Classification of tools and methods for knowledge management in product development

"Der Fortschritt lebt vom Austausch des Wissens" (Progress is based on the exchange of knowledge - Albert Einstein), is only one of many famous sayings that underline the importance of knowledge. [Vajna et. al. 2001] quote a statement from 1907 saying that besides dedicated employees the application of knowledge had already been one of the most decisive factors of success for companies that time. This is more applied to our, by globalization characterised, time. A neglect of existing potentials of the employees\u27 knowledge has negative impacts on product development [Krause et. al. 2007]. That is why the missing accessibility of personal knowledge to the company and its employees leads to wasting in the company in the form of redundant developments or dissimilar decisions [Probst et. al. 2006]. Only a structured and systematic management of knowledge resources enables a company to benefit from yet unused personal knowledge [Krause et. al. 2007] and, thus, to positively influence the main targets cost, time and quality [Klabunde 2003]. Recently, a huge number of innovative knowledge management methods and tools have been developed, but only few of them have been applied. Problems that hinder the application of those methods and tools have been discussed by [Klabunde 2003]. Among these is also the limited usage of the tools due to missing knowledge about the usage. The aim of this paper is to combine knowledge management tools and methods with product development. The method to do this is to consider the knowledge management blocks according to Probst [Probst et.al. 2006], deriving from the area of business administration, in the context of the product development process according to VDI 2221 [VDI 1993]. Based on this consideration, the goal of this contribution is to identify and propose existing solutions for knowledge management in the different phases of product development

Shape-specific characterization of colorectal adenoma growth and transition to cancer with stochastic cell-based models

Colorectal adenoma are precursor lesions on the pathway to cancer. Their removal in screening colonoscopies has markedly reduced rates of cancer incidence and death. Generic models of adenoma growth and transition to cancer can guide the implementation of screening strategies. But adenoma shape has rarely featured as a relevant risk factor. Against this backdrop we aim to demonstrate that shape influences growth dynamics and cancer risk. Stochastic cell-based models are applied to a data set of 197,347 Bavarian outpatients who had colonoscopies from 2006-2009, 50,649 patients were reported with adenoma and 296 patients had cancer. For multi-stage clonal expansion (MSCE) models with up to three initiating stages parameters were estimated by fits to data sets of all shapes combined, and of sessile (70% of all adenoma), peduncular (17%) and flat (13%) adenoma separately for both sexes. Pertinent features of adenoma growth present themselves in contrast to previous assumptions. Stem cells with initial molecular changes residing in early adenoma predominantly multiply within two-dimensional structures such as crypts. For these cells mutation and division rates decrease with age. The absolute number of initiated cells in an adenoma of size 1 cm is small around 10(3), related to all bulk cells they constitute a share of about 10(−5). The notion of very few proliferating stem cells with age-decreasing division rates is supported by cell marker experiments. The probability for adenoma transiting to cancer increases with squared linear size and shows a shape dependence. Compared to peduncular and flat adenoma, it is twice as high for sessile adenoma of the same size. We present a simple mathematical expression for the hazard ratio of interval cancers which provides a mechanistic understanding of this important quality indicator. We conclude that adenoma shape deserves closer consideration in screening strategies and as risk factor for transition to cancer

Exposure-lag-response associations between lung cancer mortality and radon exposure in German uranium miners.

Exposure-lag-response associations shed light on the duration of pathogenesis for radiation-induced diseases. To investigate such relations for lung cancer mortality in the German uranium miners of the Wismut company, we apply distributed lag non-linear models (DLNMs) which offer a flexible description of the lagged risk response to protracted radon exposure. Exposure-lag functions are implemented with B-Splines in Cox models of proportional hazards. The DLNM approach yielded good agreement of exposure-lag-response surfaces for the German cohort and for the previously studied cohort of American Colorado miners. For both cohorts, a minimum lag of about 2 year for the onset of risk after first exposure explained the data well, but possibly with large uncertainty. Risk estimates from DLNMs were directly compared with estimates from both standard radio-epidemiological models and biologically based mechanistic models. For age > 45 year, all models predict decreasing estimates of the Excess Relative Risk (ERR). However, at younger age, marked differences appear as DLNMs exhibit ERR peaks, which are not detected by the other models. After comparing exposure-responses for biological processes in mechanistic risk models with exposure-responses for hazard ratios in DLNMs, we propose a typical period of 15 year for radon-related lung carcinogenesis. The period covers the onset of radiation-induced inflammation of lung tissue until cancer death. The DLNM framework provides a view on age-risk patterns supplemental to the standard radio-epidemiological approach and to biologically based modeling

Simulating the dynamics of atherosclerosis to the incidence of myocardial infarction, applied to the KORA population

Analyzing epidemiological data with simplified mathematical models of disease development provides a link between the time-course of incidence and the underlying biological processes. Here we point out that considerable modeling flexibility is gained if the model is solved by simulation only. To this aim, a model of atherosclerosis is proposed: a Markov Chain with continuous state space which represents the coronary artery intimal surface area involved with atherosclerotic lesions of increasing severity. Myocardial infarction rates are assumed to be proportional to the area of most severe lesions. The model can be fitted simultaneously to infarction incidence rates observed in the KORA registry, and to the age-dependent prevalence and extent of atherosclerotic lesions in the PDAY study. Moreover, the simulation approach allows for non-linear transition rates, and to consider at the same time randomness and inter-individual heterogeneity. Interestingly, the fit revealed significant age dependence of parameters in females around the age of menopause, qualitatively reproducing the known vascular effects of female sex hormones. For males, the incidence curve flattens for higher ages. According to the model, frailty explains this flattening only partially, and saturation of the disease process plays also an important role. This study shows the feasibility of simulating subclinical and epidemiological data with the same mathematical model. The approach is very general and may be extended to investigate the effects of risk factors or interventions. Moreover, it offers an interface to integrate quantitative individual health data as assessed, for example, by imaging

