Investigating the post-stimulus undershoot of the BOLD signal – A simultaneous fMRI and fNIRS study

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Near-infrared spectroscopy can detect brain activity during a color-word matching Stroop task in an event-related design

Brai nactivit ycanbemonitore dnon-invasivel ybynear-infrare dspectroscop y(NIRS) ,whic hhas severa ladvantage sincompariso nwit hothe rimagin gmethods ,suc hasflexibility ,portability ,low cost an dbiochemica lspecificity .Moreover ,patient san dchildre ncanberepetitivel yexamined .Therefore ,the objectiv eofthestud ywa stotes tthefeasibilit yofNIR Sfortheevent-relate dapproac hinfunctiona lbrain activatio nstudie swit hcognitiv eparadigms .Thus ,change sintheconcentratio nofoxy- ,deoxy- ,an dtotal hemoglobi nwer emeasure d byNIR Sin14health ysubject swhil eperformin ga color–wor d matching Stroo p tas k in an event-relate d design .Th ehemodynami crespons e(increas ein theconcentratio n of oxy-/tota lhemoglobi n an d decreas ein theconcentratio n ofdeoxy-hemoglobin )wa sstronge rduring incongruen tcompare dtocongruen tan dneutra ltrial softheStroo ptas kinthelatera lprefronta lcortex bilaterally .Thi sstronge rhemodynami crespons ewa sinterprete dasa stronge rbrai nactivatio nduring incongruen ttrial softheStroo ptask ,du etointerference .A ne w metho dforNIR Sdat aevaluatio nthat enable stheanalysi softhehemodynami crespons etoeac hsingl etria lisintroduced .Eac hhemodynamic respons ewa scharacterize dbytheparameter sgain ,lagan ddispersio nofa Gaussia nfunctio nfitte dby nonlinea rregression .Specifi cdifference sbetwee ntheincongruen tan dneutra lconditio nwer efoun dfor gai nan dlag .Further ,thes eparameter swer ecorrelate dwit hthebehaviora lperformance .Inconclusion, brai nactivit yma ybestudie d byNIR Susin gcognitiv estimul iinanevent-relate d design

Coevolution of alliance portfolio and organization of new technology-based firms: A case study of the Mobile Internet industry

