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The brain's structural network follows a hierarchy that is described as rich club (RC) organization, with RC hubs forming the well-interconnected top of this hierarchy. In this study, we tested whether RC hubs are involved in the processing of hierarchically higher structures in stimulus sequences. Moreover, we explored the role of previously suggested cortical gradients along anterior-posterior and medial-lateral axes throughout the frontal cortex. To this end, we conducted a functional magnetic resonance imaging (fMRI) experiment and presented participants with blocks of digit sequences that were structured on different hierarchically nested levels. We additionally collected diffusion weighted imaging data of the same subjects to identify RC hubs. This classification then served as the basis for a region of interest analysis of the fMRI data. Moreover, we determined structural network centrality measures in areas that were found as activation clusters in the whole-brain fMRI analysis. Our findings support the previously found anterior and medial shift for processing hierarchically higher structures of stimuli. Additionally, we found that the processing of hierarchically higher structures of the stimulus structure engages RC hubs more than for lower levels. Areas involved in the functional processing of hierarchically higher structures were also more likely to be part of the structural RC and were furthermore more central to the structural network. In summary, our results highlight the potential role of the structural RC organization in shaping the cortical processing hierarchy., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The permafrost region has accumulated organic carbon in cold and waterlogged soils over thousands of years and now contains three times as much carbon as the atmosphere. Global warming is degrading permafrost with the potential to accelerate climate change as increased microbial decomposition releases soil carbon as greenhouse gases. A 19-year time series of soil and ecosystem respiration radiocarbon from Alaska provides long-term insight into changing permafrost soil carbon dynamics in a warmer world. Nine per cent of ecosystem respiration and 23% of soil respiration observations had radiocarbon values more than 50‰ lower than the atmospheric value. Furthermore, the overall trend of ecosystem and soil respiration radiocarbon values through time decreased more than atmospheric radiocarbon values did, indicating that old carbon degradation was enhanced. Boosted regression tree analyses showed that temperature and moisture environmental variables had the largest relative influence on lower radiocarbon values. This suggested that old carbon degradation was controlled by warming/permafrost thaw and soil drying together, as waterlogged soil conditions could protect soil carbon from microbial decomposition even when thawed. Overall, changing conditions increasingly favoured the release of old carbon, which is a definitive fingerprint of an accelerating feedback to climate change as a consequence of warming and permafrost destabilization. This article is part of the Theo Murphy meeting issue 'Radiocarbon in the Anthropocene'.

Permafrost thaw causes the seasonally thawed active layer to deepen, causing the Arctic to shift toward carbon release as soil organic matter becomes susceptible to decomposition. Ground subsidence initiated by ice loss can cause these soils to collapse abruptly, rapidly shifting soil moisture as microtopography changes and also accelerating carbon and nutrient mobilization. The uncertainty of soil moisture trajectories during thaw makes it difficult to predict the role of abrupt thaw in suppressing or exacerbating carbon losses. In this study, we investigated the role of shifting soil moisture conditions on carbon dioxide fluxes during a 13-year permafrost warming experiment that exhibited abrupt thaw. Warming deepened the active layer differentially across treatments, leading to variable rates of subsidence and formation of thermokarst depressions. In turn, differential subsidence caused a gradient of moisture conditions, with some plots becoming consistently inundated with water within thermokarst depressions and others exhibiting generally dry, but more variable soil moisture conditions outside of thermokarst depressions. Experimentally induced permafrost thaw initially drove increasing rates of growing season gross primary productivity (GPP), ecosystem respiration (R eco ), and net ecosystem exchange (NEE) (higher carbon uptake), but the formation of thermokarst depressions began to reverse this trend with a high level of spatial heterogeneity. Plots that subsided at the slowest rate stayed relatively dry and supported higher CO 2 fluxes throughout the 13-year experiment, while plots that subsided very rapidly into the center of a thermokarst feature became consistently wet and experienced a rapid decline in growing season GPP, R eco , and NEE (lower carbon uptake or carbon release). These findings indicate that Earth system models, which do not simulate subsidence and often predict drier active layer conditions, likely overestimate net growing season carbon uptake in abruptly thawing landscapes., (© 2023 John Wiley & Sons Ltd.)

Background: Controllability is a measure of the brain's ability to orchestrate neural activity which can be quantified in terms of properties of the brain's network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to long-lasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging., Methods: In a sample of 814 healthy individuals (aged 33.9 ± 12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability)., Results and Conclusion: In nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jamalabadi, Hahn, Winter, Nozari, Ernsting, Meinert, Leehr, Dohm, Bauer, Pfarr, Stein, Thomas-Odenthal, Brosch, Mauritz, Gruber, Repple, Kaufmann, Krug, Nenadić, Kircher, Dannlowski and Derntl.)

Background: Cognitive dysfunction and brain structural connectivity alterations have been observed in major depressive disorder (MDD). However, little is known about their interrelation. The present study follows a network approach to evaluate alterations in cognition-related brain structural networks., Methods: Cognitive performance of n = 805 healthy and n = 679 acutely depressed or remitted individuals was assessed using 14 cognitive tests aggregated into cognitive factors. The structural connectome was reconstructed from structural and diffusion-weighted magnetic resonance imaging. Associations between global connectivity strength and cognitive factors were established using linear regressions. Network-based statistics were applied to identify subnetworks of connections underlying these global-level associations. In exploratory analyses, effects of depression were assessed by evaluating remission status-related group differences in subnetwork-specific connectivity. Partial correlations were employed to directly test the complete triad of cognitive factors, depressive symptom severity, and subnetwork-specific connectivity strength., Results: All cognitive factors were associated with global connectivity strength. For each cognitive factor, network-based statistics identified a subnetwork of connections, revealing, for example, a subnetwork positively associated with processing speed. Within that subnetwork, acutely depressed patients showed significantly reduced connectivity strength compared to healthy controls. Moreover, connectivity strength in that subnetwork was associated to current depressive symptom severity independent of the previous disease course., Conclusions: Our study is the first to identify cognition-related structural brain networks in MDD patients, thereby revealing associations between cognitive deficits, depressive symptoms, and reduced structural connectivity. This supports the hypothesis that structural connectome alterations may mediate the association of cognitive deficits and depression severity.

B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19 + B-cell compartment was significantly decreased in PCa patients and dominated by naïve B cells. The nodal B-cell compartment had significantly increased fractions of CD19 + B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.

