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Bottom trawling represents the most widespread anthropogenic physical disturbance to seafloor sediments on continental shelves. While trawling-induced changes to benthic ecology have been widely recognized, the impacts on long-term organic carbon storage in marine sediments remains uncertain. Here we combined datasets of sediment and bottom trawling for a heavily trawled region, the North Sea, to explore their potential mutual dependency. A pattern emerges when comparing the surface sediment organic carbon-to-mud ratio with the trawling intensity represented by the multi-year averaged swept area ratio. The organic carbon-to-mud ratio exhibits a systematic response to trawling where the swept area ratio is larger than 1 yr −1 . Three-dimensional physical–biogeochemical simulation results suggest that the observed pattern is attributed to the correlated dynamics of mud and organic carbon during transport and redeposition in response to trawling. Both gain and loss of sedimentary organic carbon may occur in weakly trawled areas, whereas a net reduction of sedimentary organic carbon is found in intensely trawled grounds. Cessation of trawling allows restoration of sedimentary carbon stock and benthic biomass, but their recovery occurs at different timescales. Our results point out a need for management of intensely trawled grounds to enhance the CO 2 sequestration capacity in shelf seas. Intensive bottom trawling causes a long-term reduction of organic carbon stored in seafloor sediments, suggesting a need for more effective management, according to observations and biogeochemical modelling.

In this paper, we analyse the final decisions for merger cases prepared by the European Commission (EC) since 1990 and build a unique subsample for all non-cleared cases. These incorporate all merger notifications which were either withdrawn by the notifying parties or have been prohibited by the European Commission.We find a sudden decline in prohibitions and withdrawals of cases since 2002 and explore three judicial defeats of the European Commission as determining factors behind these developments. We also find a higher likelihood of withdrawal or prohibition if cases are registered in sectors which incorporate firms in the business of information and communication or transportation and storage. When classifying the documents with a supervised machine learning algorithm, we are able to automatically identify the cleared versus the non-cleared cases with over 90% accuracy. Finally, we find that network effects, high market shares and the risk of collusion are the main competitive concerns which contribute to prohibition decisions in the information and communications sector.

This paper analyses all final merger decisions by the European Commission from the beginning of 1990 up to the end of 2019. We use a novel dataset, containing information about 6245 merger cases from all economic sectors and combining all sorts of decisions, inclusive of withdrawn and prohibited cases. Using text analyses techniques, we first analyse merger decisions documents in order to find trends and differences in language and wording with respect to the 2004 regulation. As a result, we find a shift in favour of terms associated with the More Economic Approach. On the contrary, the concept of dominance has decreased since 2004, indicating a strong decline in structural market parameters for merger reviews. While the tonality is found to be largely positive (especially for cleared cases), again, a change under different merger regimes seems to be evident. Second, accounting for differences in the usage of competition-related terms and by using simple OLS and logit regressions, we find that the duration of the merger review has increased significantly after the 2004 reform. At the same time, the probability of a merger being prohibited has not changed significantly.

We investigate if four leading, electronic news gathering organizations in the US – ABC News, CBS News, FOX News, and NBC News – fulfill their role as the fourth estate in the US democracy. Our analysis, using the Political Coverage Index (PCI) introduced by Dewenter et al (2020), is based on the tonality of their political coverage using 815,000 human-coded news items from 2001 through 2012. For our econometric analysis, we use panel regressions with media and time fixed effects. To account for endogeneity, we cut time spans around national elections out of our data. In the remaining data, elections can be seen as a purely exogenous event. Focusing on the entire media set, we find robust empirical results for an anti-government bias in media reporting: Under Republican presidents, political coverage tends to be more liberal, whereas it tends to be more conservative if the president is a Democrat. However, when focusing on each single news organization, interesting differences emerge: For CBS News and NBC News, we find robust empirical evidence of anti-government-bias. In contrast, FOX News is always much more critical of Democrats than of Republicans. Hence, FOX News can be seen as a more loyal servant to one party rather than acting as the fourth estate. In addition, we find no evidence that ABC News significantly changes its position depending on the presidency. Although descriptive statistics show a certain tendency toward government-critical reporting by ABC News, the variation is not statistically significant.

We investigate if four leading, electronic news gathering organizations in the US - ABC News, CBS News, FOX News, and NBC News - fulfill their role as the fourth estate in the US democracy. Our analysis, using the Political Coverage Index (PCI) introduced by Dewenter et al (2020), is based on the tonality of their political coverage using 815,000 human-coded news items from 2001 through 2012. For our econometric analysis, we use panel regressions with media and time fixed effects. To account for endogeneity, we cut time spans around national elections out of our data. In the remaining data, elections can be seen as a purely exogenous event. Focusing on the entire media set, we find robust empirical results for an anti-government bias in media reporting: Under Republican presidents, political coverage tends to be more liberal, whereas it tends to be more conservative if the president is a Democrat. However, when focusing on each single news organization, interesting differences emerge: For CBS News and NBC News, we find robust empirical evidence of anti-government-bias. In contrast, FOX News is always much more critical of Democrats than of Republicans. Hence, FOX News can be seen as a more loyal servant to one party rather than acting as the fourth estate. In addition, we find no evidence that ABC News significantly changes its position depending on the presidency. Although descriptive statistics show a certain tendency toward government-critical reporting by ABC News, the variation is not statistically significant.

Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources of [ 18 F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients. First, we conducted a longitudinal [ 18 F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and detected elevated [ 18 F]PI-2620 PET signals in the presence of high levels of neuronal tau. An innovative approach involving cell sorting after radiotracer injection in vivo revealed higher tracer uptake in single neurons than in the astrocytes of PS19 mice. Regional [ 18 F]PI-2620 tau PET signals during the lifetime correlated with the abundance of fibrillary tau and with autoradiography signal intensity in PSP patients and disease controls who underwent autopsy 2–63 months after tau PET. In autoradiography, tau-positive neurons and oligodendrocytes with a high AT8 density, but not tau-positive astrocytes, were the drivers of [ 18 F]PI-2620 autoradiography signals in individuals with PSP. The high tau abundance in oligodendrocytes at the boundary of gray and white matter facilitated the identification of an optimized frontal lobe target region to detect the tau burden in patients with PSP. In summary, neuronal and oligodendroglial tau constitutes the dominant source of tau PET radiotracer binding in 4-repeat-tauopathies, translating to an in vivo signal.

PurposeLittle is known about the effect of SARS-CoV-2 infection on glioblastoma (GBM) growth, metabolism, and prognosis. Immunological changes within GBM tissue are potentially symptomatic, underlining the urgent need for a better understanding of this phenomenon. To date, the complex underlying biology has not been fully elucidated. A decisive role of the tumor microenvironment (TME) and the components of the immune system acting within it is assumed.MethodsImmunohistochemical staining of SARS-CoV-2 spike protein and immune cell infiltration of TME was performed on the tumor tissue of one patient. This patient developed hemiparesis 14 days after symptomatic SARS-CoV-2 infection, leading to tumor diagnosis. Subsequently and after biopsy, there was an unexpectedly good response to chemotherapy only. In looking for further evidence of the potential of SARS-CoV-2 to influence the course of GBM, two additional adult patients that had transient MRI changes and neurological deterioration following SARS-CoV-2 infection were evaluated.ResultsIn the patient for whom neurological deterioration in the course of SARS-CoV-2 led to GBM diagnosis, immunohistochemistry revealed virus-specific protein accumulation in the tumor cells, microglial activation, and the formation of T-cell nodules. In the other two patients, the findings were compatible with symptomatic pseudoprogression that occurred in a temporal relationship with SARS-CoV-2 infection.ConclusionThe results indicate a possible association between clinically relevant changes in GBM biology and SARS-CoV-2 infection, with histological confirmation of SARS-CoV-2-associated changes within the tumor tissue. The exact pathomechanism and underlying inflammatory pathways require further investigation.

Ketamine is the first glutamatergic agent in clinical use for major depression, but its primary target remains unclear. Further research is needed to develop more specific interventions with fewer side effects. Ketamine is a noncompetitive antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor. Here, we show that ketamine preferentially targets GluN2D-containing NMDA receptors on interneurons, and that selective GluN2D antagonism is sufficient to produce rapid antidepressant-like effects. We use ketamine, the selective GluN2C/D inhibitor NAB-14, Grin2d -siRNA and chemogenetic approaches in hippocampal slices and in vivo mice. We find that GluN2D antagonism inhibits NMDAR currents in interneurons but not pyramidal cells, and that GluN2D-mediated recruitment of GABAergic interneurons controls inhibitory circuits regulating hippocampal activity and plasticity. In a mouse model of depression, GluN2D inhibition recovers excitation-inhibition balance, restores plasticity, and mimics antidepressant-like actions of ketamine with fewer side effects. These findings identify GluN2D as a highly specific target for novel antidepressant therapy. Here authors identify GluN2D-containing NMDA receptors on interneurons as a specific target for rapid antidepressant action. Blocking GluN2D restores stress-impaired plasticity and mimics the effects of ketamine with fewer side effects.

Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson’s Disease (PD) are in early phases of clinical testing. Involving patients’ preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects. Demonstrating a non-gaussian distribution, risk willingness varied markedly within, and between groups. MSA patients accepted a median 1% risk [interquartile range: 0.001–25%] of sudden death for a 99% [interquartile range: 99.999–75%] chance of cure, while PD patients reported a median 0.055% risk [interquartile range: 0.001–5%]. Contrary to our hypothesis, a considerable proportion of MSA patients, despite their substantially impaired quality of life, were not willing to accept increased therapy-associated risks. Satisfaction with life situation, emotional, and nonmotor disease burden were associated with MSA patients’ risk willingness in contrast to PD patients, for whom age, and disease duration were associated factors. An individual approach towards MSA and PD patients is crucial as direct inference from disease (stage) to therapy-associated risk willingness is not feasible. Such studies may be considered by regulatory agencies in their approval processes assisting with the weighting of safety aspects in a patient-centric manner. A systematic quantitative assessment of patients’ risk willingness and associated features may assist physicians in conducting individual consultations with patients who have MSA or PD by facilitating communication of risks and benefits of a treatment option.

Tau-PET receives growing interest as an imaging biomarker for the 4-repeat tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau-PET signals is still unclear. Therefore, we conducted a longitudinal [18F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and found elevated [18F]PI-2620 PET signal in the presence of high neuronal tau. Cell sorting after radiotracer injection in vivo revealed higher tracer uptake in single neurons compared to astrocytes of PS19 mice. Regional [18F]PI-2620 tau-PET signals during lifetime correlated with abundance of fibrillary tau in subsequent autopsy samples of PSP patients and disease controls. In autoradiography, tau-positive neurons and oligodendrocytes with high AT8 density but not tau-positive astrocytes were the driver of [18F]PI-2620 autoradiography signals in PSP. In summary, neuronal and oligodendroglial tau constitutes the dominant source of tau-PET radiotracer binding in 4-repeat-tauopathies, yielding the capacity to translate to an in vivo signal.