Coevolution of alliance portfolios and organizations: A cross sector analysis of new technology based firms in the European Mobile Internet industry / Tillmann von Schroeter, EXIST-HighTEPP at the University of Bamberg. Strategic alliances and partnerships have extensively been studied over the past twenty years. Research has shown that they are a way to gain resources in a cost-efficient manner, especially for new firms with limited resources. In addition, alliances can help to spread technological development risks. One may conclude, that for new technology-based firms (NTBF) strategic alliances are a logical and timely response to intense and rapid changes in economic and technological environments. Given that the benefits of a partnership change over time, it is difficult however, to determine how the optimal alliance portfolio should be structured. NTBFs frequently face the problem that some partnerships in their alliance portfolio (defined as the collection of all partnerships) are not efficient (defined as time and resources devoted over the received benefits). Therefore, it is important on one hand to understand how benefits are derived from an alliance portfolio and what its impact on the organizational development is. On the other hand, it is critical to recognize the superior forces, which drive the alliance portfolio dynamics. One partnership intensive industry, which is both high-tech and entrepreneurial, is Mobile Internet. Four forces - high levels of required investments, changing industry barriers, significant dependencies due to a highly integrated value chain, and fast technological innovations - largely explain why this is the case. This study analyzes how alliance portfolios influence the organizational development of NTBF’s in this industry, and what impact an efficiently managed alliance portfolio has on company performance. In addition, it researches if organizational changes trigger structural changes concerning the alliance portfolio and, therefore, its dynamics. The research is based on nine in-depth case studies selected from three sectors of the mobile Internet industry and comprises three major steps: (1) Industry analyses based on secondary data (industry reports and white papers), conferences, and preparatory interviews with industry experts such as mobile operators and consultants. (2) Company analyses based on secondary data including annual reports, press clippings, Internet sites, and databases such as Factiva, OneSource, and Hoover's. (3) Two-hour face-to-face interviews with one or two founders or managers from the companies, with follow-up telephone interviews on specific questions. In summary, 400 pages of interview transcripts, 5,000 pages of corporate information and 15 industry reports are the basis of this study. A profile has been established for each company showing its organizational development over time (characteristics such as its structure, management style, and resource requirements), its alliance portfolio (partnership foundation, degree of intensity) and its performance (survival, revenue development, profits and employees, and awards as a proxy for technological achievements). The efficiency of alliance portfolios is analyzed by comparing resource requirements with the shape of the alliance portfolio at every development stage. Pajec, a software tool to analyze large social networks, supports this analysis. The research on alliances has focused more on dyadic relationships than on alliance portfolios. This explains why later research suffers from the deficiency that the process of alliance portfolio formation and transformation has not been fully addressed. Although recent studies have stressed the portfolio approach, they have predominantly assessed static scenarios. The impact of organizational development stages on the alliance portfolio structure remains largely undiscovered. The contribution of this research, offering an extensive analysis of the alliances of NTBFs in the European Mobile Internet industry, is twofold: (1) Life cycle approaches, the RBV, and network theory (approaches which have until now been regarded separately most of the time) are linked into one comprehensive model. This model adds to the underdeveloped area of the dynamics of alliances. It contains the - time-dependent - aspect of alliance portfolio efficiency by comparing NTBF's portfolio structure with its resource requirements depending on the position in its life cycle. (2) It provides managers of NTBFs with a tool to structure and manage their alliance portfolio pro-actively.Entwicklung von Allianz-Netzwerk und Organisation bei jungen Technologiefirmen: Eine Fallstudie der gegenseitigen Beeinflussung von externer und interner Organisation in der Mobile-Internet Industrie / Tillmann von Schroeter, EXIST-HighTEPP an der Universität Bamberg. Strategische Allianzen und Partnerschaften wurden in den letzten zwanzig Jahren intensiv untersucht. Die Forschung zeigt auf, dass insbesondere für Firmen mit begrenzten Finanzmitteln Allianzen eine Option sind, um kosteneffizient Ressourcen zu erlangen. Darüber hinaus können sie dazu dienen, technologische Risiken auf mehrere Schultern zu verteilen, um somit diese für einzelne Firmen zu reduzieren. Hieraus lässt sich schließen, dass für neue technologie-basierte Firmen (NTBF) strategische Allianzen eine logische Reaktion darstellen, auf den schnellen Wandel im wirtschaftlichen und technologischen Umfeld zu reagieren. Was auch immer die Allianzgründe motiviert, der Nutzen einer Partnerschaft ändert sich mit der Zeit. Daher ist es schwierig zu bestimmen, wie das optimale Allianz-Portfolio (definiert als die Summe aller Partnerschaften) strukturiert sein sollte. NTBF sind häufig mit dem Problem konfrontiert, dass einige Partnerschaften nicht effizient sind (investierte Zeit/Ressourcen bezogen auf den erreichten Nutzen). Von daher ist es zum einen notwendig zu verstehen, welcher Nutzen aus dem Allianz-Portfolio entsteht und welchen Einfluss dieser auf die Entwicklung der Firma hat. Zum andern ist es wichtig zu erkennen, welche übergelagerten Kräfte die Dynamik des Allianz-Portfolios bestimmen. Eine Allianz-intensive Industrie - sowohl technologie-basiert als auch unternehmerisch geprägt - ist das Mobile Internet. Vier Treiber - hohe Kapitalintensität, sich verändernde Industriebarrieren, hohe Abhängigkeiten aufgrund von stark integrierten Wertschöpfungs-ketten und kurze Innovationszyklen - erklären weitestgehend, warum dies der Fall ist. Diese Studie analysiert, wie in dieser Industrie Allianz-Portfolien die organisatorische Entwicklung von NTBF beeinflussen, und welchen Einfluss ein effizient geführtes Allianz-Portfolio auf die Leistungsfähigkeit des Unternehmens hat. Zusätzlich wurde innerhalb der Studie untersucht, ob ein organisatorischer Wandel - und wenn ja welcher - Veränderungen innerhalb des Allianz-Portfolios anstößt und somit dessen Dynamik beeinflusst. Die Forschungsstudie basiert auf neun detaillierten Fallstudien aus drei Segmenten der Mobile-Internet Industrie, die in drei Schritten erarbeitet wurden: (1) Industrieanalyse basierend auf Sekundärdaten (Industrie Reports und White Papers), Konferenzen sowie vorbereitende Interviews mit Industrieexperten wie z. B. Mobilfunk-betreiber und spezialisierten Beratern. (2) Firmenanalysen basierend auf Sekundärdaten wie Jahresabschlüsse, Pressemitteilungen, Internet-Seiten und Datenbanken wie Factiva, OneSource und Hoover's. (3) Zwei- bis dreistündige, persönliche Interviews mit ein oder zwei Gründern/Managern der Firmen sowie sich anschließende Telefoninterviews, um spezifische Fragen im Nachgang zu klären. Zusammenfassend bilden über 400 Seiten Interviewprotokolle, 5,000 Seiten Firmeninformationen sowie 15 Industrie Reports die Grundlage für diese Studie. Darauf aufbauend wurde für jede Fallstudien-Firma ein Profil erstellt, das deren organisatorischen Wandel (charakterisiert durch Organisationsstruktur, Führungsstil und -team sowie Ressourcenbedarf je Entwicklungsschritt), deren Allianz-Portfolio (je Partnerschaft Gründungsdatum, Motivation und Intensität über die Zeit) und deren Leistungsfähigkeit (Wachstum gemessen in Umsatz- sowie Mitarbeiterentwicklung, Ertragskraft sowie Auszeichnungen als ein Proxy für die technologische Leistungsfähigkeit) umfasst. Die Effizienz des Allianz-Portfolios wurde analysiert, indem der Ressourcenbedarf der NTBF je Entwicklungsschritt mit der Ressourcenbereitstellung aus dem Allianzportfolio (bewertet durch dessen Struktur) abgeglichen wurde. Pajec, eine Software zur Analyse größerer sozialer Netzwerke, unterstützte diese Analyse. Die bisherige Allianzforschung war - und ist immer noch - stärker fokussiert auf dyadischen Beziehungen als auf ganze Allianzportfolien. Dies erklärt, warum diese Forschung Defizite in der Erklärung von Portfilioentstehungs- und Transformationsprozessen aufweist. Obwohl neuere Studien stärker Allianz-Portfolien betrachtet haben, wurden vorherrschend statische Szenarien untersucht. Der Einfluss von organisatorischen Entwicklungsschritten auf die Struktur von Allianzportfolien blieb noch weitgehend unerforscht. Der Beitrag dieser Forschungsarbeit, der eine breit angelegte Allianzanalyse von NTBF in der europäischen Mobile Internet Industrie zugrunde liegt, ist zweigestalt: (1) Lebenszyklus-modelle, der Resource-Based-Few (RBV) und Netzwerk-Theorie (wissenschaftliche Ansätze, die bisher meistens separat betrachtet wurden) wurden integriert und in einem umfassenden Modell miteinander verknüpft. Dieses Modell erweitert das noch (zu) wenig erforschte Gebiet der Allianzdynamik. Es umfasst die zeit-/entwicklungsphasenabhängigen Aspekte der Allianz-Portfolio-Effizienz indem die Portfoliostruktur mit dem Ressourcenbedarf je Entwicklungsphase abgeglichen wird. (2) NTBF- Manager erhalten ein Werkzeug, um deren Allianz-Portfolio zu strukturieren und pro-aktiv zu steuern