Background: Altered brain structural connectivity has been implicated in the pathophysiology of psychiatric disorders including schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). However, it is unknown which part of these connectivity abnormalities are disorder specific and which are shared across the spectrum of psychotic and affective disorders. We investigated common and distinct brain connectivity alterations in a large sample (N = 1743) of patients with SZ, BD, or MDD and healthy control (HC) subjects., Methods: This study examined diffusion-weighted imaging-based structural connectome topology in 720 patients with MDD, 112 patients with BD, 69 patients with SZ, and 842 HC subjects (mean age of all subjects: 35.7 years). Graph theory-based network analysis was used to investigate connectome organization. Machine learning algorithms were trained to classify groups based on their structural connectivity matrices., Results: Groups differed significantly in the network metrics global efficiency, clustering, present edges, and global connectivity strength with a converging pattern of alterations between diagnoses (e.g., efficiency: HC > MDD > BD > SZ, false discovery rate-corrected p = .028). Subnetwork analysis revealed a common core of edges that were affected across all 3 disorders, but also revealed differences between disorders. Machine learning algorithms could not discriminate between disorders but could discriminate each diagnosis from HC. Furthermore, dysconnectivity patterns were found most pronounced in patients with an early disease onset irrespective of diagnosis., Conclusions: We found shared and specific signatures of structural white matter dysconnectivity in SZ, BD, and MDD, leading to commonly reduced network efficiency. These results showed a compromised brain communication across a spectrum of major psychiatric disorders., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The technology driven post-scarcity society is upon us. Ubiquitous technologies are eradicating scarcity in many industries. These macroscopic system trends are causing our economy to transition from relative scarcity to relative abundance. For many people in the world however, in both developed, developing, and underdeveloped countries, the notion of an Age of Abundance will sound utterly bizarre. There is a tension between abundance and equality. Good governance considers in what manner the state conducts public policy, manages public resources and promotes overall prosperity. This chapter connects good governance to the end of scarcity and integrates equality into abundance. The chapter critically examines the normative justifications of our scarcity based legal institutions, such as property and intellectual property (IP) systems, in light of 10 exponential, Fourth Industrial Revolution (4IR) technologies, and the post-scarcity economy. Starting point is that absolute and relative abundance are not utopian. Technology will erase scarcity in more and more economic areas in the foreseeable future, but not everywhere or for everybody. The chapter views relative scarcity and relative abundance as temporal socio-economic categories at two opposite sides of a continuum. The chapter unifies good governance with equality and abundance, by introducing a post-Rawlsian Equal Relative Abundance (ERA) principle of distributive justice. This includes defining a set of material and immaterial primary goods, warranting adequate, sufficient levels of relative abundance (which depend on technological evolution), and equitable results per region or group. Crucially, ERA integrates desert-based principles to the degree that some may deserve a higher level of material goods because of inequality in contributions, i.e., their hard work, talent, luck or entrepreneurial spirit, only to the extent that their unequal rewards do also function to improve the position of the least advantaged. A society governed by the ERA principle should in theory be able to solve the poverty trap on a global level. As lifting people from poverty in Europe is a different thing than achieving ERA in the US, applying equal relative abundance techniques in Asia and Africa each have their own specific challenges and dimensions., Competing Interests: Author MK was employed by AIRecht. The handling editor ML declared a shared affiliation with the author at the time of review., (Copyright © 2022 Kop.)

Machine Learning has become more important for materials engineering in the last decade. Globally, automated machine learning (AutoML) is growing in popularity with the increasing demand for data analysis solutions. Yet, it is not frequently used for small tabular data. Comparisons and benchmarks already exist to assess the qualities of AutoML tools in general, but none of them elaborates on the surrounding conditions of materials engineers working with experimental data: small datasets with less than 1000 samples. This benchmark addresses these conditions and draws special attention to the overall competitiveness with manual data analysis. Four representative AutoML frameworks are used to evaluate twelve domain-specific datasets to provide orientation on the promises of AutoML in the field of materials engineering. Performance, robustness and usability are discussed in particular. The results lead to two main conclusions: First, AutoML is highly competitive with manual model optimization, even with little training time. Second, the data sampling for train and test data is of crucial importance for reliable results., (© 2022. The Author(s).)

Several recent studies have argued that large, long-lived and molten magma chambers may not occur in the shallow Earth's crust. Here we present, however, field-based observations from the Bushveld Complex that provide evidence to the contrary. In the eastern part of the complex, the magmatic layering continuously drapes across a ~ 4-km-high sloping step in the chamber floor. Such deposition of magmatic layering implies that the resident melt column was thicker than the stepped relief of the chamber floor. Prolonged internal differentiation within this thick magma column is further supported by evolutionary trends in crystallization sequence and mineral compositions through the sequence. The resident melt column in the Bushveld chamber during this period is estimated at > 5-km in thickness and > 380,000 km 3 in volume. This volume of magma is three orders of magnitude larger than any known super-eruption in the Earth's history and is only comparable to the extrusive volumes of some of Earth's large igneous provinces. This suggests that super-large, entirely molten, and long-lived magma chambers occur, at least occasionally, in the geological history of our planet. Therefore, the classical view of magma chambers as 'big magma tanks' remains a viable research concept for some of Earth's magmatic provinces., (© 2022. The Author(s).)

Importance: Identifying neurobiological differences between patients with major depressive disorder (MDD) and healthy individuals has been a mainstay of clinical neuroscience for decades. However, recent meta-analyses have raised concerns regarding the replicability and clinical relevance of brain alterations in depression., Objective: To quantify the upper bounds of univariate effect sizes, estimated predictive utility, and distributional dissimilarity of healthy individuals and those with depression across structural magnetic resonance imaging (MRI), diffusion-tensor imaging, and functional task-based as well as resting-state MRI, and to compare results with an MDD polygenic risk score (PRS) and environmental variables., Design, Setting, and Participants: This was a cross-sectional, case-control clinical neuroimaging study. Data were part of the Marburg-Münster Affective Disorders Cohort Study. Patients with depression and healthy controls were recruited from primary care and the general population in Münster and Marburg, Germany. Study recruitment was performed from September 11, 2014, to September 26, 2018. The sample comprised patients with acute and chronic MDD as well as healthy controls in the age range of 18 to 65 years. Data were analyzed from October 29, 2020, to April 7, 2022., Main Outcomes and Measures: Primary analyses included univariate partial effect size (η2), classification accuracy, and distributional overlapping coefficient for healthy individuals and those with depression across neuroimaging modalities, controlling for age, sex, and additional modality-specific confounding variables. Secondary analyses included patient subgroups for acute or chronic depressive status., Results: A total of 1809 individuals (861 patients [47.6%] and 948 controls [52.4%]) were included in the analysis (mean [SD] age, 35.6 [13.2] years; 1165 female patients [64.4%]). The upper bound of the effect sizes of the single univariate measures displaying the largest group difference ranged from partial η2 of 0.004 to 0.017, and distributions overlapped between 87% and 95%, with classification accuracies ranging between 54% and 56% across neuroimaging modalities. This pattern remained virtually unchanged when considering either only patients with acute or chronic depression. Differences were comparable with those found for PRS but substantially smaller than for environmental variables., Conclusions and Relevance: Results of this case-control study suggest that even for maximum univariate biological differences, deviations between patients with MDD and healthy controls were remarkably small, single-participant prediction was not possible, and similarity between study groups dominated. Biological psychiatry should facilitate meaningful outcome measures or predictive approaches to increase the potential for a personalization of the clinical practice.

