Information Management in Product Development Workflows – A Novel Approach on the basis of Pseudonymization of Product Information

AbstractInformation stored in the documentation of a product constitutes in many aspects the intellectual property (IP) of an enterprise. This valuable knowledge, built over years of extensive research and development deserves special attention and protection. Especially the context of distributed product development activities and increased collaborations with external partners puts companies at a growing risk that unauthorized individuals obtain access to this prized capital. In this paper, we present a novel concept for managing and sharing sensitive information in product development processes. Product information is separated and subsequently pseudonymized into independent blocks of data fragments which can be reassembled to specific information levels depending on the requirements of the organization. Thus, a user can be given access to that level of information specifically required to complete the task. The product information itself is only available as unordered data fragments and no longer interpretable even in case of data theft. By doing so, a comprehensive protection against internal and external abuse of sensitive product information can be realized which can easily be combined with existing concepts in the field of information protection

In-vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [¹¹C]<i>(R)</i>-PK11195 positron emission tomography study

Abstract Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO) has been used to investigate whether microglial activation, an indication of neuroinflammation, is evident in the brain of adults with schizophrenia. Interpretation of these studies is confounded by potential modulatory effects of antipsychotic medication on microglial activity. In the first such study in antipsychotic-free schizophrenia, we have used [11C](R)-PK11195 PET to compare TSPO availability in a predominantly antipsychotic-naive group of moderate-to-severely symptomatic unmedicated patients (n=8), similarly symptomatic medicated patients with schizophrenia taking risperidone or paliperidone by regular intramuscular injection (n=8), and healthy comparison subjects (n=16). We found no evidence for increased TSPO availability in antipsychotic-free patients compared with healthy controls (mean difference 4%, P=0.981). However, TSPO availability was significantly elevated in medicated patients (mean increase 88%, P=0.032) across prefrontal (dorsolateral, ventrolateral, orbital), anterior cingulate and parietal cortical regions. In the patients, TSPO availability was also strongly correlated with negative symptoms measured using the Positive and Negative Syndrome Scale across all the brain regions investigated (r=0.651-0.741). We conclude that the pathophysiology of schizophrenia is not associated with microglial activation in the 2-6 year period following diagnosis. The elevation in the medicated patients may be a direct effect of the antipsychotic, although this study cannot exclude treatment resistance and/or longer illness duration as potential explanations. It also remains to be determined whether it is present only in a subset of patients, represents a pro- or anti-inflammatory state, its association with primary negative symptoms, and whether there are significant differences between antipsychotics

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Microglial activation, white matter tract damage and disability in multiple sclerosis

Abstract Objective: To investigate the relationship of in vivo microglial activation to clinical and MRI parameters in MS. Methods: Patients with secondary progressive MS (n = 10) or relapsing-remitting MS (n = 10) and age-matched healthy controls (n = 17) were studied. Microglial activation was measured using PET and radioligand [11C](R)-PK11195. Clinical assessment and structural and quantitative MRI including diffusion tensor imaging (DTI) were performed for comparison. Results: [11C](R)-PK11195 binding was significantly higher in the normal-appearing white matter (NAWM) of patients with secondary progressive vs relapsing MS and healthy controls, in the thalami of patients with secondary progressive MS vs controls, and in the perilesional area among the progressive compared with relapsing patients. Higher binding in the NAWM was associated with higher clinical disability and reduced white matter (WM) structural integrity, as shown by lower fractional anisotropy, higher mean diffusivity, and increased WM lesion load. Increasing age contributed to higher microglial activation in the NAWM among patients with MS but not in healthy controls. Conclusions: PET can be used to quantitate microglial activation, which associates with MS progression. This study demonstrates that increased microglial activity in the NAWM correlates closely with impaired WM structural integrity and thus offers one rational pathologic correlate to diffusion tensor imaging (DTI) parameters

Formation of tilted clusters in the electrochemical deposition of copper on n-gas(001)

Using in-situ synchrotron X-ray diffraction, we have studied the epitaxial properties of Cu clusters electrochemically deposited on n-GaAs(001) substrates. The Cu clusters have (001) base planes and their 〈100〉 directions are aligned with the 〈110〉 directions of the GaAs(001) surface unit cell, but with a large angular spread of 4.5°. Moreover, the Cu(001) planes are tilted with respect to the GaAs(001) substrate. The tilt of about 6° did not show a preference for any substrate azimuth, giving rise to a ring-shaped (111)Cu reflection. This epitaxial tilt seems to be a novel mechanism of strain relief in an epitaxial system with a large mismatch of lattice constants and a large surface roughness

Europäische Leitlinien (S1) für Die Anwendung Von Hochdosierten intravenösen Immunglobulinen in Der Dermatologie

Background and objectives. Treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe cases, the use of immunoglobulin is not generally based on data from randomized controlled trials usually required for evidencebased medicine. Since the indications for the use of IVIg are rare, it is unlikely that such studies will be available in the foreseeable future. Because first-line use is limited by the high costs of IVIg, the first clinical guidelines on the use of IVIg in dermatological conditions were established in 2008 and renewed in 2011. Methods. The European guidelines presented here were prepared by a panel of experts nominated by the European Dermatology Forum (EDF) and European Academy of Dermatology and Venereology (EADV). The guidelines were developed to update the indications for treatment currently considered effective and to summarize the evidence for the use of IVIg in dermatological autoimmune diseases and TEN. Results and conclusion. The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases

Europäische Leitlinien (S1) für die Anwendung von hochdosierten intravenösen Immunglobulinen in der Dermatologie

Hintergrund und Ziele Die Behandlung schwerer dermatologischer Autoimmunerkrankungen und der toxischen epidermalen Nekrolyse (TEN) mit hochdosierten intravenösen Immunglobulinen (IVIg) ist ein bewährtes therapeutisches Verfahren in der Dermatologie. Da eine IVIg‐Therapie in der Regel nur bei seltenen Erkrankungen oder bei schweren Fällen in Betracht gezogen wird, stützt sich die Anwendung von Immunglobulinen zumeist nicht auf Daten aus randomisierten kontrollierten Studien, wie sie in der evidenzbasierten Medizin erforderlich sind. Da Indikationen für die Anwendung von IVIg selten sind, ist es unwahrscheinlich, dass solche Studien in absehbarer Zeit durchgeführt werden. Wegen der hohen Kosten für IVIg im First‐Line‐Einsatz wurden die ersten klinischen Leitlinien für die Anwendung von IVIg bei dermatologischen Erkrankungen im Jahr 2008 herausgegeben und im Jahr 2011 überarbeitet. Methoden Diese europäischen Leitlinien wurden von einer Gruppe durch das EDF und die EADV benannter Experten erarbeitet. Die Leitlinien wurden erstellt, um die derzeit als wirksam erachteten Behandlungsindikationen zu aktualisieren und die für die Anwendung von IVIg bei dermatologischen Autoimmunerkrankungen und TEN vorliegenden Daten zusammenzufassen. Ergebnisse und Schlussfolgerung Die vorliegenden Leitlinien repräsentieren die einvernehmlichen Meinungen und Definitionen von Experten zur Anwendung von IVIg, die die aktuell publizierten Daten widerspiegeln, und sollen als Entscheidungshilfe für den Einsatz von IVIg bei dermatologischen Erkrankungen dienen