both fibroblast and hematopoietic cells. We designed a transcription unit encoding first 160 amino acids polypeptide of Bcr protein to test if this polypeptide can inhibit the transforming activity of the p210$\rm\sp{bcr-abl}$ oncoprotein in the 32D c13 cells. When this vector was transfected transiently along with the p210$\rm\sp{bcr-abl}$ expression vector, it can block the transforming activity of p210$\rm\sp{bcr-abl}.$ On the other hand, the retinoblastoma tumor suppressor protein (Rb), a naturally occurring negative regulator of the c-Abl kinase, the cellular homologue of Bcr-Abl oncoprotein, binds to and inhibits the c-Abl kinase in a cell cycle dependent manner. A polypeptide obtained from the carboxyl terminal end of the retinoblastoma tumor suppressor protein, in which the nuclear localization signal was mutated, was used to inhibit the kinase activity of the p210$\rm\sp{bcr-abl}$ in the cytoplasm. This polypeptide, called Rb MC-box, and its wild type form, Rb C-box, when overexpressed in the 32D cells are mainly localized in the cytoplasm. Cotransfection of a plasmid transcription unit coding for this polypeptide and the gene for the p210$\rm\sp{bcr-abl}$ resulted in reduced plating efficiency of p210$\rm\sp{bcr-abl}$ transfected IL3 independent 32D cells. Together, these results may lead to a molecular approach to therapy of CML and an in vitro assay system to identify new targets to which an inhibitory polypeptide transcription unit may be directed. ^

Adaptation to Changes in the Coffee Value Chain and the Price of Coiffee among Coffee Producers in Two Villages in Kilimanjaro, Tanzania

Market liberalization in Tanzania has eroded the monopoly of the cooperative unions by allowing private coffee buyers (PCBs) to compete with them on equal footing. Similarly, farmers groups and primary societies are now allowed to sell coffee at auction. Thus, farmers have various options for selling their coffee. Similarly, the coffee industry has experienced large fluctuations in prices and stagnation in production. How do farmers react to these changes? Can and do farmers profit from different market conditions and sell to different traders at the lower end of the value chain, or do they remain with cooperatives or farmers groups? This study was conducted in Mruwia and Mshiri villages in Moshi Rural district. Whereas Mshiri village remains attached to the Kilimanjaro Native Cooperative Union (KNCU), Mruwia has detached from this organization and sells coffee independently. The sample (103) was randomly selected from the coffee farmers in the two villages. Data were collected through surveys, focus group discussions (FGDs), and socio-anthropological methods (participant-observation, biographies, and thematic interviews). Results indicate that the selection of whom to sell coffee depends largely on farmers’ dependence on coffee and prices, other benefits accrued, and whether the initial costs are covered by buyers. Additionally, most respondents did not sell coffee to PCBs. Thus, prices, the institutional infrastructure, and the structure of local communities were important when making decisions about how and with whom to trade.

Delivery of health care at the end of life in cancer patients of four swiss cantons a retrospective database study (SAKK 89/09)

Background The use of cancer related therapy in cancer patients at the end-of-life has increased over time in many countries. Given a lack of published Swiss data, the objective of this study was to describe delivery of health care during the last month before death of cancer patients. Methods Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating cantons), deceased between 2006-2008. Primary endpoints were hospitalization rate and delivery of cancer related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of patient and geographic characteristics. Results 3809 identified cancer patients were included. Hospitalization rate (mean 68.5%, 95%CI 67.0-69.9) and percentage of patients receiving anti-cancer drug therapies (ACDT, mean 14.5%, 95%CI 13.4-15.6) and radiotherapy (mean 7.7%, 95%CI 6.7-8.4) decreased with age. Canton of residence and insurance type status most significantly influenced the odds for hospitalization or receiving ACDT. Conclusions The intensity of cancer specific care showed substantial variation by age, cancer type, place of residence and insurance type status. This may be partially driven by cultural differences within Switzerland and the cantonal organization of the Swiss health care system.

Engagement in adolescent career preparation: Social support, personality, and the development of choice decidedness and congruence

This longitudinal panel study investigated predictors and outcomes of active engagement in career preparation among 349 Swiss adolescents from the beginning to the end of eighth grade. Latent variable structural equation modeling was applied. The results showed that engagement in terms of self- and environmental-exploration and active career planning related positively to interindividual increases in career decidedness and choice congruence. More perceived social support, early goal decidedness, and particular personality traits predicted more engagement. Support and personality impacted outcomes only mediated through engagement. Early decidedness and congruence were significant predictors of their respective later levels. Implications for practice are presented.