Background: Anhedonia is a key symptom of major depressive disorder (MDD). Anhedonia is associated with aberrant reward processing, but whether it might interfere similarly with the neural processing of aversive stimuli, such as monetary loss, remains unknown. We aimed to investigate potential associations between anhedonia and neural response during reward and loss processing in patients with MDD., Methods: We investigated blood-oxygen-level-dependent response in the orbitofrontal cortex, cingulate cortex, insula and basal ganglia during monetary reward and loss processing in 182 patients with MDD, using a card-guessing paradigm. We measured anhedonia with the Social and Physical Anhedonia Scale (SASPAS), and we tested for the main and interaction effects of SASPAS scores and the experimental condition (reward or loss) in a full factorial model., Results: We detected a negative main effect of anhedonia, as well as a significant interaction effect of anhedonia and the experimental condition, on orbitofrontal and insular neural response. Post hoc analyses revealed that the interaction was driven by a significant association between higher anhedonia scores and hypoactivation during loss processing. We observed no significant association between anhedonia and neural response during reward processing., Limitations: This study had a cross-sectional design., Conclusion: Our findings confirmed that altered neural processing in the orbitofrontal cortex and insula is a neurobiological feature of anhedonic symptomatology in people with MDD. The pronounced association between anhedonia and blunted neural response during loss processing supports a broader concept for the neurobiological basis of anhedonia. Hence, MDD with anhedonic features might be characterized by reduced neural response to external stimuli, potentially because of amotivation., Competing Interests: Competing interests: J. Goltermann received a Society of Biological Psychiatry 2022 travel Award. No other competing interests declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Major depressive disorder (MDD) and type 2 diabetes mellitus (T2D) are known to share clinical comorbidity and to have genetic overlap. Besides their shared genetics, both diseases seem to be associated with alterations in brain structural connectivity and impaired cognitive performance, but little is known about the mechanisms by which genetic risk of T2D might affect brain structure and function and if they do, how these effects could contribute to the disease course of MDD., Methods: This study explores the association of polygenic risk for T2D with structural brain connectome topology and cognitive performance in 434 nondiabetic patients with MDD and 539 healthy control subjects., Results: Polygenic risk score for T2D across MDD patients and healthy control subjects was found to be associated with reduced global fractional anisotropy, a marker of white matter microstructure, an effect found to be predominantly present in MDD-related fronto-temporo-parietal connections. A mediation analysis further suggests that this fractional anisotropy variation may mediate the association between polygenic risk score and cognitive performance., Conclusions: Our findings provide preliminary evidence of a polygenic risk for T2D to be linked to brain structural connectivity and cognition in patients with MDD and healthy control subjects, even in the absence of a direct T2D diagnosis. This suggests an effect of T2D genetic risk on white matter integrity, which may mediate an association of genetic risk for diabetes and cognitive impairments., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Strategies for early detection of prostate cancer aim to detect clinically significant prostate cancer (csPCa) and avoid detection of insignificant cancers and unnecessary biopsies. Swedish national guidelines (SNGs), years 2019 and 2020, involve prostate-specific antigen (PSA) testing, clinical variables, and magnetic resonance imaging (MRI). The Stockholm3 test and MRI have been suggested to improve selection of men for prostate biopsy. Performance of SNGs compared with the Stockholm3 test or MRI in a screening setting is unclear., Objective: To compare strategies based on previous and current national guidelines, Stockholm3, and MRI to select patients for biopsy in a screening-by-invitation setting., Design Setting and Participants: All participants underwent PSA test, and men with PSA ≥3 ng/ml underwent Stockholm3 testing and MRI. Men with Stockholm3 ≥11%, Prostate Imaging Reporting and Data System score ≥3 on MRI, or indication according to SNG-2019 or SNG-2020 were referred to biopsy., Outcome Measurements and Statistical Analysis: The primary outcome was the detection of csPCa at prostate biopsy, defined as an International Society of Urological Pathology (ISUP) grade of ≥2., Results and Limitations: We invited 8764 men from the general population, 272 of whom had PSA ≥3 ng/ml. The median PSA was 4.1 (interquartile range: 3.4-5.8), and 136 of 270 (50%) who underwent MRI lacked any pathological lesions. In total, 37 csPCa cases were diagnosed. Using SNG-2019, 36 csPCa cases with a high biopsy rate (179 of 272) were detected and 49 were diagnosed with ISUP 1 cancers. The Stockholm3 strategy diagnosed 32 csPCa cases, with 89 biopsied and 27 ISUP 1 cancers. SNG-2020 detected 32 csPCa and 33 ISUP 1 cancer patients, with 99 men biopsied, and the MRI strategy detected 30 csPCa and 35 ISUP 1 cancer cases by biopsying 123 men. The latter two strategies generated more MRI scans than the Stockholm3 strategy ( n = 270 vs 33)., Conclusions: Previous guidelines provide high detection of significant cancer but at high biopsy rates and detection of insignificant cancer. The Stockholm3 test may improve diagnostic precision compared with the current guidelines or using only MRI., Patient Summary: The Stockholm3 test facilitates detection of significant cancer, and reduces the number of biopsies and detection of insignificant cancer., (© 2022 The Author(s).)

Acute symptomatic seizures occurring in close temporal relationship with an acute CNS insult are distinct from epilepsy and occur frequently in clinical practice. The aim of this educational review is to provide information on the most important aspects related to acute symptomatic seizures that will allow clinicians to accurately distinguish acute symptomatic seizures from epilepsy in their patients. We explain the definition of acute symptomatic seizures and we illustrate how acute symptomatic seizures differ from epilepsy. We describe acute symptomatic seizures in the context of their various underlying aetiologies and we discuss the approach to the management of patients with acute symptomatic seizures.

The regional variability in tundra and boreal carbon dioxide (CO 2 ) fluxes can be high, complicating efforts to quantify sink-source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO 2 fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been assessed in detail. Here, we compile eddy covariance and chamber measurements of annual and growing season CO 2 fluxes of gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem exchange (NEE) during 1990-2015 from 148 terrestrial high-latitude (i.e., tundra and boreal) sites to analyze the spatial patterns and drivers of CO 2 fluxes and test the accuracy and uncertainty of different statistical models. CO 2 fluxes were upscaled at relatively high spatial resolution (1 km 2 ) across the high-latitude region using five commonly used statistical models and their ensemble, that is, the median of all five models, using climatic, vegetation, and soil predictors. We found the performance of machine learning and ensemble predictions to outperform traditional regression methods. We also found the predictive performance of NEE-focused models to be low, relative to models predicting GPP and ER. Our data compilation and ensemble predictions showed that CO 2 sink strength was larger in the boreal biome (observed and predicted average annual NEE -46 and -29 g C m -2  yr -1 , respectively) compared to tundra (average annual NEE +10 and -2 g C m -2  yr -1 ). This pattern was associated with large spatial variability, reflecting local heterogeneity in soil organic carbon stocks, climate, and vegetation productivity. The terrestrial ecosystem CO 2 budget, estimated using the annual NEE ensemble prediction, suggests the high-latitude region was on average an annual CO 2 sink during 1990-2015, although uncertainty remains high., (© 2021 John Wiley & Sons Ltd.)

Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra.