Longitudinal atherosclerotic changes after radio(chemo)therapy of hypopharyngeal carcinoma

Background Radiotherapy treatment of head and neck cancer affects local arteries and increases the risk of stroke. This study aimed at a closer characterization of this damage and its development in time with a longitudinal study set up. Methods Male patients treated between 2011 and 2016 for hypopharyngeal carcinoma were identified from the in-house clinical data base. They were included into the study if besides the planning CT at least one additional CT image was available from follow-up (13 patients) or at least two MRI scans (16 patients of which 2 were already included). All patients received radiotherapy, and chemotherapy was administered to 16 patients. The time from the beginning of radiotherapy to the last available image ranged from 2 months to 4.5 years. For six segments of the carotid arteries, the number and volume of atherosclerotic plaques were determined from the CT scans, and the intima media thickness from the MRI scans. Information on comorbid cardiovascular disease, hypertension and diabetes mellitus was retrieved from medical records. Results Total plaque volume rose from 0.25 cm3 before to 0.33 cm3 after therapy but this was not significant (p = 0.26). The mean number of plaques increased from 5.7 to 8.1 (p = 0.002), and the intima media thickened from 1.17 mm to 1.35 mm (p = 0.002). However, the mean intima media thickness practically did not change in patients with comorbid diabetes mellitus (p-value for homogeneity: 0.03). For patients without diabetes mellitus, dynamics of both plaque number and intima media thickness, was consistent with an increase until about one year after therapy and no further progression thereafter. Conclusion Our study confirmed the thickening of artery walls and the increase in the number of plaques. Results imply that definitive radiation damage to the artery walls can be determined not earlier than about one year after radiotherapy and there is no substantial deterioration thereafter. Reasons for the absence of an observable intima media thickening in patients with diabetes are unclear

Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria

Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity

Psychographische Verortung von Menschen mit Diabetes: Auswirkungen auf die Produktgestaltung und Kommunikation

Für den Erfolg eines Produktes oder einer Dienstleistung ist die umfassende Kenntnis der Bedürfnisse, Wahrnehmungs- und Entscheidungsfilter von Zielgruppen entscheidend. Nur eine zielgerichtete, zur Zielgruppe passende Produktentwicklung und -vermarktung kann Auf Dauer erfolgreich sein. Da soziodemographische Zielgruppendefinitionen heute alleine nicht valide genug sind, um Zielgruppen umfassend zu verstehen, werden im Marketing zu-nehmend psychographische Verortungen von Zielgruppen verwendet. Auch bei chronisch Kranken reichen rein soziodemographische und medizinische Kriterien nicht aus, um Produkte und Dienstleistungen passend zu gestalten. Psychographische Erkenntnisse können die klassischen Kriterien sinnvoll ergänzen. Am Beispiel von Menschen mit Diabetes wird in einer internationalen empirischen Studie gezeigt, dass sich Menschen mit Diabetes mit Hilfe eines neuropsychologisch fundierten, visuellen Testverfahrens (dem u.a. an der NORD-AKADEMIE entwickelten Visual Questionnaire, ViQ) eindeutig psychographisch verorten lassen. Die Implikationen und Anwendungsmöglichkeiten dieser psychographischen Erkenntnisse für die Produktentwicklung, Kommunikation, Vertrieb und Marketing bei Krankenkassen, medizinischem Personal und der Pharmabranche werden aufgezeigt und kritisch diskutiert. --

The BrainScaleS-2 Neuromorphic Platform — A Report on the Integration and Operation of an Open Science Hardware Platform within EBRAINS

This report presents the challenges encountered and the solutions created for the operation of the BrainScaleS neuromorphic platform, and the overall progress leading to this state at the end of the Human Brain Project (HBP)

Cepheids in M31: The PAndromeda Cepheid Sample

We present the largest Cepheid sample in M31 based on the complete Pan-STARRS1 survey of Andromeda (PAndromeda) in the r P1, i P1, and g P1 bands. We find 2686 Cepheids with 1662 fundamental-mode Cepheids, 307 first-overtone Cepheids, 278 type II Cepheids, and 439 Cepheids with undetermined Cepheid type. Using the method developed by Kodric et al., we identify Cepheids by using a three-dimensional parameter space of Fourier parameters of the Cepheid light curves combined with a color cut and other selection criteria. This is an unbiased approach to identify Cepheids and results in a homogeneous Cepheid sample. The period–luminosity relations obtained for our sample have smaller dispersions than in our previous work. We find a broken slope that we previously observed with HST data in Kodric et al., albeit with a lower significance

Treatment of Older Patients With Mantle Cell Lymphoma (MCL):Long-Term Follow-Up of the Randomized European MCL Elderly Trial

PURPOSE: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS: After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION: The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe