Cryoablation for breast cancer: No need to turn a cold shoulder

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58550/1/20887_ftp.pd

Pros and Cons of Adjuvant Interferon in the Treatment of Melanoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139970/1/onco0451.pd

A Constitution of Democratic Experimentalism

In this Article, Professors Dorf and Sabel identify a new form of government, democratic experimentalism, in which power is decentralized to enable citizens and other actors to utilize their local knowledge to fit solutions to their individual circumstances, but in which regional and national coordinating bodies require actors to share their knowledge with others facing similar problems. This information pooling, informed by the example of novel kinds of coordination within and among private firms, both increases the efficiency of public administration by encouraging mutual learning among its parts and heightens its accountability through participation of citizens in the decisions that affect them. In democratic experimentalism, subnational units of government are broadly free to set goals and to choose the means to attain them. Regulatory agencies set and ensure compliance with national objectives by means of bestpractice performance standards based on information that regulated entities provide in return for the freedom to experiment with solutions they prefer. The authors argue that this type of self-government is currently emerging in settings as diverse as the regulation of nuclear power plants, community policing, procurement of sophisticated military hardware, environmental regulation, and child-protective services. The Article claims further that a shift towards democratic experimentalism holds out the promise of reducing the distance between, on the one hand, the Madisonian ideal of a limited government assured by a complex division of powers and, on the other hand, the governmental reality characteristic of the New Deal synthesis, in which an all-powerful Congress delegates much of its authority to expert agencies that are checked by the courts when they infringe individual rights, but are otherwise assumed to act in the public interest. Professors Dorf and Sabel argue that the combination of decentralization and mutual monitoring intrinsic to democratic experimentalism better protects the constitutional ideal than do doctrines of federalism and the separation of powers, so at odds with current circumstances, that courts recognize the futility of applying them consistently in practice by limiting themselves to fitful declarations of their validity in principle. For example, conventional administrative law imposes external judicial checks on administrative agencies, obliging judges to choose between superficial scrutiny of formal proprieties and disruptive, indeed often paralyzing, inquiry into what an idealized agency might be expected to do. By contrast, democratic experimentalism requires the social actors, separately and in exchange with each other, to take constitutional considerations into account in their decisionmaking. The administrative agency assists the actors even while monitoring their performance by scrutinizing the reactions of each to relevant proposals by the others. The courts then determine whether the agency has met its obligations to foster and generalize the results of this information pooling. Agencies and courts alike use the rich record of the parties\u27 intentions, as interpreted by their acts contained in the continuing, comparative evaluation of experimentation itself In the administrative and related settings, the aim of democratic experimentalism is to democratize public decisionmaking from within, and so lessen the burdens on a judiciary that today awkwardly superintends the every-day workings of democracy from an external vantage point. Finally, the Article reconceptualizes constitutional rights. Relying in this and other regards on ideas associated with early-twentieth-century American pragmatism, the Article treats disagreements over rights as principally about how to implement widely shared general principles. Under the heading of prophylactic rules and related doctrines, the United States Supreme Court has recognized that there are often a variety of acceptable remedies for a violation of rights or a variety of acceptable means of achieving a constitutionally mandated end. The authors argue for a radical extension of these doctrines, in which judicial recognition of a general, core right, permits substantial experimentation about how to implement that right. They propose institutional mechanisms to facilitate such experimentation. The authors contend, however, that with rights, as with other constitutionally entrenched principles, means and ends cannot be neatly separated, so that experimentation at the periphery also redefines the core, ultimately challenging the very distinction between core and periphery

Drug Treatment Courts and Emergent Experimentalist Government

Despite the continuing war on drugs, the last decade has witnessed the creation and nationwide spread of a remarkable set of institutions, drug treatment courts. In drug treatment court, a criminal defendant pleads guilty or otherwise accepts responsibility for a charged offense and accepts placement in a court-mandated program of drug treatment. The judge and court personnel closely monitor the defendant\u27s performance in the program and the program\u27s capacity to serve the mandated client. The federal government and national associations in turn monitor the local drug treatment courts and disseminate successful practices. The ensemble of institutions, monitoring, and pooling exemplifies what the authors have elsewhere called experimentalism. The authors argue here that treatment courts as open and evolving experimentalist institutions point one way beyond the conventional limitations of courts and other oversight institutions. By pooling information on good and bad performance, and sanctioning when necessary unsatisfactory performers, the courts enable and oblige improvement by the actors both individually and as members of a complex ensemble. Judicial involvement in reform is permanent and continuous in this model. Yet it is, paradoxically, less imperious than traditional methods of court-directed reform for two reasons. First, the court in effect compels the actors to learn continuously and incrementally from each other rather than instructing them to implement a comprehensive remedial plan devised by the court alone or even in consultation with the parties. Second, the court is itself compelled to change in response to the changes it facilitates. In part this occurs through the exchanges with the treatment providers and in part it occurs in response to comparisons with experience in other jurisdictions as revealed by national pooling. Thus, the article argues, the experimentalist architecture of the drug courts suggests that they and like institutions need not face a strict tradeoff between efficacy and accountability