Several emergencies were admitted less frequently to the hospital during the coronavirus disease 2019 (COVID-19) pandemic. To investigate whether this also occurred with status epilepticus (SE) we compared admissions due to first SE from March to April 2020 ("Time of COVID," TOC) with January to February 2020 ("pre-COVID," preCOV). We also compared admission numbers in TOC and preCOV with the respective 2-month periods in 2018 and 2019 in a retrospective cohort analysis. Two investigators independently searched the hospital patient database for various forms of SE. There was no significant change in the 2-month incidences of first SE in the city of Salzburg from preCOV of 6.1 (95% confidence interval [CI] 2.9-12.3) to TOC of 6.9/100 000 adults (95% CI 3.4-13.3). Admission numbers did not differ significantly from previous years. Estimated adjusted incidence was in line with a recent 5-year epidemiological study in Salzburg. However, a trend toward less-frequent nonconvulsive SE (NCSE) and loss of female predominance were indirect hints of underdiagnosing SE. In contrast to other medical conditions, SE most often presents clinically with impaired consciousness, which may promote admission to emergency departments even in times of lock-down. Further research of medical support of women and patients with NCSE during pandemic-related restrictions is warranted., (© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Globally, soils store two to three times as much carbon as currently resides in the atmosphere, and it is critical to understand how soil greenhouse gas (GHG) emissions and uptake will respond to ongoing climate change. In particular, the soil-to-atmosphere CO 2 flux, commonly though imprecisely termed soil respiration (R S ), is one of the largest carbon fluxes in the Earth system. An increasing number of high-frequency R S measurements (typically, from an automated system with hourly sampling) have been made over the last two decades; an increasing number of methane measurements are being made with such systems as well. Such high frequency data are an invaluable resource for understanding GHG fluxes, but lack a central database or repository. Here we describe the lightweight, open-source COSORE (COntinuous SOil REspiration) database and software, that focuses on automated, continuous and long-term GHG flux datasets, and is intended to serve as a community resource for earth sciences, climate change syntheses and model evaluation. Contributed datasets are mapped to a single, consistent standard, with metadata on contributors, geographic location, measurement conditions and ancillary data. The design emphasizes the importance of reproducibility, scientific transparency and open access to data. While being oriented towards continuously measured R S , the database design accommodates other soil-atmosphere measurements (e.g. ecosystem respiration, chamber-measured net ecosystem exchange, methane fluxes) as well as experimental treatments (heterotrophic only, etc.). We give brief examples of the types of analyses possible using this new community resource and describe its accompanying R software package., (© 2020 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

The rapid conversion of native forests to farmland in Ethiopia, the cradle of biodiversity, threatens the diversity of the arbuscular mycorrhizal fungi (AMF) pivotal to plant nutrition and carbon sequestration. This study aimed to investigate the impact of this land-use change on the AMF species composition and diversity in southern Ethiopia. Soil samples were collected from nine plots in each of three land-use types: native forest, agroforestry, and khat monocropping. The plots of the three land-use types were located adjacent to each other for each of the nine replicates. Three 10 × 10m subplots per plot were sampled. AMF spores were extracted from the soil samples, spore densities were determined, and species composition and diversity were evaluated through morphological analysis. Both spore density and species richness were statistically significantly higher in the native forest than in the agroforestry plots with no clear difference to khat, whereas the true diversity (exponential of Shannon-Wiener diversity index) did not differ among the three land-use types due to high evenness among the species in agroforestry. In total, 37 AMF morphotypes belonging to 12 genera in Glomeromycota were found, dominated by members of the genera Acaulospora and Glomus. The highest isolation frequency index (78%) was recorded for Acaulospora koskei from native forest. Consequently, the agroforestry system did not appear to aid in preserving the AMF species richness of native forests relative to perennial monocropping, such as khat cultivation. In contrast, the native forest areas can serve as in situ genetic reserves of mycorrhizal symbionts adapted to the local vegetative, edaphic, and microbial conditions.

Human impact is rapidly changing vegetation globally. The effect of plant cover that no longer exists in a site may still affect the development of future vegetation. We focused on a little studied factor-arbuscular mycorrhizal (AM) fungus spore bank-and its effect on three test plant species. In a low Arctic field site, plots were maintained for 6 years, devoid of any vegetation or with a Solidago virgaurea monoculture cover. We analysed the AM fungal morphospecies composition and identified 21 morphospecies in the field plots. The AM morphospecies community was dominated by members of Acaulosporaceae. Monoculturing under low Arctic field conditions changed the soil AM spore community, which became dominated by Glomus hoi. We tested the soil feedback in the greenhouse and grew Solidago virgaurea, Potentilla crantzii and Anthoxanthum odoratum in the field soils from the plots without plant cover, covered with Solidago virgaurea or with intact vegetation. Our results suggest that monoculturing resulted in improved N acquisition by the monocultured plant species Solidago virgaurea which may be related to the AM fungus community. Our results show that a rich community of AM fungus spores may remain viable under field conditions for 6 years in the low Arctic. Spore longevity in field soil in the absence of any host plants differed among AM fungus species. We suggest that AM fungus spore longevity be considered an AM fungal life-history trait.

Major depressive disorder (MDD) is associated to affected brain wiring. Little is known whether these changes are stable over time and hence might represent a biological predisposition, or whether these are state markers of current disease severity and recovery after a depressive episode. Human white matter network ("connectome") analysis via network science is a suitable tool to investigate the association between affected brain connectivity and MDD. This study examines structural connectome topology in 464 MDD patients (mean age: 36.6 years) and 432 healthy controls (35.6 years). MDD patients were stratified categorially by current disease status (acute vs. partial remission vs. full remission) based on DSM-IV criteria. Current symptom severity was assessed continuously via the Hamilton Depression Rating Scale (HAMD). Connectome matrices were created via a combination of T1-weighted magnetic resonance imaging (MRI) and tractography methods based on diffusion-weighted imaging. Global tract-based metrics were not found to show significant differences between disease status groups, suggesting conserved global brain connectivity in MDD. In contrast, reduced global fractional anisotropy (FA) was observed specifically in acute depressed patients compared to fully remitted patients and healthy controls. Within the MDD patients, FA in a subnetwork including frontal, temporal, insular, and parietal nodes was negatively associated with HAMD, an effect remaining when correcting for lifetime disease severity. Therefore, our findings provide new evidence of MDD to be associated with structural, yet dynamic, state-dependent connectome alterations, which covary with current disease severity and remission status after a depressive episode.

