The problem of evaluating automated large-scale evidence aggregators

In the biomedical context, policy makers face a large amount of potentially discordant evidence from different sources. This prompts the question of how this evidence should be aggregated in the interests of best-informed policy recommendations. The starting point of our discussion is Hunter and Williams’ recent work on an automated aggregation method for medical evidence. Our negative claim is that it is far from clear what the relevant criteria for evaluating an evidence aggregator of this sort are. What is the appropriate balance between explicitly coded algorithms and implicit reasoning involved, for instance, in the packaging of input evidence? In short: What is the optimal degree of ‘automation’? On the positive side: We propose the ability to perform an adequate robustness analysis as the focal criterion, primarily because it directs efforts to what is most important, namely, the structure of the algorithm and the appropriate extent of automation. Moreover, where there are resource constraints on the aggregation process, one must also consider what balance between volume of evidence and accuracy in the treatment of individual evidence best facilitates inference. There is no prerogative to aggregate the total evidence available if this would in fact reduce overall accuracy

Evaluating competing theories via a common language of qualitative verdicts

Kuhn (The essential tension—Selected studies in scientific tradition and change, 1977) claimed that several algorithms can be defended to select the best theory based on epistemic values such as simplicity, accuracy, and fruitfulness. In a recent paper, Okasha (Mind 129(477):83–115, 2011) argued that no theory choice algorithm exists which satisfies a set of intuitively compelling conditions that Arrow (Social choice and individual values, 1963) had proposed for a consistent aggregation of individual preference orderings. In this paper, we put forward a solution to avoid this impossibility result. Based on previous work by Gaertner and Xu (Mathematical Social Sciences 63:193–196, 2012), we suggest to view the theory choice problem in a cardinal context and to use a general scoring function defined over a set of qualitative verdicts for every epistemic value. This aggregation method yields a complete and transitive ranking and the rule satisfies all Arrovian conditions appropriately reformulated within a cardinal setting. We also propose methods that capture the aggregation across different scientists

The problem of evaluating automated large-scale evidence aggregators

In the biomedical context, policy makers face a large amount of potentially discordant evidence from different sources. This prompts the question of how this evidence should be aggregated in the interests of best-informed policy recommendations. The starting point of our discussion is Hunter and Williams’ recent work on an automated aggregation method for medical evidence. Our negative claim is that it is far from clear what the relevant criteria for evaluating an evidence aggregator of this sort are. What is the appropriate balance between explicitly coded algorithms and implicit reasoning involved, for instance, in the packaging of input evidence? In short: What is the optimal degree of ‘automation’? On the positive side: We propose the ability to perform an adequate robustness analysis (which depends on the nature of the input variables and parameters of the aggregator) as the focal criterion, primarily because it directs efforts to what is most important, namely, the structure of the algorithm and the appropriate extent of automation. Moreover, where there are resource constraints on the aggregation process, one must also consider what balance between volume of evide

Robustness, evidence, and uncertainty: an exploration of policy applications of robustness analysis

Policy-makers face an uncertain world. One way of getting a handle on decision-making in such an environment is to rely on evidence. Despite the recent increase in post-fact figures in politics, evidence-based policymaking takes centre stage in policy-setting institutions. Often, however, policy-makers face large volumes of evidence from different sources. Robustness analysis can, prima facie, handle this evidential diversity. Roughly, a hypothesis is supported by robust evidence if the different evidential sources (such as observations or model results) are in agreement. In this thesis, I strengthen the case for the use of robustness analysis in evidence-based policymaking by answering open research questions about this inference technique. First, I argue that existing taxonomies miss a fruitful category of robustness reasoning, that is predictive stability. Second, I claim that derivational robustness analysis – the investigation of whether the results of different models are in agreement – can yield interesting insights even if not the entire relevant model space is covered by available models or if the model results are only partially in agreement. Third, I claim that expert knowledge is necessary to address questions that arise when one applies measurement robustness analysis – the investigation into whether multiple means of measurement yield the same result. Finally, I argue that, in situations where evidence from different measurements is not in agreement, it can be advisable to no longer take all of the evidence into account. This can be done in a rationally defensible way by choosing the most adequate theory or model underlying parts of the evidence set. I discuss examples from climate, medical, and economic policy-making to establish my claims

Inkommensurabilität – Implikationen für die evolutionäre Organisationstheorie unter begriffstheoretischer und epistemologischer Perspektive

