CA 125 regression after two completed cycles of chemotherapy: lack of prediction for long-term survival in patients with advanced ovarian cancer

The prognostic influence of CA 125 regression between the time point before surgery and after two completed courses of chemotherapy was studied in 210 patients with advanced ovarian cancer, and was compared to other well established prognostic factors. CA 125 blood samples were collected preoperatively (CA 125 pre) and 3 months after surgery (CA 125 3 mo) (at the beginning of the 3rd cycle of chemotherapy). The parameter CA 125 regression defined as log10 (CA 125 3 mo/CA 125 pre) was used for statistical analysis. In a survival analysis using a Cox proportional hazards model, CA 125 regression (P = 0.0001), residual tumour (P = 0.0001), age (P = 0.0095) and grading (P = 0.044) were independent variables, whereas stage of disease, histology, ascites and type of surgery failed to retain significance. Using log10 (CA 125 3 mo/CA 125 pre) as simple covariate in a Cox model showed a hazard ratio of 1.70 (95% confidence interval 1.32–2.19, P = 0.0001). However, a detailed analysis of the interaction of time with the prognostic factor CA 125 regression on survival revealed a strong time-dependent effect with a hazard ratio of more than 6 immediately after two courses of chemotherapy, whereas within approximately 1 year the hazard ratio for the surviving patients dropped quickly to the neutral level of 1. In summary, CA 125 regression is an independent prognostic factor for survival of women with advanced ovarian cancer and allows an identification of a high-risk population among patients with advanced ovarian cancer. However, the discriminating power of serial CA 125 for long-term survival seems to be temporary and prediction of individual patients outcome is far less precise. © 1999 Cancer Research Campaig

The Impact of Openness on Value Co-creation in Production Networks

AbstractThe increasing number and economic importance of production networks is one sign of the on-going paradigm shift from industrial production to value co-creation. This transformation can be described by using the notions of a value creation taxonomy, which is introduced in this paper and gives a structured overview of relevant aspects of the underlying conversion from top down to bottom up economics. In order to gain a deeper understanding of this transformation process, the specific design, characteristics and challenges of those networks will be investigated with regard to their time-dependence using a life cycle model.The present study contributes to a fundamental understanding of the importance of openness as a key success factor of value co-creation in production networks. It gives a systematic characterization of what is meant by “openness” concerning the value creation system, the value creation process and the value creation artifact. Furthermore, an adjusted life cycle model is presented, which may support both, assessment and configuration of openness within those networks by deriving adequate and phase-specific measures

Optimizing the phenotyping of rodent ASD models: enrichment analysis of mouse and human neurobiological phenotypes associated with high-risk autism genes identifies morphological, electrophysiological, neurological, and behavioral features

<p>Abstract</p> <p>Background</p> <p>There is interest in defining mouse neurobiological phenotypes useful for studying autism spectrum disorders (ASD) in both forward and reverse genetic approaches. A recurrent focus has been on high-order behavioral analyses, including learning and memory paradigms and social paradigms. However, well-studied mouse models, including for example <it>Fmr1 </it>knockout mice, do not show dramatic deficits in such high-order phenotypes, raising a question as to what constitutes useful phenotypes in ASD models.</p> <p>Methods</p> <p>To address this, we made use of a list of 112 disease genes etiologically involved in ASD to survey, on a large scale and with unbiased methods as well as expert review, phenotypes associated with a targeted disruption of these genes in mice, using the Mammalian Phenotype Ontology database. In addition, we compared the results with similar analyses for human phenotypes.</p> <p>Findings</p> <p>We observed four classes of neurobiological phenotypes associated with disruption of a large proportion of ASD genes, including: (1) Changes in brain and neuronal morphology; (2) electrophysiological changes; (3) neurological changes; and (4) higher-order behavioral changes. Alterations in brain and neuronal morphology represent quantitative measures that can be more widely adopted in models of ASD to understand cellular and network changes. Interestingly, the electrophysiological changes differed across different genes, indicating that excitation/inhibition imbalance hypotheses for ASD would either have to be so non-specific as to be not falsifiable, or, if specific, would not be supported by the data. Finally, it was significant that in analyses of both mouse and human databases, many of the behavioral alterations were neurological changes, encompassing sensory alterations, motor abnormalities, and seizures, as opposed to higher-order behavioral changes in learning and memory and social behavior paradigms.</p> <p>Conclusions</p> <p>The results indicated that mutations in ASD genes result in defined groups of changes in mouse models and support a broad neurobiological approach to phenotyping rodent models for ASD, with a focus on biochemistry and molecular biology, brain and neuronal morphology, and electrophysiology, as well as both neurological and additional behavioral analyses. Analysis of human phenotypes associated with these genes reinforced these conclusions, supporting face validity for these approaches to phenotyping of ASD models. Such phenotyping is consistent with the successes in <it>Fmr1 </it>knockout mice, in which morphological changes recapitulated human findings and electrophysiological deficits resulted in molecular insights that have since led to clinical trials. We propose both broad domains and, based on expert review of more than 50 publications in each of the four neurobiological domains, specific tests to be applied to rodent models of ASD.</p