Glutamate dehydrogenase (NAD(H)- GDH, EC 1.4.1.2) is an important enzyme in nitrogen (N) metabolism. It serves as a link between C and N metabolism, in its role of assimilating ammonia into glutamine or deaminating glutamate into 2-oxoglutarate and ammonia. GDH may also have a key in the N assimilation of legumes growing in P-poor soils. Virgilia divaricata is such a legume, growing in the nutrient limited soils of the mediterranean-type Cape fynbos ecosystem. In order to understand the role of GDH in the nitrogen nutrition of V. divaricata, the aim of this study was to identify the GDH gene transcripts, their relative expressions and enzyme activity in P-stressed roots and nodules during N metabolism. During P deficiency there was a reduction in total plant biomass as well as total plant P concentration. The analysis of the GDH cDNA sequences in V. divaricata revealed the presence of GHD1 and GHD2 subunits, these corresponding to the GDH1, GDH-B and GDH3 genes of legumes and non-legume plants. The relative expression of GDH1 and GDH2 genes in the roots and nodules, indicates that two the subunits were differently regulated depending on the organ type, rather than P supply. Although both transcripts appeared to be ubiquitously expressed in the roots and nodules, the GDH2 transcript evidently predominated over those of GDH1. Furthermore, the higher expression of both GDH transcripts in the roots than nodules, suggests that roots are more reliant on on GDH in P-poor soils, than nodules. With regards to GHD activity, both aminating and deaminating GDH activities were differently affected by P deficiency in roots and nodules. This may function to assimilate N and regulate internal C and N in the roots and nodules. The variation in GDH1 and GDH2 transcript expression and GDH enzyme activities, indicate that the enzyme may be regulated by post-translational modification, instead of by gene expression during P deficiency in V. divaricata., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Heavy metals may adversely affect health in marine organisms. As top predators, sharks may be especially vulnerable to exposure over long lifespans. Here we evaluate plasma levels of 14 heavy metals and 12 trace elements in white sharks, Carcharodon carcharias, in South Africa to determine whether they are related to sex, body size, and/or body condition and other health parameters. High levels of mercury and arsenic were found in shark blood at levels considered toxic in other vertebrates. Heavy metal concentrations were not related to body size or sex. Metal concentrations were not related to body condition with exception of copper, which was positively correlated. Protective effects of elements such as selenium, zinc, and iron were not detected. No negative effects on health parameters, such as total leukocytes or granulocyte to lymphocyte ratios were observed. Results suggest that sharks may have protective mechanisms that mitigate harmful effects of heavy metal exposure, providing new opportunities for future studies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In the version of this Article originally published, the following sentence was missing from the Acknowledgements: "This work was supported by the Norwegian Research Council SnoEco project, grant number 230970". This text has now been added.

Background: A rapid digestibility and high leucine content are considered important for maximal stimulation of muscle protein synthesis. Consequently, with these properties, native whey may hold greater anabolic potential than milk, when supplemented in combination with strength training. Our aim was to compare the effects of supplementation with milk or native whey, during a 12-wk strength training period, on gains in muscle mass and strength in young adults., Methods: In this double-blinded, randomized, controlled study a total of 40 untrained young men and women received two daily servings of either milk or native whey containing 20 g of protein, during a 12-wk strength training intervention. Muscle strength, lean mass, thigh muscle cross-sectional area, m. vastus lateralis thickness and muscle fiber cross-sectional area were assessed before and after the training period. In addition, the acute phosphorylation of the anabolic kinases p70S6K, 4E-BP1 and eEF-2 in response to a standardized workout and supplementation was investigated before and after the 12-wk training period., Results: Muscle mass and strength increased, by all measures applied (5%-16%, P < 0.001), with no differences between groups (P > 0.25). p70S6K phosphorylation increased (~1000%, P < 0.02) 2 h after exercise in the untrained and trained state, but no differences in anabolic signaling were observed between supplements (P > 0.40). No correlation between these acute measures and changes in muscle mass or strength were observed., Conclusion: Supplementation with milk or native whey during a 12-wk strength training period did not differentially affect muscle mass and strength in young untrained individuals.

Advancing phenology is one of the most visible effects of climate change on plant communities, and has been especially pronounced in temperature-limited tundra ecosystems. However, phenological responses have been shown to differ greatly between species, with some species shifting phenology more than others. We analysed a database of 42,689 tundra plant phenological observations to show that warmer temperatures are leading to a contraction of community-level flowering seasons in tundra ecosystems due to a greater advancement in the flowering times of late-flowering species than early-flowering species. Shorter flowering seasons with a changing climate have the potential to alter trophic interactions in tundra ecosystems. Interestingly, these findings differ from those of warmer ecosystems, where early-flowering species have been found to be more sensitive to temperature change, suggesting that community-level phenological responses to warming can vary greatly between biomes.

Climate warming can result in both abiotic (e.g., permafrost thaw) and biotic (e.g., microbial functional genes) changes in Arctic tundra. Recent research has incorporated dynamic permafrost thaw in Earth system models (ESMs) and indicates that Arctic tundra could be a significant future carbon (C) source due to the enhanced decomposition of thawed deep soil C. However, warming-induced biotic changes may influence biologically related parameters and the consequent projections in ESMs. How model parameters associated with biotic responses will change under warming and to what extent these changes affect projected C budgets have not been carefully examined. In this study, we synthesized six data sets over 5 years from a soil warming experiment at the Eight Mile Lake, Alaska, into the Terrestrial ECOsystem (TECO) model with a probabilistic inversion approach. The TECO model used multiple soil layers to track dynamics of thawed soil under different treatments. Our results show that warming increased light use efficiency of vegetation photosynthesis but decreased baseline (i.e., environment-corrected) turnover rates of SOC in both the fast and slow pools in comparison with those under control. Moreover, the parameter changes generally amplified over time, suggesting processes of gradual physiological acclimation and functional gene shifts of both plants and microbes. The TECO model predicted that field warming from 2009 to 2013 resulted in cumulative C losses of 224 or 87 g/m 2 , respectively, without or with changes in those parameters. Thus, warming-induced parameter changes reduced predicted soil C loss by 61%. Our study suggests that it is critical to incorporate biotic changes in ESMs to improve the model performance in predicting C dynamics in permafrost regions., (© 2018 John Wiley & Sons Ltd.)

Objective: This study evaluated the outcome with a treatment strategy for high-risk prostate cancer (PCa) using extended pelvic lymph-node dissection (eLND) followed by external beam radiation therapy (EBRT) in lymph-node-positive (LNpos) and lymph-node-negative (LNneg) cases compared with the strategy with limited pelvic lymph-node dissection (lLND) and only giving EBRT to LNneg cases., Materials and Methods: From 2000 to 2006, 124 men with high-risk PCa underwent lLND and initiated androgen deprivation therapy (ADT) before planned EBRT. LNpos patients were excluded from EBRT following the SPCG-7 study strategy (group I). From 2007 to 2013, 111 patients underwent eLND and started ADT before EBRT, and LNneg and most LNpos patients received EBRT (group II). Using Kaplan-Meier plots and multivariable Cox regression, biochemical recurrence-free, metastasis-free, cancer-specific survival and overall survival were compared during a 10 year follow-up., Results: PSA progression-free survival rates after 2, 4, 6, 8 and 10 years were 78%, 66%, 52%, 45% and 41% in group I, and 88%, 83%, 78%, 69% and 69% in group II (p < 0.001), respectively. Group II had a lower risk of PSA progression [hazard ratio (HR) = 0.43, 95% confidence interval (CI) 0.27,0.69, p = 0.001], metastasis development (HR = 0.51, 95% CI 0.27,0.97, p = 0.040) and overall mortality (HR = 0.49, 95% CI 0.26,0.92, p = 0.027), but not of PCa-specific death (HR = 0.45, 95% CI 0.19,1.08, p = 0.074)., Conclusion: A treatment strategy for high-risk PCa with eLND combined with EBRT in LNneg and LNpos cases may improve outcome compared to a strategy with lLND and offering EBRT only to LNneg cases but ADT to LNpos cases.