Drug Treatment Courts and Emergent Experimental Government

Despite the continuing war on drugs, the last decade has witnessed the creation and nationwide spread of a remarkable set of institutions, drug treatment courts. In drug treatment court, a criminal defendant pleads guilty or otherwise accepts responsibility for a charged offense and accepts placement in a court-mandated program of drug treatment. The judge and court personnel closely monitor the defendant\u27s performance in the program and the program\u27s capacity to serve the mandated client. The federal government and national associations in turn monitor the local drug treatment courts and disseminate successful practices. The ensemble of institutions, monitoring, and pooling exemplifies what the authors have elsewhere called experimentalism. The authors argue here that treatment courts as open and evolving experimentalist institutions point one way beyond the conventional limitation of courts and other institutions. By pooling information on good and bad performance, and sanctioning when necessary unsatisfactory performers, the courts enable and oblige improvement by the actors both individually and as members of a complex ensemble. Judicial involvement in reform is permanent and continuous in this model. Yet it is, paradoxically, less imperious than traditional methods of court-directed reform for two reasons. First, the court in effect compels the actors to learn continuously and incrementally from each other rather than instructing them to implement a comprehensive remedial plan devised by the court alone or even in consultation with the parties. Second, the court is itself compelled to change in response to the changes it facilitates. In part this occurs through the exchanges with the treatment providers and in part it occurs in response to comparisons with experience in other jurisdictions as revealed by national pooling. Thus, the article argues, the experimentalist architecture of the drug courts suggests that they and like institutions need not face a strict tradeoff between efficacy and accountability

A Constitution of Democratic Experimentalism

In this Article, Professors Dorf and Sabel identify a new form of government, democratic experimentalism, in which power is decentralized to enable citizens and other actors to utilize their local knowledge to fit solutions to their individual circumstances, but in which regional and national coordinating bodies require actors to share their knowledge with others facing similar problems. This information pooling, informed by the example of novel kinds of coordination within and among private firms, both increases the efficiency of public administration by encouraging mutual learning among its parts and heightens its accountability through participation of citizens in the decisions that affect them. In democratic experimentalism, subnational units of government are broadly free to set goals and to choose the means to attain them. Regulatory agencies set and ensure compliance with national objectives by means of best-practice performance standards based on information that regulated entities provide in return for the freedom to experiment with solutions they prefer. The authors argue that this type of self-government is currently emerging in settings as diverse as the regulation of nuclear power plants, community policing, procurement of sophisticated military hardware, environmental regulation, and child-protective services. The Article claims further that a shift towards democratic experimentalism holds out the promise of reducing the distance between, on the one hand, the Madisonian ideal of a limited government assured by a complex division of powers and, on the other hand, the governmental reality characteristic of the New Deal synthesis, in which an all-powerful Congress delegates much of its authority to expert agencies that are checked by the courts when they infringe individual rights, but are otherwise assumed to act in the public interest. Professors Dorf and Sabel argue that the combination of decentralization and mutual monitoring intrinsic to democratic experimentalism better protects the constitutional ideal than do doctrines of federalism and the separation of powers, so at odds with current circumstances, that courts recognize the futility of applying them consistently in practice by limiting themselves to fitful declarations of their validity in principle. For example, conventional administrative law imposes external judicial checks on administrative agencies, obliging judges to choose between superficial scrutiny of formal proprieties and disruptive, indeed often paralyzing, inquiry into what an idealized agency might be expected to do. By contrast, democratic experimentalism requires the social actors, separately and in exchange with each other, to take constitutional considerations into account in their decisionmaking. The administrative agency assists the actors even while monitoring their performance by scrutinizing the reactions of each to relevant proposals by the others. The courts then determine whether the agency has met its obligations to foster and generalize the results of this information pooling. Agencies and courts alike use the rich record of the parties\u27 intentions, as interpreted by their acts contained in the continuing, comparative evaluation of experimentation itself In the administrative and related settings, the aim of democratic experimentalism is to democratize public decisionmaking from within, and so lessen the burdens on a judiciary that today awkwardly superintends the every-day workings of democracy from an external vantage point. Finally, the Article reconceptualizes constitutional rights. Relying in this and other regards on ideas associated with early-twentieth-century American pragmatism, the Article treats disagreements over rights as principally about how to implement widely shared general principles. Under the heading of prophylactic rules and related doctrines, the United States Supreme Court has recognized that there are often a variety of acceptable remedies for a violation of rights or a variety of acceptable means of achieving a constitutionally mandated end. The authors argue for a radical extension of these doctrines, in which judicial recognition of a general, core right, permits substantial experimentation about how to implement that right. They propose institutional mechanisms to facilitate such experimentation. The authors contend, however, that with rights, as with other constitutionally entrenched principles, means and ends cannot be neatly separated, so that experimentation at the periphery also redefines the core, ultimately challenging the very distinction between core and periphery