Cancer-related therapies at the end of life in hospitalized cancer patients from four Swiss cantons: SAKK 89/09.

The use of cancer-related therapies in cancer patients hospitalized at the end of life has increased in many countries over time. Given the scarcity of published Swiss data, the objective of this study was to evaluate the influence of hospital type and other factors on the delivery of health care during the last month before death. Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating Swiss cantons) who deceased between 2006 and 2008. Primary endpoints were delivery of cancer-related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of hospital type, patient and geographic characteristics. Of 3,809 identified cancer patients in the claims database, 2,086 patients dying from cancer were hospitalized during the last 30 days before death, generating 2,262 inpatient episodes. Anticancer drug therapy was given in 22.2% and radiotherapy in 11.7% of episodes. Besides age and cancer type, the canton of residence and hospital type showed independent, statistically significant associations with intensity of care, which was highest in university hospitals. These results should initiate a discussion among oncologists in Switzerland and may question the compliance with standard of care guidelines for terminal cancer patients.

Unique Sm core structure of U7 snRNPs: assembly by a specialized SMN complex and the role of a new component, Lsm11, in histone RNA processing.

A set of seven Sm proteins assemble on the Sm-binding site of spliceosomal U snRNAs to form the ring-shaped Sm core. The U7 snRNP involved in histone RNA 3' processing contains a structurally similar but biochemically unique Sm core in which two of these proteins, Sm D1 and D2, are replaced by Lsm10 and by another as yet unknown component. Here we characterize this factor, termed Lsm11, as a novel Sm-like protein with apparently two distinct functions. In vitro studies suggest that its long N-terminal part mediates an important step in histone mRNA 3'-end cleavage, most likely by recruiting a zinc finger protein previously identified as a processing factor. In contrast, the C-terminal part, which comprises two Sm motifs interrupted by an unusually long spacer, is sufficient to assemble with U7, but not U1, snRNA. Assembly of this U7-specific Sm core depends on the noncanonical Sm-binding site of U7 snRNA. Moreover, it is facilitated by a specialized SMN complex that contains Lsm10 and Lsm11 but lacks Sm D1/D2. Thus, the U7-specific Lsm11 protein not only specifies the assembly of the U7 Sm core but also fulfills an important role in U7 snRNP-mediated histone mRNA processing.

Timing of retreat of the Reuss Glacier (Switzerland) at the end of the Last Glacial Maximum

We used cosmogenic 10Be and 36Cl to establish the timing of the onset of deglaciation after the Last Glacial Maximum of the Reuss Glacier, one of the piedmont lobes of the Alpine ice cap that reached the northern Alpine foreland in Switzerland. In this study, we sampled erratic boulders both at the frontal position in the foreland (Lenzburg and Wohlen, canton Aargau) and at the lateral Alpine border position (Seeboden moraine, Rigi, canton Schwyz). The minimum age for the beginning of retreat is 22.2 ± 1.0 ka at the frontal (terminal) position and 20.4 ± 1.0 ka at the lateral position. These ages are directly comparable with exposure ages from the other piedmont lobes in the northern Alpine foreland. Our data from the mountain called Rigi, do not support the hypothesis that boulders located external to the Seeboden moraine were deposited prior to the last glacial cycle. We present a first exposure age from an erratic boulder in a retreat position in the Alpine foreland. The Reuss Glacier was approximately 12 km behind the maximal extent no later than at 18.6 ± 0.9 ka.

From Personal Network to Institution Building: The Lifanyuan and the Formalization of Manchu-Mongol Relations

The Qing emperors, who ruled over China from 1644-1911, managed to bring large parts of Inner Asia under their control and extended the territory of China to an unprecedented degree. This paper maintains that the political technique of patronage with its formalized language, its emphasis on gift exchange and expressions of courtesy is a useful concept for explaining the integration of Inner Asian confederations into the empire. By re-interpreting the obligations of gift exchange, the Qing transformed the network of personal relationships, which had to be reinforced and consolidated permanently into a system with clearly defined rules. In this process of formalization, the Lifanyuan, the Court for the Administration of the Outer Regions, played a key role. While in the early years of the dynasty, it was responsible for collecting and disseminating information concerning the various patronage relationships with Inner Asian leaders, over the course of the 17th and 18th centuries its efforts were directed at standardizing and streamlining the contacts between ethnic minorities and the state. Through the Lifanyuan, the rules and principles of patronage were maintained in a modified form even in the later part of the dynasty, when the Qing exercised control in the outer regions more directly. The paper provides an explanation for the longevity and cohesiveness of the multi-ethnic Qing empire. Based on recently published Manchu and Mongolian language archival material and the Maussian concept of gift exchange the study sheds new light on the changing self-conception of the Qing emperors.

