Spatio-temporal heterogeneity of riparian soil morphology in a restored floodplain

Floodplains have been intensively altered in industrialized countries, but are now increasingly being restored. It is therefore important to assess the effect of these restoration projects on the aquatic and terrestrial components of ecosystems. However, despite being functionally crucial components of terrestrial ecosystems, soils are generally overlooked in floodplain restoration assessments. We studied the spatio-temporal heterogeneity of soil morphology in a restored (riverbed widening) river reach along the River Thur (Switzerland) using three criteria (soil diversity, dynamism and typicality) and their associated indicators. We hypothesized that these criteria would correctly discriminate the post-restoration changes in soil morphology, and that these changes correspond to patterns of vascular plant diversity. <br><br> Soil diversity and dynamism increased 5 yr after the restoration, but some typical soils of braided rivers were still missing. Soil typicality and dynamism were correlated to vegetation changes. These results suggest a limited success of the project, in agreement with evaluations carried out at the same site using other, more resource-demanding, methods (e.g., soil fauna, fish diversity, ecosystem functioning). <br><br> Soil morphology provides structural and functional information on floodplain ecosystems. The spatio-temporal heterogeneity of soil morphology represents a cost-efficient ecological indicator that could easily be integrated into rapid assessment protocols of floodplain and river restoration projects. <br><br> The follow-up assessment after several major floods (≥ HQ20) should take place to allow for testing the longer-term validity of our conclusion for the River Thur site. More generally, it would be useful to apply the soil morphology indicator approach in different settings to test its broader applicability

A Performance-Based Scenario Methodology to Assess Collaborative Networks Business Model Dynamicity

[EN] In today's business marketplace many enterprises collaborate forming a collaborative network (CN) in order to achieve competitive and sustainable advantages. In this context, CNs should have not only well-defined business models but also mechanisms and tools that help them out to assess such business models as well as other CN operations at their early stages. Due to shorter life-cycles and to the current fierce competition such an evaluation should be made as quickly as possible and analyzing real data rather than based on opinions and subjective judgments. This paper presents the application of a methodology that allows such an assessment as well as the generation of business scenarios based on the performance of the CN. Then, it first defines the appropriate CN key performance indicators (KPIs), gathering data for a certain time-period; then, it applies multivariate techniques to this data, identifying relationships between the KPIs, and being able to build the timely evolution of the CN based on this data; next, it is able to design a business scenario based on the timely evolution that the CN should have according to its business models and operations results achieved so far. With all this additional information decision-makers could decide whether the CN's business models succeeded or not so far and what actions to take in order to achieve the future desirable scenario.This work has been developed within the research project called “Design of business scenarios to improve the efficiency and management of industrial supply chain” (reference GV/2013/045).Rodríguez Rodríguez, R.; Alfaro Saiz, JJ.; Verdecho Sáez, MJ. (2015). A Performance-Based Scenario Methodology to Assess Collaborative Networks Business Model Dynamicity. IFIP Advances in Information and Communication Technology. 463:511-517. https://doi.org/10.1007/978-3-319-24141-8_47S511517463Achtenhagen, L., Melin, L., Naldi, L.: Dynamics of business models – strategizing, critical capabilities and activities for sustained value creation. Long Range Plann. 46, 427–442 (2013)Chesbrough, H.: Business model innovation: opportunities and barriers. Long Range Plann. 43, 354–363 (2010)Chermack, T.J.: Studying scenario planning: theory, research, suggestions, and hypotheses. Technol. Forecast. Soc. Change 72, 59–73 (2005)Harries, C.: Correspondence to what? Coherence to what? What is good scenario-based decision making? Technol. Forecast. Soc. Change 70, 797–817 (2003)Gunasekaran, A., Patel, C., Tirtiroglu, E.: Performance measures and metrics in a supply chain environment. Int. J. Oper. Prod. Manage. 21, 71–87 (2001)Bullinger, H.J., Kühner, M., Hoof, A.V.: Analysing supply chain performance using a balanced measurement method. Int. J. Prod. Res. 40, 3533–3543 (2002)Folan, P., Browne, J.: Development of an extended enterprise performance measurement system. Prod. Plann. Control 16, 531–544 (2005)Fink, A., Marr, B., Siebe, A., Khule, J.-P.: The future scorecard: combining external and internal scenarios to create strategic foresight. Manage. Decis. 43, 360–381 (2005)Othman, R.: Enhancing the effectiveness of the balanced scorecard with scenario planning. Int. J. Prod. Perform. Manage. 57, 259–266 (2008)Rodriguez-Rodriguez, R., Saiz, J.J.A., Bas, A.O., Carot, J.M., Jabaloyes, J.M.: Building internal business scenarios based on real data from a performance measurement system. Technol. Forecast. Soc. Change 77, 50–62 (2010

