Penalties and Optimality in Financial Contracts: Taking Stock

A popular view of limited liability in financial contracting is that it is the result of societal preferences against excessive penalties. The view of most financial economists is instead that limited liability emerged as an optimal institution when, in the absence of a clear limit on economic agents liability, the development of some economic activities might have been thwarted. Viewing the institution from the perspective of optimal legal system design allows us to better understand the current debate on it. We present a broad history of penalties in financial contracts to highlight the interactions between technology, legal environments, purpose of the financial relationship, and contractual provisions. We show that harsh monetary and non-pecuniary penalties are not mere relics from a bygone era and, at the same time, that limited liability is far from a recent institution. We then discuss trade-offs associated with legal mandates of either unlimited or limited liability, both for the contracting parties and for the rest of Society. We identify two broad patterns. First, the toughness of liability rules and bankruptcy laws decreases as exogenous sources of uncertainty become relatively more important, and increases with the opportunity for moral hazard (related to diligence, risk taking, or deception). Second, bankruptcy laws become more lenient as the scope for labor specialization and the returns to human capital or entrepreneurship increase.Limited Liability, Bankruptcy, Debt Bondage, Debtors' Prison, History

Концепция соотношения сознательного и стихийного В.И. Ленина: опыт оценки

В статье представлен опыт оценки концепции соотношения сознательного и стихийного В.И. Ленина. Его структуру определяет последовательность решения задач, которая обеспечивает установление достижений и недостатков концепции соотношения сознательного и стихийного В.И.Ленина в истолковании этого соотношения. Сначала выделяются компоненты, образующие структуру теории соотношения сознательного и стихийного; затем выясняется, каким образом они раскрываются в концепции В.И. Ленина; после этого указываются критерии, по которым могут оцениваться философские концепции, определенным образом истолковывающие соотношение сознательного и стихийного; в соответствии с установленными критериями дается оценка как концепции соотношения сознательного и стихийного В.И. Ленина в целом, так и ее отдельным компонентам. В заключение делаются выводы о тех отношениях, в которых рассмотренная концепция В.И. Ленина может быть оценена позитивно и негативно.In the article the experience of estimation of conception of the alignment of conscious and elemental of V.I. Lenin is presented. Experience's structure is determined by the sequence of decision of tasks, which provides establishment of the achievements and lacks of the conception of the alignment of conscious and elemental of V.I. Lenin in the interpretation of this alignment. The components which form the structure of the theory of alignment of conscious and elemental are designated at first; then it appears, how they are being revealed in V.I. Lenin's conception; after this the criteria on which philosophical conceptions can be estimated are indicated, definitely interpreting the alignment of conscious and elemental; in accordance with the established criteria the estimation is given both of conception of alignment conscious and elemental of V.I. Lenin as a whole, and of its separate components. Inferences about those relations in which the considered conception of V.I. Lenin can be appraised positively and negatively are drawn in conclusion

Serial FEM/XFEM-Based Update of Preoperative Brain Images Using Intraoperative MRI

Current neuronavigation systems cannot adapt to changing intraoperative conditions over time. To overcome this limitation, we present an experimental end-to-end system capable of updating 3D preoperative images in the presence of brain shift and successive resections. The heart of our system is a nonrigid registration technique using a biomechanical model, driven by the deformations of key surfaces tracked in successive intraoperative images. The biomechanical model is deformed using FEM or XFEM, depending on the type of deformation under consideration, namely, brain shift or resection. We describe the operation of our system on two patient cases, each comprising five intraoperative MR images, and we demonstrate that our approach significantly improves the alignment of nonrigidly registered images

A STAT3 Gene Expression Signature in Gliomas is Associated with a Poor Prognosis

Gliomas frequently display constitutive activation of the transcription factor STAT3, a protein that is known to be able to mediate neoplastic transformation. STAT3 regulates genes that play a central role in cellular survival, proliferation, self-renewal, and invasion, and a cohort of STAT3 target genes have been found that are commonly coexpressed in human cancers. Thus, these genes likely subserve the transforming ability of constitutively activated STAT3. To determine whether the coordinated expression of STAT3 target genes is present in a subset of human gliomas, and whether this changes the biology of these tumors in patients, gene expression analysis was performed in four distinct human glioma data sets for which patient survival information was available. Coordinate expression of STAT3 targets was significantly associated with poor patient outcome in each data set. Specifically, patients with tumors displaying high expression of STAT3 targets had a shorter median survival time compared to patients whose tumors had low expression of STAT3 targets. These data suggest that constitutively activated STAT3 in gliomas can alter the biology of these tumors, and that development of targeted STAT3 inhibitors would likely be of particular benefit in treatment of this disease