Innerhalb der Organisationstheorie ist ein Theoriepluralismus zu konstatieren, der sich in einer Vielzahl unterschiedlicher Erklärungsansätze und Konzeptualisierungen des Verhaltens betriebswirtschaftlich organisierter Unternehmen äussert. Drehund Angelpunkt für die Beantwortung der Frage, wie dieser Theoriepluralismus zu bewerten ist, bildet der Begriff der Inkommensurabilität. Die vorliegende Untersuchung nimmt sich dieser Thematik an. In einem ersten Schritt wird der Begriff der Inkommensurabilität analysiert. Zielpunkt dieser Begriffsklärung ist ein metatheoretischer Bezugsrahmen, der mit einer begriffstheoretischen und einer epistemologischen Bedingung ein Kriterienpaket bereithält, welches die Grundlagen der Inkommensurabilität sicht- und handhabbar macht. Anhand dieses Bezugsrahmens werden in einem zweiten Schritt exemplarisch Implikationen der Inkommensurabilitätsthematik für die evolutionäre Organisationstheorie dargelegt. Die Implikationen werden in Form von acht inter- und intratheoretischen Befunden erläutert.Diese Argumentationslinie ermöglicht abschliessend eine reflektierte Einschätzung des Theoriepluralismus und die Exponierung einer neuen Forschungsstrategie für die Grundlagendebatte in der Organisationstheorie.Keywords: Theoriepluralismus, Inkommensurabilität, Thomas S. Kuhn, Evolutionäre Organisationstheori

The problem of evaluating automated large-scale evidence aggregators

In the biomedical context, policy makers face a large amount of potentially discordant evidence from different sources. This prompts the question of how this evidence should be aggregated in the interests of best-informed policy recommendations. The starting point of our discussion is Hunter and Williams’ recent work on an automated aggregation method for medical evidence. Our negative claim is that it is far from clear what the relevant criteria for evaluating an evidence aggregator of this sort are. What is the appropriate balance between explicitly coded algorithms and implicit reasoning involved, for instance, in the packaging of input evidence? In short: What is the optimal degree of ‘automation’? On the positive side: We propose the ability to perform an adequate robustness analysis (which depends on the nature of the input variables and parameters of the aggregator) as the focal criterion, primarily because it directs efforts to what is most important, namely, the structure of the algorithm and the appropriate extent of automation. Moreover, where there are resource constraints on the aggregation process, one must also consider what balance between volume of evidence and accuracy in the treatment of individual evidence best facilitates inference. There is no prerogative to aggregate the total evidence available if this would in fact reduce overall accuracy

Immunolocalization of phospho-S6 kinases: a new way to detect mitosis in tissue sections and in cell culture

During a study on the mTor pathway in the rat kidney we observed a striking increase of the phosphorylation of the S6 kinase in mitosis. In cryostat sections of perfusion-fixed tissue mitotic cells appeared as bright spots in immunofluorescence using an antibody specific for the phosphorylation site Thr421/Ser424. They were easily spotted in overviews with the objective 4× and 10×. Immunofluorescence was weak during the interphase. During the prophase it increased in both the nucleus and the cytoplasm and it remained bright during the subsequent phases of mitosis. All mitotic cells which were found in tubules and in the interstitium of the kidney using a chromatin stain displayed the bright immunofluorescence for phospho-S6 kinase. The same phenomenon was observed in rat liver and in mouse kidney as well as in a human cell line. Provided a rapid fixation, mitotic cells could be identified with the immunoperoxidase technique in paraffin sections of immersion-fixed tissue. This is the first report of phosphorylation of S6 kinase during mitosis in vivo. Thus, immunohistochemistry with anti-phospho-S6 kinase (Thr421/Ser424) appears to provide a convenient way to detect mitotic cells at low magnificatio

The baseline immunological and hygienic status of pigs impact disease severity of African swine fever.

African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs, associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance

Chronic Norovirus Infection after Kidney Transplantation: Molecular Evidence for Immune-Driven Viral Evolution

Background. Norovirus infection is the most common cause of acute self-limiting gastroenteritis. Only 3 cases of chronic norovirus infection in adult solid organ transplant recipients have been reported thus far. Methods. This case series describes 9 consecutive kidney allograft recipients with chronic norovirus infection with persistent virus shedding and intermittent diarrhea for a duration of 97-898 days. The follow-up includes clinical course, type of immunosuppression, and polymerase chain reaction for norovirus. Detailed molecular analyses of virus isolates from stool specimens over time were performed. Results. The intensity of immunosuppression correlated with the diarrheal symptoms but not with viral shedding. Molecular analysis of virus strains from each patient revealed infection with different variants of GII.4 strains in 7 of 9 patients. Another 2 patients were infected with either the GII.7 or GII.17 strain. No molecular evidence for nosocomial transmission in our outpatient clinic was found. Capsid sequence alignments from follow-up specimens of 4 patients showed accumulation of mutations over time, resulting in amino acid changes predominantly in the P2 and P1-2 region. Up to 25 amino acids mutations were accumulated over a 683-day period in the patient with an 898-day shedding history. Conclusion. Norovirus infection may persist in adult renal allograft recipients with or without clinical symptoms. No evidence for nosocomial transmission in adult renal allograft recipients was found in our study. Molecular analysis suggests continuous viral evolution in immunocompromised patients who are unable to clear this infectio