Background: The aim of the study was to examine the value of quantitative and qualitative MRI and 11 C acetate PET/CT parameters in predicting regional lymph node (LN) metastasis of newly diagnosed prostate cancer (PCa)., Patients and Methods: Patients with intermediate (n = 6) and high risk (n = 47) PCa underwent 3T MRI (40 patients) and 11 C acetate PET/CT (53 patients) before extended pelvic LN dissection. For each patient the visually most suspicious LN was assessed for mean apparent diffusion coefficient (ADCmean), maximal standardized uptake value (SUVmax), size and shape and the primary tumour for T stage on MRI and ADCmean and SUVmax in the index lesion. The variables were analysed in simple and multiple logistic regression analysis., Results: All variables, except ADCmean and SUVmax of the primary tumor, were independent predictors of LN metastasis. In multiple logistic regression analysis the best model was ADCmean in combintion with MRI T-stage where both were independent predictors of LN metastasis, this combination had an AUC of 0.81 which was higher than the AUC of 0.65 for LN ADCmean alone and the AUC of 0.69 for MRI T-stage alone., Conclusions: Several quantitative and qualitative imaging parameters are predictive of regional LN metastasis in PCa. The combination of ADCmean in lymph nodes and T-stage on MRI was the best model in multiple logistic regression with increased predictive value compared to lymph node ADCmean and T-stage on MRI alone., Competing Interests: Disclosure: Joel Kullberg and Håkan Ahlström are two of the founders of and employed by Antaros Medical AB. This company has not been involved in the presented study

Rapid Arctic warming is expected to increase global greenhouse gas concentrations as permafrost thaw exposes immense stores of frozen carbon (C) to microbial decomposition. Permafrost thaw also stimulates plant growth, which could offset C loss. Using data from 7 years of experimental Air and Soil warming in moist acidic tundra, we show that Soil warming had a much stronger effect on CO 2 flux than Air warming. Soil warming caused rapid permafrost thaw and increased ecosystem respiration (R eco ), gross primary productivity (GPP), and net summer CO 2 storage (NEE). Over 7 years R eco , GPP, and NEE also increased in Control (i.e., ambient plots), but this change could be explained by slow thaw in Control areas. In the initial stages of thaw, R eco , GPP, and NEE increased linearly with thaw across all treatments, despite different rates of thaw. As thaw in Soil warming continued to increase linearly, ground surface subsidence created saturated microsites and suppressed R eco , GPP, and NEE. However R eco and GPP remained high in areas with large Eriophorum vaginatum biomass. In general NEE increased with thaw, but was more strongly correlated with plant biomass than thaw, indicating that higher R eco in deeply thawed areas during summer months was balanced by GPP. Summer CO 2 flux across treatments fit a single quadratic relationship that captured the functional response of CO 2 flux to thaw, water table depth, and plant biomass. These results demonstrate the importance of indirect thaw effects on CO 2 flux: plant growth and water table dynamics. Nonsummer R eco models estimated that the area was an annual CO 2 source during all years of observation. Nonsummer CO 2 loss in warmer, more deeply thawed soils exceeded the increases in summer GPP, and thawed tundra was a net annual CO 2 source., (© 2017 John Wiley & Sons Ltd.)

Warmer temperatures are accelerating the phenology of organisms around the world. Temperature sensitivity of phenology might be greater in colder, higher latitude sites than in warmer regions, in part because small changes in temperature constitute greater relative changes in thermal balance at colder sites. To test this hypothesis, we examined up to 20 years of phenology data for 47 tundra plant species at 18 high-latitude sites along a climatic gradient. Across all species, the timing of leaf emergence and flowering was more sensitive to a given increase in summer temperature at colder than warmer high-latitude locations. A similar pattern was seen over time for the flowering phenology of a widespread species, Cassiope tetragona. These are among the first results highlighting differential phenological responses of plants across a climatic gradient and suggest the possibility of convergence in flowering times and therefore an increase in gene flow across latitudes as the climate warms., (© 2017 John Wiley & Sons Ltd.)

Currently, it has not been satisfactorily established, whether modern low-osmolality iodinated contrast agents (ICAs) used in computed tomography (CT) studies are a risk factor for exacerbation of myasthenic symptoms. The rate of acute adverse events as well as delayed clinical worsening up to 30 days were analyzed in 73 patients with confirmed myasthenia gravis (MG) who underwent contrast-enhanced CT studies and compared to 52 patients who underwent unenhanced CT studies. One acute adverse event was documented. 12.3% of MG patients experienced a delayed exacerbation of symptoms after ICA administration. The rate of delayed severe exacerbation was higher in the contrast-enhanced group. Alternative causes for the exacerbation of MG-related symptoms were more likely than ICA administration in all cases. ICA administration for CT studies in MG patients should not be withheld if indicated, but patients particularly those with concomitant acute diseases should be carefully monitored for exacerbation of symptoms.

In this work we report the stereo-dependent collision-induced dissociation (CID) of proton-bound complexes of tryptophan and 2-butanol. The dissociation efficiency was measured as a function of collision energy in single collision mode. The homochiral complex was found to be less stable against CID than a heterochiral one. Additional gas dependence measurements were performed with diastereomeric complexes that confirm the findings., (© 2017 The Authors. Chirality Published by Wiley Periodicals, Inc.)

Two distinct Phytophthora taxa were found to be associated with brown rot of pomelo (Citrus grandis), a new disease of this ancestral Citrus species, in the Vinh Long province, Mekong River Delta area, southern Vietnam. On the basis of morphological characters and using the ITS1-5.8S-ITS2 region of the rDNA and the cytochrome oxidase subunit 1 (COI) as barcode genes, one of the two taxa was provisionally named as Phytophthora sp. prodigiosa, being closely related to but distinct from P. insolita, a species in Phytophthora Clade 9, while the other one, was closely related to but distinct from the Clade 2 species P. meadii and was informally designated as Phytophthora sp. mekongensis. Isolates of P. sp. prodigiosa and P. sp. mekongensis were also obtained from necrotic fibrous roots of Volkamer lemon (C. volkameriana) rootstocks grafted with 'King' mandarin (Citrus nobilis) and from trees of pomelo, respectively, in other provinces of the Mekong River Delta, indicating a widespread occurrence of both Phytophthora species in this citrus-growing area. Koch's postulates were fulfilled via pathogenicity tests on fruits of various Citrus species, including pomelo, grapefruit (Citrus x paradisi), sweet orange (Citrus x sinensis) and bergamot (Citrus x bergamia) as well as on the rootstock of 2-year-old trees of pomelo and sweet orange on 'Carrizo' citrange (C. sinensis 'Washington Navel' x Poncirus trifoliata). This is the first report of a Phytophthora species from Clade 2 other than P. citricola and P. citrophthora as causal agent of fruit brown rot of Citrus worldwide and the first report of P. insolita complex in Vietnam. Results indicate that likely Vietnam is still an unexplored reservoir of Phytophthora diversity.