A measurement model for general noise reaction in response to aircraft noise

In this paper a measurement model for general noise reaction (GNR) in response to aircraft noise is developed to assess the performance of aircraft noise annoyance and a direct measure of general reaction as indicators of this concept. For this purpose GNR is conceptualized as a superordinate latent construct underlying particular manifestations. This conceptualization is empirically tested through estimation of a second-order factor model. Data from a community survey at Frankfurt Airport are used for this purpose (N = 2206). The data fit the hypothesized factor structure well and support the conceptualization of GNR as a superordinate construct. It is concluded that noise annoyance and a direct measure of general reaction to noise capture a large part of the negative feelings and emotions in response to aircraft noise but are unable to capture all relevant variance. The paper concludes with recommendations for the valid measurement of community reaction and several directions for further research.Infrastructures, Systems and ServicesTechnology, Policy and Managemen

The European DISABKIDS project: development of seven condition-specific modules to measure health related quality of life in children and adolescents

BACKGROUND: The European DISABKIDS project aims to enhance the Health Related Quality of Life (HRQoL) of children and adolescents with chronic medical conditions and their families. We describe the development of the seven cross-nationally tested condition-specific modules of the European DISABKIDS HRQoL instrument in a population of children and adolescents. The condition-specific modules are intended for use in conjunction with the DISABKIDS chronic generic module. METHODS: Focus groups were used to construct the pilot version of the DISABKIDS condition-specific HRQoL modules for asthma, juvenile idiopathic arthritis, atopic dermatitis, cerebral palsy, cystic fibrosis, diabetes and epilepsy. Analyses were conducted on pilot test data in order to construct field test versions of the modules. A series of factor analyses were run, first, to determine potential structures for each condition-specific module, and, secondly, to select a reduced number of items from the pilot test to be included in the field test. Post-field test analyses were conducted to retest the domain structure for the final DISABKIDS condition-specific modules. RESULTS: The DISABKIDS condition-specific modules were tested in a pilot study of 360 respondents, and subsequently in a field test of 1152 respondents in 7 European countries. The final condition-specific modules consist of an 'Impact' domain and an additional domain (e.g. worry, stigma, treatment) with between 10 to 12 items in total. The Cronbach's alpha of the final domains was found to vary from 0.71 to 0.90. CONCLUSION: The condition-specific modules of the DISABKIDS instrument were developed through a step-by-step process including cognitive interview, clinical expertise, factor analysis, correlations and internal consistency. A cross-national pilot and field test were necessary to collect these data. In general, the internal consistency of the domains was satisfactory to high. In future, the DISABKIDS instrument may serve as a useful tool with which to assess HRQoL in children and adolescents with a chronic condition. The condition-specific modules can be used in conjunction with the DISABKIDS chronic generic module

Survival differences and associated molecular signatures of DNMT3A-mutant acute myeloid leukemia patients

Acute myeloid leukemia (AML) is a very heterogeneous and highly malignant blood cancer. Mutations of the DNA methyltransferase DNMT3A are among the most frequent recurrent genetic lesions in AML. The majority of DNMT3A-mutant AML patients shows fast relapse and poor survival, but also patients with long survival or long-term remission have been reported. Underlying molecular signatures and mechanisms that contribute to these survival differences are only poorly understood and have not been studied in detail so far. We applied hierarchical clustering to somatic gene mutation profiles of 51 DNMT3A-mutant patients from The Cancer Genome Atlas (TCGA) AML cohort revealing two robust patient subgroups with profound differences in survival. We further determined molecular signatures that distinguish both subgroups. Our results suggest that FLT3 and/or NPM1 mutations contribute to survival differences of DNMT3A-mutant patients. We observed an upregulation of genes of the p53, VEGF and DNA replication pathway and a downregulation of genes of the PI3K-Akt pathway in short- compared to long-lived patients. We identified that the majority of measured miRNAs was downregulated in the short-lived group and we found differentially expressed microRNAs between both subgroups that have not been reported for AML so far (miR-153-2, miR-3065, miR-95, miR-6718) suggesting that miRNAs could be important for prognosis. In addition, we learned gene regulatory networks to predict potential major regulators and found several genes and miRNAs with known roles in AML pathogenesis, but also interesting novel candidates involved in the regulation of hematopoiesis, cell cycle, cell differentiation, and immunity that may contribute to the observed survival differences of both subgroups and could therefore be important for prognosis. Moreover, the characteristic gene mutation and expression signatures that distinguished short- from long-lived patients were also predictive for independent DNMT3A-mutant AML patients from other cohorts and could also contribute to further improve the European LeukemiaNet (ELN) prognostic scoring system. Our study represents the first in-depth computational approach to identify molecular factors associated with survival differences of DNMT3A-mutant AML patients and could trigger additional studies to develop robust molecular markers for a better stratification of AML patients with DNMT3A mutations

Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol

Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978

Immune phenotypes and checkpoint molecule expression of clonally expanded lymph node-infiltrating T cells in classical Hodgkin lymphoma

Lymph node-infiltrating T cells have been of particular interest in classical Hodgkin lymphoma (cHL). High rates of complete therapeutic responses to antibody-mediated immune checkpoint blockade, even in relapsed/refractory patients, suggest the existence of a T cell-dominated, antigen-experienced, functionally inhibited and lymphoma-directed immune microenvironment. We asked whether clonally expanded T cells (1) were detectable in cHL lymph nodes, (2) showed characteristic immune phenotypes, and (3) were inhibited by immune checkpoint molecule expression. We applied high-dimensional FACS index sorting and single cell T cell receptor αβ sequencing to lymph node-infiltrating T cells from 10 treatment-naïve patients. T cells were predominantly CD4(+) and showed memory differentiation. Expression of classical immune checkpoint molecules (CTLA-4, PD-1, TIM-3) was generally low (< 12.0% of T cells) and not different between CD4(+) and CD8(+) T cells. Degrees of clonal T cell expansion varied between patients (range: 1-18 expanded clones per patient) and was almost exclusively restricted to CD8(+) T cells. Clonally expanded T cells showed non-naïve phenotypes and low checkpoint molecule expression similar to non-expanded T cells. Our data suggest that the therapeutic effects of immune checkpoint blockade require mechanisms in addition to dis-inhibition of pre-existing lymphoma-directed T cell responses. Future studies on immune checkpoint blockade-associated effects will identify molecular T cell targets, address dynamic aspects of cell compositions over time, and extend their focus beyond lymph node-infiltrating T cells

Widely applicable, extended flow cytometric stem cell enumeration panel for quality control of advanced cellular products

The most widely used quality control assay for CD34 + hematopoietic stem cell product characterization is the protocol established by the International Society of Hematotherapy and Graft Engineering (ISHAGE). While this protocol is still the gold standard for stem cell enumeration and viability assessment, it does not include T cell enumeration, which is nowadays mandatory for assaying standard allogeneic grafts and various advanced therapy medicinal products (ATMPs). In accordance, we have developed and extensively validated a new approach for a more comprehensive characterization of hematopoietic cellular products using a pre-formulated dried antibody format panel. In addition to the counting beads, the typical markers CD45 fluorescein isothiocyanate (FITC) and CD34 phycoerythrin (PE), as well as the viability dye 7-amino actinomycin D (7-AAD), our novel pre-formulated panel also contains CD3 Pacific Blue (PB) and CD19 allophycocyanin (APC) in the same tube, thereby allowing a combined calculation of leucocytes, stem cells, T and B cells. Showing high linearity, sensitivity and accuracy, our approach is easy to implement and enables a more in-depth characterization of the cellular product under release testing conditions. In addition, the dried pre-formulated antibody approach increases assay reliability compared to the standard antibody panel

Synthetic Lethal Interaction between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells

An alternative to therapeutic targeting of oncogenes is to perform “synthetic lethality” screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of mutant KRAS-driven cancers and demonstrate the potential of RNAi screens for discovering functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers with “undruggable” genetic alterations.National Institutes of Health (U.S.) (grant R33 CA128625)National Institutes of Health (U.S.) (grant NIH U54 CA112962)National Institutes of Health (U.S.) (grant P01 CA095616)National Institutes of Health (U.S.) (grant P01 CA66996)Starr Cancer ConsortiumDoris Duke Charitable FoundationMPN Research FoundationDeutsche Forschungsgemeinschaft (grant SCHO 1215/1-1)Deutsche Forschungsgemeinschaft (grant FR 2113/1-1)Brain Science FoundationLeukemia & Lymphoma Society of Americ