Efficient Computation of Multiple Density-Based Clustering Hierarchies

HDBSCAN*, a state-of-the-art density-based hierarchical clustering method, produces a hierarchical organization of clusters in a dataset w.r.t. a parameter mpts. While the performance of HDBSCAN* is robust w.r.t. mpts in the sense that a small change in mpts typically leads to only a small or no change in the clustering structure, choosing a "good" mpts value can be challenging: depending on the data distribution, a high or low value for mpts may be more appropriate, and certain data clusters may reveal themselves at different values of mpts. To explore results for a range of mpts values, however, one has to run HDBSCAN* for each value in the range independently, which is computationally inefficient. In this paper, we propose an efficient approach to compute all HDBSCAN* hierarchies for a range of mpts values by replacing the graph used by HDBSCAN* with a much smaller graph that is guaranteed to contain the required information. An extensive experimental evaluation shows that with our approach one can obtain over one hundred hierarchies for the computational cost equivalent to running HDBSCAN* about 2 times.Comment: A short version of this paper appears at IEEE ICDM 2017. Corrected typos. Revised abstrac

Pre-orchiectomy tumor marker levels should not be used for International Germ Cell Consensus Classification (IGCCCG) risk group assignment

PURPOSE To investigate whether the use of pre-orchiectomy instead of pre-chemotherapy tumor marker (TM) levels has an impact on the International Germ Cell Consensus Classification (IGCCCG) risk group assignment in patients with metastatic germ cell tumors (GCT). METHODS Demographic and clinical information of all patients treated for primary metastatic testicular non-seminomatous GCT in our tertiary care academic center were extracted from medical charts. IGCCCG risk group assignment was correctly performed with pre-chemotherapy marker levels and additionally with pre-orchiectomy marker levels. Agreement between pre-chemotherapy and pre-orchiectomy risk group assignments was assessed using Cohen's kappa. RESULTS Our cohort consisted of 83 patients. The use of pre-orchiectomy TMs resulted in an IGCCCG risk group upstaging in 12 patients (16%, 8 patients from good to intermediate risk and 4 patients from intermediate to poor risk) and a downstaging in 1 patient (1.2%, from intermediate- to good-risk). The agreement between pre-orchiectomy and pre-chemotherapy IGCCCG risk groups resulted in a Cohen's kappa of 0.888 (p < 0.001). CONCLUSIONS Using pre-orchiectomy TMs can result in incorrect IGCCCG risk group assignment, which in turn can impact on the clinical management and follow-up of patients with metastatic GCT. Thus, adherence to the IGCCCG standard using pre-chemotherapy TMs levels is recommended

(Dis) integrated valuation - Assessing the information gaps in ecosystem service appraisals for governance support

The operational challenges of integrated ecosystem service (ES) appraisals are determined by study purpose, system complexity and uncertainty, decision-makers' requirements for reliability and accuracy of methods, and approaches to stakeholder-science interaction in different decision contexts. To explore these factors we defined an information gap hypothesis, based on a theory of cumulative uncertainty in ES appraisals. When decision context requirements for accuracy and reliability increase, and the expected uncertainty of the ES appraisal methods also increases, the likelihood of methods being used is expected to drop, creating a potential information gap in governance. In order to test this information gap hypothesis, we evaluate 26 case studies and 80 ecosystem services appraisals in a large integrated EU research project. We find some support for a decreasing likelihood of ES appraisal methods coinciding with increasing accuracy and reliability requirements of the decision-support context, and with increasing uncertainty. We do not find that information costs are the explanation for this information gap, but rather that the research project interacted mostly with stakeholders outside the most decision-relevant contexts. The paper discusses how alternative definitions of integrated valuation can lead to different interpretations of decision-support information, and different governance approaches to dealing with uncertainty. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Integrating methods for ecosystem service assessment: Experiences from real world situations

The Ecosystem Services (ES) concept highlights the varied contributions the environment provides to humans and there are a wide range of methods/tools available to assess ES. However, in real-world decision contexts a single tool is rarely sufficient and methods must be combined to meet practitioner needs. Here, results from the OpenNESS project are presented to illustrate the methods selected to meet the needs of 24 real-world case studies and better understand why and how methods are combined to meet practical needs. Results showed that within the cases methods were combined to: i) address a range of ES; ii) assess both supply and demand of ES; iii) assess a range of value types; iv) reach different stake-holder groups v) cover weaknesses in other methods used and vi) to meet specific decision context needs. Methods were linked in a variety of ways: i) as input-output chains of methods; ii) through learning; iii) through method development and iv) through comparison/triangulation of results. The paper synthesises these case study-based experiences to provide insight to others working in practical contexts as to where, and in what contexts, different methods can be combined and how this can add value to case study analyses. (C) 2017 Published by Elsevier B.V.Peer reviewe

Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis, Perturbation of Which Leads to Masculinization Disorders in Rodents