Objectives: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine., Patients and Methods: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions., Results: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data., Conclusion: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Perennially frozen soil in high latitude ecosystems (permafrost) currently stores 1330-1580 Pg of carbon (C). As these ecosystems warm, the thaw and decomposition of permafrost is expected to release large amounts of C to the atmosphere. Fortunately, losses from the permafrost C pool will be partially offset by increased plant productivity. The degree to which plants are able to sequester C, however, will be determined by changing nitrogen (N) availability in these thawing soil profiles. N availability currently limits plant productivity in tundra ecosystems but plant access to N is expected improve as decomposition increases in speed and extends to deeper soil horizons. To evaluate the relationship between permafrost thaw and N availability, we monitored N cycling during 5 years of experimentally induced permafrost thaw at the Carbon in Permafrost Experimental Heating Research (CiPEHR) project. Inorganic N availability increased significantly in response to deeper thaw and greater soil moisture induced by Soil warming. This treatment also prompted a 23% increase in aboveground biomass and a 49% increase in foliar N pools. The sedge Eriophorum vaginatum responded most strongly to warming: this species explained 91% of the change in aboveground biomass during the 5 year period. Air warming had little impact when applied alone, but when applied in combination with Soil warming, growing season soil inorganic N availability was significantly reduced. These results demonstrate that there is a strong positive relationship between the depth of permafrost thaw and N availability in tundra ecosystems but that this relationship can be diminished by interactions between increased thaw, warmer air temperatures, and higher levels of soil moisture. Within 5 years of permafrost thaw, plants actively incorporate newly available N into biomass but C storage in live vascular plant biomass is unlikely to be greater than losses from deep soil C pools., (© 2015 John Wiley & Sons Ltd.)

Organic matter (OM) plays a major role in both terrestrial and oceanic biogeochemical cycles. The amount of carbon stored in these systems is far greater than that of carbon dioxide (CO2 ) in the atmosphere, and annual fluxes of CO2 from these pools to the atmosphere exceed those from fossil fuel combustion. Understanding the processes that determine the fate of detrital material is important for predicting the effects that climate change will have on feedbacks to the global carbon cycle. However, Earth System Models (ESMs) typically utilize very simple formulations of processes affecting the mineralization and storage of detrital OM. Recent changes in our view of the nature of this material and the factors controlling its transformation have yet to find their way into models. In this review, we highlight the current understanding of the role and cycling of detrital OM in terrestrial and marine systems and examine how this pool of material is represented in ESMs. We include a discussion of the different mineralization pathways available as organic matter moves from soils, through inland waters to coastal systems and ultimately into open ocean environments. We argue that there is strong commonality between aspects of OM transformation in both terrestrial and marine systems and that our respective scientific communities would benefit from closer collaboration., (© 2015 John Wiley & Sons Ltd.)

Estrogens, via induction of their specific receptors (e.g., ER-α), regulate cell proliferation, differentiation and morphogenesis in mammary epithelium. Cell-cycle progression is driven by activation of complexes consisting of cyclin-dependent kinases (CDKs) and cyclins, which also modulate the activity of ER-α. Loss of control over the cell-cycle results in accelerated cell division and malignant transformation. Thus, a reciprocal relation exists between estrogen signaling and cell proliferation. Based on these findings, a new concept was developed to reduce ER-α activity and bring the cell cycle in transformed cells to heel. Prevention of ER-α activation and control over the deregulated cell cycle was achieved by supplementation with pharmacological CDK inhibitors alone or in combination with selective antiestrogens.

BRCA1/2-mutant cells are hypersensitive to inactivation of poly(ADP-ribose) polymerase 1 (PARP-1). We recently showed that inhibition of PARP-1 by NU1025 is strongly cytotoxic for BRCA1-positive BT-20 cells, but not BRCA1-deficient SKBr-3 cells. These results raised the possibility that other PARP-1 inhibitors, particularly those tested in clinical trials, may be more efficacious against BRCA1-deficient SKBr-3 breast cancer cells than NU1025. Thus, in the presented study the cytotoxicity of four PARP inhibitors under clinical evaluation (olaparib, rucaparib, iniparib and AZD2461) was examined and compared to that of NU1025. The sensitivity of breast cancer cells to the PARP-1 inhibition strongly varied. Remarkably, BRCA-1-deficient SKBr-3 cells were almost completely insensitive to NU1025, olaparib and rucaparib, whereas BRCA1-expressing BT-20 cells were strongly affected by NU1025 even at low doses. In contrast, iniparib and AZD2461 were cytotoxic for both BT-20 and SKBr-3 cells. Of the four tested PARP-1 inhibitors only AZD2461 strongly affected cell cycle progression. Interestingly, the anti-proliferative and pro-apoptotic potential of the tested PARP-1 inhibitors clearly correlated with their capacity to damage DNA. Further analyses revealed that proteomic signatures of the two studied breast cancer cell lines strongly differ, and a set of 197 proteins was differentially expressed in NU1025-treated BT-20 cancer cells. These results indicate that BT-20 cells may harbor an unknown defect in DNA repair pathway(s) rendering them sensitive to PARP-1 inhibition. They also imply that therapeutic applicability of PARP-1 inhibitors is not limited to BRCA mutation carriers but can be extended to patients harboring deficiencies in other components of the pathway(s)., (© 2015 Wiley Periodicals, Inc.)

Arbuscular mycorrhizal fungi (AMF) form probably the most widespread symbiosis on earth and are found across all ecosystems including the Arctic regions. In the Arctic, the prevalent harsh cold conditions experienced by both host plants and fungi may have selected for AMF species with long-surviving spores, the principal means for dispersal and survival. However, basic knowledge about their viability is lacking. AMF spore assembly from two Arctic sites was examined in soil samples collected across an 11-year period and stored at -20 °C for up to 10 years. AMF spore viability and ability to colonize plants were investigated in the greenhouse using Plantago lanceolata. It was predicted that Arctic AMF spores would survive in cold conditions for several years, with an expected decrease in viability over time as suggested by other experiments with temperate material. Results show that even though the two study sites differed in AMF spore density, the relative abundance of spore morphotypes was rather similar across sites and years. Furthermore, spore viability over time was site-dependent as it decreased only in one site. Although spores were viable, only a very small proportion of hosts and roots became colonized in the greenhouse even 21 months after inoculation. Taken together, these results suggest a certain site-dependent variability in AMF spore communities and the ability of Arctic AMF spores to remain viable after a long-term storage in cold conditions. The lack of host colonization in the greenhouse may be related to the inability to overcome spore dormancy under these conditions.

Importance: Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity., Objective: To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management., Design, Setting, and Participants: Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated., Interventions: In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis)., Main Outcomes and Measures: Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting., Results: Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation., Conclusions and Relevance: Rates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon. We recommend establishing the patient's VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.