Proteomics in Melanoma Biomarker Discovery: Great Potential, Many Obstacles

The present clinical staging of melanoma stratifies patients into heterogeneous groups, resulting in the application of aggressive therapies to large populations, diluting impact and increasing toxicity. To move to a new era of therapeutic decisions based on highly specific tumor profiling, the discovery and validation of new prognostic and predictive biomarkers in melanoma is critical. Genomic profiling, which is showing promise in other solid tumors, requires fresh tissue from a large number of primary tumors, and thus faces a unique challenge in melanoma. For this and other reasons, proteomics appears to be an ideal choice for the discovery of new melanoma biomarkers. Several approaches to proteomics have been utilized in the search for clinically relevant biomarkers, but to date the results have been relatively limited. This article will review the present work using both tissue and serum proteomics in the search for melanoma biomarkers, highlighting both the relative advantages and disadvantages of each approach. In addition, we review several of the major obstacles that need to be overcome in order to advance the field

Complement C3 serum levels in anorexia nervosa: a potential biomarker for the severity of disease?

BackgroundAnorexia nervosa carries the highest mortality rate of any psychiatric disorder. Even the most critically ill anorexic patients may present with normal 'standard' laboratory values, underscoring the need for a new sensitive biomarker. The complement cascade, a major component of innate immunity, represents a driving force in the pathophysiology of multiple inflammatory disorders. The role of complement in anorexia nervosa remains poorly understood. The present study was designed to evaluate the role of complement C3 levels, the extent of complement activation and of complement hemolytic activity in serum, as potential new biomarkers for the severity of anorexia nervosa.Patients and methodsThis was a prospective cohort study on 14 patients with severe anorexia nervosa, as defined by a body mass index (BMI) <14 kg/m2. Serum samples were obtained in a biweekly manner until hospital discharge. A total of 17 healthy subjects with normal BMI values served as controls. The serum levels of complement C3, C3a, C5a, sC5b-9, and of the 50% hemolytic complement activity (CH50) were quantified and correlated with the BMIs of patients and control subjects.ResultsSerum C3 levels were significantly lower in patients with anorexia nervosa than in controls (median 3.7 (interquartile range (IQR) 2.5-4.9) vs 11.4 (IQR 8.9-13.7, P <0.001). In contrast, complement activation fragments and CH50 levels were not significantly different between the two groups. There was a strong correlation between index C3 levels and BMI (Spearman correlation coefficient = 0.71, P <0.001).ConclusionsComplement C3 serum levels may represent a sensitive new biomarker for monitoring the severity of disease in anorexia nervosa. The finding from this preliminary pilot study will require further investigation in future prospective large-scale multicenter trials

A knee cannot have lung disease: out-of-distribution detection with in-distribution voting using the medical example of chest X-ray classification

Deep learning models are being applied to more and more use cases with astonishing success stories, but how do they perform in the real world? To test a model, a specific cleaned data set is assembled. However, when deployed in the real world, the model will face unexpected, out-of-distribution (OOD) data. In this work, we show that the so-called "radiologist-level" CheXnet model fails to recognize all OOD images and classifies them as having lung disease. To address this issue, we propose in-distribution voting, a novel method to classify out-of-distribution images for multi-label classification. Using independent class-wise in-distribution (ID) predictors trained on ID and OOD data we achieve, on average, 99 % ID classification specificity and 98 % sensitivity, improving the end-to-end performance significantly compared to previous works on the chest X-ray 14 data set. Our method surpasses other output-based OOD detectors even when trained solely with ImageNet as OOD data and tested with X-ray OOD images.Comment: Code available at https://gitlab.lrz.de/IP/a-knee-cannot-have-lung-diseas