Days spent in acute care hospitals at the end of life of cancer patients in four Swiss cantons: a retrospective database study (SAKK 89/09).

Number of days spent in acute hospitals (DAH) at the end of life is regarded as an important care quality indicator for cancer patients. We analysed DAH during 90 days prior to death in patients from four Swiss cantons. Claims data from an insurance provider with about 20% market share and patient record review identified 2086 patients as dying of cancer. We calculated total DAH per patient. Multivariable generalised linear modelling served to evaluate potential explanatory variables. Mean DAH was 26 days. In the multivariable model, using complementary and alternative medicine (DAH = 33.9; +8.8 days compared to non-users) and canton of residence (for patient receiving anti-cancer therapy, Zürich DAH = 22.8 versus Basel DAH = 31.4; for other patients, Valais DAH = 22.7 versus Ticino DAH = 33.7) had the strongest influence. Age at death and days spent in other institutions were additional significant predictors. DAH during the last 90 days of life of cancer patients from four Swiss cantons is high compared to most other countries. Several factors influence DAH. Resulting differences are likely to have financial impact, as DAH is a major cost driver for end-of-life care. Whether they are supply- or demand-driven and whether patients would prefer fewer days in hospital remains to be established.

Cystoscopy and the development of invasive bladder cancer in patients presenting with superficial urinary bladder cancer

The objective of this study was to determine the impact of different follow-up cystoscopy frequencies on time to development of invasive bladder cancer in a cohort of 3,658 eligible patients 65 and older with an initial diagnosis of superficial bladder cancer between 1994 and 1998. Bladder cancer patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database were used as the study population. ^ It was hypothesized that superficial bladder cancer patients receiving less frequent cystoscopy follow-up would develop invasive bladder cancer sooner after initial diagnosis and treatment than patients seen more frequently for cystoscopy follow-up. Cox Proportional Hazard Regression revealed that patients seen for cystoscopy every 3 or more months were 83–89% less likely to develop invasive cancer than patients seen every 1 to 2 months. A comparison of the 2 groups (1 to 2 months vs. 3≥ months) revealed that the 1 to 2 month group may have had more aggressive disease, and they are seen more frequently as a result. ^ These findings suggest that there are two groups of superficial bladder cancer patients: those at high risk of developing invasive bladder cancer and those at low risk. Patients who developed invasive bladder cancer sooner after initial diagnosis and treatment were seen more frequently for cystoscopy follow-up. The recommendation is that cystoscopy should be based on disease status at 3 months. Standardized schedules give all patients the same number of cystoscopies regardless of their risk factors. This could lead to unnecessary cystoscopies in low risk patients, and fewer than optimal cystoscopies in high risk patients. ^

"An attentive Ear, a watchful Eye, and a Calm judicious Pen": William Samuel Johnson, the Colonial Agents, and the Transformation of the British Atlantic World

By looking at Great Britain and the American colonies in conjunction with the larger British Atlantic Empire, historians can better understand the political, social, and cultural transformations that occurred when transatlantic actors met. William Samuel Johnson is an example of an "ordinary" agent who nonetheless had extensive contacts with numerous British and American thinkers. While acting on Connecticut's behalf in London between 1767 and 1771, he sent reports back to Connecticut governors Jonathan Trumbull and William Pitkin on parliamentary proceedings while corresponding with the people who traveled around the Atlantic world during this critical period-merchants, seafarers, emigrants, soldiers, missionaries, radicals and conservatives, reformers, and politicians. He is also representative of the late eighteenth-century empire writ large. Agents, who had once been a source of stability in the far-flung colonies, became a destabilizing force as confusion and conflict grew over conceptual ideas of what constituted "the empire" and who was included in it. Johnson was a sane observer in the midst of the ideological and administrative upheaval of the 1760's and 1770's. His subsequent loyalism and political obscurity during the war years was in many ways a result of his attempts to reconcile various factional interests during his tenure as an agent. Although he did his best to resolve these divisions and provide an accurate account of the powerful nationalistic forces gathering on both sides of the Atlantic on the eve of the American Revolution, the agents' collective failures as transatlantic mediators helped bring about the collapse of an imperial community. This disintegration had dramatic effects on the whole of the Atlantic world.