It is not known how phosphate (P) deficiency affects the allocation of carbon (C) to biological nitrogen fixation (BNF) in legumes. The alteration of the respiratory and photosynthetic C costs of BNF was investigated under P deficiency. Although BNF can impose considerable sink stimulation on host respiratory and photosynthetic C, it is not known how the change in the C and energy allocation during P deficiency may affect BNF. Nodulated Lupinus luteus plants were grown in sand culture, using a modified Long Ashton nutrient solution containing no nitrogen (N) for ca. four weeks, after which one set was exposed to a P-deficient nutrient medium, while the other set continued growing on a P-sufficient nutrient medium. Phosphorus stress was measured at 20 days after onset of P-starvation. During P stress the decline in nodular P levels was associated with lower BNF and nodule growth. There was also a shift in the balance of photosynthetic and respiratory C toward a loss of C during P stress. Below-ground respiration declined under limiting P conditions. However, during this decline there was also a shift in the proportion of respiratory energy from maintenance toward growth respiration. Under P stress, there was an increased allocation of C toward root growth, thereby decreasing the amount of C available for maintenance respiration. It is therefore possible that the decline in BNF under P deficiency may be due to this change in resource allocation away from respiration associated with direct nutrient uptake, but rather toward a long term nutrient acquisition strategy of increased root growth., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: Incontinence is a drawback after radical prostatectomy for prostate cancer. Several surgical methods to improve continence have been described however with contradictory results., Objective: To determine whether a modified surgical technique during laparoscopic radical prostatectomy (LRP) improves postoperative continence., Patients and Methods: This is a prospective nonrandomized study with two consecutive series of 100 patients in each group. The first group from 2005 to 2008 underwent a standard LRP. The second group from 2009 to 2011 was subjected to a modified LRP by sparing of puboprostatic ligaments, including the preservation of arcus tendineous, and using a simple posterior tension-releasing suture adapting the urethra stump to the bladder before the anastomosis. The patients had the same preoperative work-up and comparable preoperative baseline characteristics. The 2-year follow-up of the patients included a continence questionnaire and International Prostate Symptom Score (IPSS). Urinary peak flow (Qmax) and post-void residual (PVR) volume were assessed at 3 months. Continence was defined as 0-1 pad/day., Results: Only 99 patients were evaluated in each group. The patients had comparable operative characteristics. The continence rates after the modified technique vs the standard were 33% vs 16%, p=0.007 at 1 month; 66% vs 44%, p=0.002 at 3 months; 81% vs 67%, p=0.034 at 6 months; 92% vs 80%, p=0.024 at 12 months; and 95% vs 86%, p=0.05 at 2 years. No significant differences were found regarding voiding functions, the Qmax, the PVR volume, or the IPSS. Three patients developed urethral stricture in the standard group compared with none in the modified group. The negative margin rates were unchanged., Conclusions: The anterior preservation and posterior suture technique studied is a simple, safe, and efficient method to shorten the time to continence after LRP without adverse effects on voiding or compromising the margin rates.

We study the nonequilibrium dynamics of correlations in quantum lattice models in the presence of long-range interactions decaying asymptotically as a power law. For exponents larger than the lattice dimensionality, a Lieb-Robinson-type bound effectively restricts the spreading of correlations to a causal region, but allows supersonic propagation. We show that this decay is not only sufficient but also necessary. Using tools of quantum metrology, for any exponents smaller than the lattice dimension, we construct Hamiltonians giving rise to quantum channels with capacities not restricted to a causal region. An analytical analysis of long-range Ising models illustrates the disappearance of the causal region and the creation of correlations becoming distance independent. Numerical results obtained using matrix product state methods for the XXZ spin chain reveal the presence of a sound cone for large exponents and supersonic propagation for small ones. In all models we analyzed, the fast spreading of correlations follows a power law, but not the exponential increase of the long-range Lieb-Robinson bound.

Parapharyngodon grenadaensis n. sp. (Nematoda: Pharyngodonidae) from the large intestine of the cane toad, Rhinella marina, is described and illustrated. Parapharyngodon grenadaensis n. sp. is the 48th species assigned to the genus and the 16th species from the Neotropical region. It differs from other species in the genus by possessing 4 pairs of caudal papillae, an echinate anterior cloacal lip, and a blunt spicule of 67-104 μm. This is only the second report of R. marina harboring a species of Parapharyngodon.

As part of the endangered humpback chub (HBC; Gila cypha ) Adaptive Management Program, a parasite survey was conducted from 28 June to 17 July 2006 in 8 tributaries and 7 adjacent sections of the main stem of the Colorado River, U.S.A. In total, 717 fish were caught, including 24 HBC. Field necropsies yielded 19 parasite species, 5 of which (Achtheres sp., Kathlaniidae gen. sp., Caryophyllaidae gen. sp., Myxidium sp., and Octomacrum sp.) are new records for Grand Canyon, Arizona, U.S.A. Spearman's correlation coefficient analyses showed no correlations between parasite burden and fork length for various combinations of fish and parasite species. Regression analyses suggest that no parasite species had a strong effect on fish length. The most diverse parasite community (n = 14) was at river kilometer (Rkm) 230, near the confluence of Kanab Creek. The most diverse parasite infracommunity (n = 12) was found in the non-native channel catfish (CCF; Ictaluris punctatus). Overall parasite prevalence was highest in CCF (85%) followed by that in HBC (58%). The parasite fauna of humpback chub was mainly composed of Bothriocephalus acheilognathi and Ornithodiplostomum sp. metacercariae.

The aim of this work was to study the effect of long-term contrasting cropping systems on the indigenous arbuscular mycorrhizal fungal (AMF) spore populations in the soil of a field experiment located in western Finland. Conventional and low-input cropping systems were compared, each with two nutrient management regimes. The conventional cropping system with a non-leguminous 6-year crop rotation (barley-barley-rye-oat-potato-oat) was fertilized at either full (rotation A) or half (rotation B) the recommended rate. In the low-input cropping system, plant residues were returned to the plots either as such (rotation C) or composted (rotation D). In the rotation of this system, 1 year with barley was replaced by clover, and oat was cultivated mixed with pea. Thus, the 6-year rotation was barley-red clover-rye-oat + pea-potato-oat + pea. Each rotation was replicated three times, starting the 6-year rotation in three different years, these being designated point 1, point 2, and point 3, respectively. In the low-input system, biotite and rock phosphate were used to compensate for K and P in the harvested yield, while animal manure was applied at the start only. After 13 years, rotation points 1 and 3 were studied. Barley was the standing crop in all plots of rotation point 1, while oat and oat + pea were grown in rotations C and D, respectively. AMF spores were studied by direct extraction and by trapping, sampled on 15 June and 15 August. In addition, a special assay was designed for isolation of fast colonizing, dominating AMF. The cropping system did not significantly affect AMF spore densities, although the low-input cropping system with composted plant residues had the highest density with 44 spores on average and the conventional system with full fertilization 24 spores per 100 cm(3) soil in the autumn samples. Species richness was low in the experimental area. Five Glomus spp., one Acaulospora, and one Scutellospora were identified at the species level. In addition to these, three unidentified Glomus spp. were found. Species richness was not affected by cropping system, rotation point, or their interactions. The Shannon-Wiener index of AMF spore distributions was significantly higher in the fully fertilized than in the half-fertilized conventional plots. Glomus claroideum was the most commonly identified single species in the experimental area. It occurred in all the cropping systems and their various rotation points, representing about 30% of the total number of identified spores. In August, G. claroideum accounted for as much as 45-55% of the total numbers of spores identified in the conventional system with halved fertilization. In contrast, Glomus mosseae occurred more commonly in June (26%) than in August (9%). A bioassay using roots as inoculum for isolation and culture of dominating AMF was successfully developed and yielded only G. claroideum. This indicates a high probability of being able to more generally identify, isolate, and culture fast colonizing generalist AMF for use as inoculants in agriculture and horticulture.