Correlation of cognitive status, MRI- and SPECT-imaging in CADASIL patients

Although there is evidence for correlations between disability and magnetic resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of structural MRI abnormalities for cognitive dysfunction remains controversial. We performed detailed neuropsychological testing, high resolution MRI, and Tc-99m-ethyl cysteinate-dimer SPECT in three CADASIL patients. MR-images were rated independently by two investigators for the presence of white matter lesions, lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was quantified by the use of automatic morphometric assessment of the cortical thickness. In addition, laboratory and patients' history data were collected in order to assess the individual vascular risk factor profile. The differences in cognitive performance between the three patients are neither explained by structural-, or functional neuroimaging, nor by the patient-specific vascular risk factor profiles. The neuroradiologically least affected patient met criteria for dementia, whereas the most severely affected patient was in the best clinical and cognitive state. Conventional structural and functional neuroimaging is important for the diagnosis of CADASIL, but it is no sufficient surrogate marker for the associated cognitive decline. Detailed neuropsychological assessment seems to be more useful, particularly with respect to the implementation of reliable outcome parameters in possible therapeutic trials

Is implantable cardioverter defibrillator surgery in patients with an implanted left ventricular assist device safe under uninterrupted oral anticoagulation?

Abstract Background: Implantable cardioverter-defibrillator (ICD) surgery in patients with implanted left ventricular assist devices (LVAD) is associated with an increased risk of bleeding complications because of the need to ensure that these patients are adequately anticoagulated. Our study aimed to evaluate the safety of our new strategy of uninterrupted oral anticoagulation compared to heparin-bridging during the surgical interval. Methods: Between January 2009 and January 2020, 116 patients with LVAD underwent ICD surgery. Since January 2015, 60 patients were operated under continued sufficient oral anticoagulation with a vitamin k antagonist (VKA group). Fifty-six patients underwent a heparin-bridging regimen (heparin group). Demographics, perioperative data, complications, and mortality were analyzed. Results: Bleeding complications attributable to the surgical intervention occurred more often (19.6% vs. 10.0%, p = 0.142) and at a higher rate of re-exploratory surgery (14.3% vs. 5.0%, p = 0.088) in the heparin group without reaching statistical significance. Moreover, the heparin group patients' postoperative total length of stay was 10 days longer (17.8 ± 23.8 days vs. 8.3 ± 9.5 days, p = 0.007). There were no procedure-related deaths, no thromboembolic events, and no LVAD-related thrombosis. Conclusion: Our strategy of uninterrupted oral anticoagulation is safe and results in a reduction by more than half the number of days in hospital without an increase in adverse events