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23 февраля 2011 года исполнилось 75 лет со дня рождения главного инженера Днепродзержинской ГЭС — Кучерявого Владислава Семеновича.15 июня 2011 г. исполняется 70 лет ученому — гидроэнергетику, доктору технических наук, начальнику отдела расчетного обоснования ПАО "Укргидропроект", профессору, заведующему кафедрой гидротехнического строительства Харьковского государственного технического университета строительства и архитектуры Александру Исааковичу Вайнбергу

STAT5b is a marker of poor prognosis, rather than a therapeutic target in glioblastomas.

peer reviewedThe copy number and mRNA expression of STAT5b were assessed in samples from the TCGA repository of glioblastomas (GBM). The activation of this transcription factor was analyzed on tissue microarrays comprising 392 WHO 2016 GBM samples from our clinical practice. These data were correlated with patient survival using multivariable Cox analysis and, for a subset of 167 tumors, with signs of tumor invasiveness on the MRI. The effects of STAT5b knockdown by siRNA were assessed on the growth, therapeutic resistance, invasion and migration of GBM cell lines U87, U87‑EGFRVIII and LN18 and primary cultures GM2 and GM3. The activation, but not the copy number or the mRNA expression of nuclear transcription factor STAT5b expression correlated inversely with patient survival independently of IDH1R132H status, age, Karnofsky Performance Score, treatment and tumor volume. STAT5b inhibition neither altered the cell proliferation nor reduced the clonogenic proliferative potency of GBM cells, and did not sensitize them to the cytotoxic effect of ionizing radiation and temozolomide in vitro. STAT5b inhibition significantly increased GBM cell migration, but decreased the invasion of some GBM cells in vitro. There was no correlation between the activation of STAT5b in clinical tumors and the extent of invasion on MRI OF patients. In conclusion, STAT5b is frequently activated in GBM and correlates inversely with patient survival. It does not contribute to the growth and resistance of these tumors, and is thus rather a potential prognostic marker than a therapeutic target in these tumors

Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of Sulfasalazine for the treatment of progressing malignant gliomas in adults

BACKGROUND: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport inhibitor, has demonstrated a strong antitumoral potential in preclinical models of malignant gliomas. As it presents an excellent safety profile, we initiated a phase 1/2 clinical study of this anti-inflammatory drug for the treatment of recurrent WHO grade 3 and 4 astrocytic gliomas in adults. METHODS: 10 patients with advanced recurrent anaplastic astrocytoma (n = 2) or glioblastoma (n = 8) aged 32-62 years were recruited prior to the planned interim analysis of the study. Subjects were randomly assigned to daily doses of 1.5, 3, 4.5, or 6 grams of oral sulfasalazine, and treated until clinical or radiological evidence of disease progression or the development of serious or unbearable side effects. Primary endpoints were the evaluation of toxicities according to the CTCAE v.3.0, and the observation of radiological tumor responses based on MacDonald criteria. RESULTS: No clinical response was observed. One tumor remained stable for 2 months with sulfasalazine treatment, at the lowest daily dose of the drug. The median progression-free survival was 32 days. Side effects were common, as all patients developed grade 1-3 adverse events (mean: 7.2/patient), four patients developed grade 4 toxicity. Two patients died while on treatment or shortly after its discontinuation. CONCLUSION: Although the proper influence of sulfasalazine treatment on patient outcome was difficult to ascertain in these debilitated patients with a large tumor burden (median KPS = 50), ISRCTN45828668 was terminated after its interim analysis. This study urges to exert cautiousness in future trials of Sulfasalazine for the treatment of malignant gliomas. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45828668

Quantifying Risk Factors for Human Brucellosis in Rural Northern Tanzania

Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA) test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV) serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from livestock to humans. These can be achieved through health education to the communities where brucellosis is common