Reproductive disorders that are common/increasing in prevalence in human males may arise because of deficient androgen production/action during a fetal ‘masculinization programming window’. We identify a potentially important role for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) in Leydig cell (LC) steroidogenesis that may partly explain this. In rats, fetal LC size and intratesticular testosterone (ITT) increased ∼3-fold between e15.5-e21.5 which associated with a progressive decrease in the percentage of LC expressing COUP-TFII. Exposure of fetuses to dibutyl phthalate (DBP), which induces masculinization disorders, dose-dependently prevented the age-related decrease in LC COUP-TFII expression and the normal increases in LC size and ITT. We show that nuclear COUP-TFII expression in fetal rat LC relates inversely to LC expression of steroidogenic factor-1 (SF-1)-dependent genes (StAR, Cyp11a1, Cyp17a1) with overlapping binding sites for SF-1 and COUP-TFII in their promoter regions, but does not affect an SF-1 dependent LC gene (3β-HSD) without overlapping sites. We also show that once COUP-TFII expression in LC has switched off, it is re-induced by DBP exposure, coincident with suppression of ITT. Furthermore, other treatments that reduce fetal ITT in rats (dexamethasone, diethylstilbestrol (DES)) also maintain/induce LC nuclear expression of COUP-TFII. In contrast to rats, in mice DBP neither causes persistence of fetal LC COUP-TFII nor reduces ITT, whereas DES-exposure of mice maintains COUP-TFII expression in fetal LC and decreases ITT, as in rats. These findings suggest that lifting of repression by COUP-TFII may be an important mechanism that promotes increased testosterone production by fetal LC to drive masculinization. As we also show an age-related decline in expression of COUP-TFII in human fetal LC, this mechanism may also be functional in humans, and its susceptibility to disruption by environmental chemicals, stress and pregnancy hormones could explain the origin of some human male reproductive disorders

Integrated assessment and valuation of ecosystem services - Guidelines and experiences

EU FP7 OpenNESS project deliverable D33 & D4

Wissenschaftliche Begründung der STIKO zur Implementierung der COVID-19-Impfung in die allgemeinen Empfehlungen der STIKO 2023

Die COVID-19-Impfempfehlungen der STIKO ha¬ben seit Beginn der Impfkampagne im Winter 2020/2021 das vordringliche Ziel, schwere Verläufe und Langzeit¬folgen von COVID-19 zu verhindern sowie Beschäf¬tigte in der medizinischen und pflegenden Versor¬gung vor SARS-CoV-2-Infektionen zu schützen. Die STIKO hat ihre COVID-19-Impfempfehlung seit der Erstpublikation im Dezember 2020 unter der Berücksichtigung neuer Daten und wei¬teren Impfstoffzulassungen fortlaufend angepasst. Beim Übergang von der pandemischen in die ende¬mische Phase des Infektionsgeschehens hat sich die STIKO mit der Überführung der bisherigen Emp¬fehlungen in eine längerfristige COVID-19-Impfempfehlung befasst. Im Epidemiologischen Bulletin 21/2023 wird die dazugehörige wissenschaftliche Begründung der aktualisierten Empfehlung und der Integration in den Impfkalender veröffentlicht. Die neue Empfehlung ersetzt die 25. Aktualisierung der COVID-19-Impfempfehlung von Februar 2023, die nicht mehr länger gültig ist

Wissenschaftliche Begründung der STIKO zur Implementierung der COVID-19-Impfung in die allgemeinen Empfehlungen der STIKO 2023

Die COVID-19-Impfempfehlungen der STIKO ha¬ben seit Beginn der Impfkampagne im Winter 2020/2021 das vordringliche Ziel, schwere Verläufe und Langzeit¬folgen von COVID-19 zu verhindern sowie Beschäf¬tigte in der medizinischen und pflegenden Versor¬gung vor SARS-CoV-2-Infektionen zu schützen. Die STIKO hat ihre COVID-19-Impfempfehlung seit der Erstpublikation im Dezember 2020 unter der Berücksichtigung neuer Daten und wei¬teren Impfstoffzulassungen fortlaufend angepasst. Beim Übergang von der pandemischen in die ende¬mische Phase des Infektionsgeschehens hat sich die STIKO mit der Überführung der bisherigen Emp¬fehlungen in eine längerfristige COVID-19-Impfempfehlung befasst. Im Epidemiologischen Bulletin 21/2023 wird die dazugehörige wissenschaftliche Begründung der aktualisierten Empfehlung und der Integration in den Impfkalender veröffentlicht. Die neue Empfehlung ersetzt die 25. Aktualisierung der COVID-19-Impfempfehlung von Februar 2023, die nicht mehr länger gültig ist

Wissenschaftliche Begründung der STIKO zur Implementierung der COVID-19-Impfung in die allgemeinen Empfehlungen der STIKO 2023

Die COVID-19-Impfempfehlungen der STIKO ha¬ben seit Beginn der Impfkampagne im Winter 2020/2021 das vordringliche Ziel, schwere Verläufe und Langzeit¬folgen von COVID-19 zu verhindern sowie Beschäf¬tigte in der medizinischen und pflegenden Versor¬gung vor SARS-CoV-2-Infektionen zu schützen. Die STIKO hat ihre COVID-19-Impfempfehlung seit der Erstpublikation im Dezember 2020 unter der Berücksichtigung neuer Daten und wei¬teren Impfstoffzulassungen fortlaufend angepasst. Beim Übergang von der pandemischen in die ende¬mische Phase des Infektionsgeschehens hat sich die STIKO mit der Überführung der bisherigen Emp¬fehlungen in eine längerfristige COVID-19-Impfempfehlung befasst. Im Epidemiologischen Bulletin 21/2023 wird die dazugehörige wissenschaftliche Begründung der aktualisierten Empfehlung und der Integration in den Impfkalender veröffentlicht. Die neue Empfehlung ersetzt die 25. Aktualisierung der COVID-19-Impfempfehlung von Februar 2023, die nicht mehr länger gültig ist