The thermal limits to life on Earth

Living organisms on Earth are characterized by three necessary features: a set of internal instructions encoded in DNA (software), a suite of proteins and associated macromolecules providing a boundary and internal structure (hardware), and a flux of energy. In addition, they replicate themselves through reproduction, a process that renders evolutionary change inevitable in a resource-limited world. Temperature has a profound effect on all of these features, and yet life is sufficiently adaptable to be found almost everywhere water is liquid. The thermal limits to survival are well documented for many types of organisms, but the thermal limits to completion of the life cycle are much more difficult to establish, especially for organisms that inhabit thermally variable environments. Current data suggest that the thermal limits to completion of the life cycle differ between the three major domains of life, bacteria, archaea and eukaryotes. At the very highest temperatures only archaea are found with the current high-temperature limit for growth being 122 °C. Bacteria can grow up to 100 °C, but no eukaryote appears to be able to complete its life cycle above ∼60 °C and most not above 40 °C. The lower thermal limit for growth in bacteria, archaea, unicellular eukaryotes where ice is present appears to be set by vitrification of the cell interior, and lies at ∼−20 °C. Lichens appear to be able to grow down to ∼−10 °C. Higher plants and invertebrates living at high latitudes can survive down to ∼−70 °C, but the lower limit for completion of the life cycle in multicellular organisms appears to be ∼−2 °

Microbial community functioning during plant litter decomposition

International audienceAbstract Microbial life in soil is fueled by dissolved organic matter (DOM) that leaches from the litter layer. It is well known that decomposer communities adapt to the available litter source, but it remains unclear if they functionally compete or synergistically address different litter types. Therefore, we decomposed beech, oak, pine and grass litter from two geologically distinct sites in a lab-scale decomposition experiment. We performed a correlative network analysis on the results of direct infusion HR-MS DOM analysis and cross-validated functional predictions from 16S rRNA gene amplicon sequencing and with DOM and metaproteomic analyses. Here we show that many functions are redundantly distributed within decomposer communities and that their relative expression is rapidly optimized to address litter-specific properties. However, community changes are likely forced by antagonistic mechanisms as we identified several natural antibiotics in DOM. As a consequence, the decomposer community is specializing towards the litter source and the state of decomposition (community divergence) but showing similar litter metabolomes (metabolome convergence). Our multi-omics-based results highlight that DOM not only fuels microbial life, but it additionally holds meta-metabolomic information on the functioning of ecosystems

Successful Treatment of Myasthenia Gravis Following PD-1/CTLA-4 Combination Checkpoint Blockade in a Patient With Metastatic Melanoma

Currently, the blockade of certain immune checkpoints such as the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) using checkpoint inhibitors is standard of care in patients with metastatic melanoma, especially with BRAF wild-type. However, several checkpoint inhibitor-related complications have been reported, including severe adverse events in the central and peripheral nervous system. In particular, in the recent past, the occurrence of myasthenia gravis following checkpoint inhibitor monotherapy, particularly nivolumab or ipilimumab, has been reported. In contrast, reports on PD-1/CTLA-4 combination blockade—usually with fatal clinical outcome—are scarce. We here report a case with combination immune checkpoint blockade-related myasthenia gravis with favorable clinical outcome

A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (

The Inflammatory Response After Ischemic Stroke: Targeting β\u3csub\u3e2\u3c/sub\u3e and β\u3csub\u3e1\u3c/sub\u3e Integrins

Ischemic stroke is a leading cause of death and disability with limited therapeutic options. Resulting inflammatory mechanisms after reperfusion (removal of the thrombus) result in cytokine activation, calcium influx, and leukocytic infiltration to the area of ischemia. In particular, leukocytes migrate toward areas of inflammation by use of integrins, particularly integrins β1 and β2. Integrins have been shown to be necessary for leukocyte adhesion and migration, and thus are of immediate interest in many inflammatory diseases, including ischemic stroke. In this review, we identify the main integrins involved in leukocytic migration following stroke (αLβ2, αDβ2, α4β1, and α5β1) and targeted clinical therapeutic interventions