Comment on the Definition of Eligible Organization for Purposes of Coverage of Certain Preventive Services Under the Affordable Care Act

This comment letter was submitted by U.C. Berkeley corporate law professors in response to a request for comment by the Health and Human Services Department on the definition of eligible organization under the Affordable Care Act in light of the Supreme Court\u27s decision in Burwell v. Hobby Lobby. Eligible organizations will be permitted under the Hobby Lobby decision to assert the religious principles of their shareholders to exempt themselves from the Affordable Care Act\u27s contraceptive mandate for employees. In Hobby Lobby, the Supreme Court held that the nexus of identity between several closely-held, for-profit corporations and their shareholders holding “a sincere religious belief that life begins at conception” was sufficiently close to justify granting such corporations an exemption from the Affordable Care Act\u27s contraceptive mandate pursuant to the Religious Freedom Restoration Act of 1993. More specifically, the Court ascertained that the overall interests of the corporations and their natural-person shareholders were sufficiently identical to warrant ascribing the religious commitments of the shareholders to their corporations. Notably, the Court stopped short of articulating a diagnostic test for determining when a sufficient overlap of interests exists; instead, it concluded that well-established principles in state corporate law should provide such guidance. We believe that state corporate law does in fact provide the diagnostic test the Court desires for determining when it is appropriate to disregard the distinct identity of a corporation for the identity of its shareholders. This test is rooted in the long-standing case law that constitutes the alter ego doctrine (commonly referred to as “veil piercing”). To sustain a claim of veil piercing, state corporate law uniformly requires there to be “unity of ownership and interest” between the corporation and its shareholders. If a corporation is operated as the effective alter ego of its shareholders to such an extent that its separate corporate existence ceases to exist as a practical matter, then a veil piercing claim can be established that effectively attributes the corporation’s legal rights and obligations to its shareholders, and vice versa. A veil piercing conclusion effectively holds that there is no practical difference between the corporation and the shareholders themselves. We therefore propose that for purposes of defining an “eligible organization” under Hobby Lobby, the HHS and other federal organizations should follow the corporate law doctrine of veil piercing. Indeed, to make this doctrine administratively feasible, we further suggest that shareholders of a corporation should have to certify that they and the corporation have a unity in identity and interests, and therefore the corporation should be viewed as the shareholders’ alter ego

A deficit of spatial remapping in constructional apraxia after right-hemisphere stroke

This Article is provided by the Brunel Open Access Publising Fund - Copyright @ 2010 Oxford University PressConstructional apraxia refers to the inability of patients to copy accurately drawings or three-dimensional constructions. It is a common disorder after right parietal stroke, often persisting after initial problems such as visuospatial neglect have resolved. However, there has been very little experimental investigation regarding mechanisms that might contribute to the syndrome. Here, we examined whether a key deficit might be failure to integrate visual information correctly from one fixation to the next. Specifically, we tested whether this deficit might concern remapping of spatial locations across saccades. Right-hemisphere stroke patients with constructional apraxia were compared to patients without constructional problems and neurologically healthy controls. Participants judged whether a pattern shifted position (spatial task) or changed in pattern (non-spatial task) across two saccades, compared to a control condition with an equivalent delay but without intervening eye movements. Patients with constructional apraxia were found to be significantly impaired in position judgements with intervening saccades, particularly when the first saccade of the sequence was to the right. The importance of these remapping deficits in constructional apraxia was confirmed through a highly significant correlation between saccade task performance and constructional impairment on standard neuropsychological tasks. A second study revealed that even single saccades to the right can impair constructional apraxia patients’ perception of location shifts. These data are consistent with the view that rightward eye movements result in loss of remembered spatial information from previous fixations, presumably due to constructional apraxia patients’ damage to the right-hemisphere regions involved in remapping locations across saccades. These findings provide the first evidence for a deficit in remapping visual information across saccades underlying right-hemisphere constructional apraxia.European Commission Marie Curie Intra-European Fellowship (011457 to C.R.) and a Wellcome Trust Senior Fellowship (to M.H.)

On the Role of Object Information in Action Observation: An fMRI Study

Observing other people’s actions activates a network of brain regions that is also activated during the execution of these actions. Here, we used functional magnetic resonance imaging to test whether these “mirror” regions in frontal and parietal cortices primarily encode the spatiomotor aspects or the functional goal-related aspects of observed tool actions. Participants viewed static depictions of actions consisting of a tool object (e.g., key) and a target object (e.g., keyhole). They judged the actions either with regard to whether the objects were oriented correctly for the action to succeed (spatiomotor task) or whether an action goal could be achieved with the objects (function task). Compared with a control condition, both tasks activated regions in left frontoparietal cortex previously implicated in action observation and execution. Of these regions, the premotor cortex and supramarginal gyrus were primarily activated during the spatiomotor task, whereas the middle frontal gyrus was primarily activated during the function task. Regions along the intraparietal sulcus were more strongly activated during the spatiomotor task but only when the spatiomotor properties of the tool object were unknown in advance. These results suggest a division of labor within the action observation network that maps onto a similar division previously proposed for action execution