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Ongoing climate change poses an increasing threat to biodiversity. To avoid decline or extinction, species need to either adjust or adapt to new environmental conditions or track their climatic niches across space. In sessile organisms such as plants, phenotypic plasticity can help maintain fitness in variable and even novel environmental conditions and is therefore likely to play an important role in allowing them to survive climate change, particularly in the short term. Understanding a species' response to rising temperature is crucial for planning well-targeted and cost-effective conservation measures. We sampled seeds of three Hypericum species ( H. maculatum , H. montanum , and H. perforatum ), from a total of 23 populations originating from different parts of their native distribution areas in Europe. We grew them under four different temperature regimes in a greenhouse to simulate current and predicted future climatic conditions in the distribution areas. We measured flowering start, flower count, and subsequent seed weight, allowing us to study variations in the thermal plasticity of flowering phenology and its relation to fitness. Our results show that individuals flowered earlier with increasing temperature, while the degree of phenological plasticity varied among species. More specifically, the plasticity of H. maculatum varied depending on population origin, with individuals from the leading range edge being less plastic. Importantly, we show a positive relationship between higher plasticity and increased flower production, indicating adaptive phenological plasticity. The observed connection between plasticity and fitness supports the idea that plasticity may be adaptive. This study underlines the need for information on plasticity for predicting species' potential to thrive under global change and the need for studies on whether higher phenotypic plasticity is currently being selected as natural populations experience a rapidly changing climate., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Spontaneous rhythmic movements are part of everyday life, e.g., in walking, clapping or music making. Humans perform such spontaneous motor actions at different rates that reflect specific biomechanical constraints of the effector system in use. However, there is some evidence for intra-individual consistency of specific spontaneous rates arguably resulting from common underlying processes. Additionally, individual and contextual factors such as musicianship and circadian rhythms have been suggested to influence spontaneous rates. This study investigated the relative contributions of these factors and provides a comprehensive picture of rates among different spontaneous motor behaviors, i.e., melody production, walking, clapping, tapping with and without sound production, the latter measured online before and in the lab. Participants (n = 60) exhibited high intra-individual stability across tasks. Task-related influences included faster tempi for spontaneous production rates of music and wider ranges of spontaneous motor tempi (SMT) and clapping rates compared to walking and music making rates. Moreover, musicians exhibited slower spontaneous rates across tasks, yet we found no influence of time of day on SMT as measured online in pre-lab sessions. Tapping behavior was similar in pre-lab and in-lab sessions, validating the use of online SMT assessments. Together, the prominent role of individual factors and high stability across domains support the idea that different spontaneous motor behaviors are influenced by common underlying processes., (© 2024. The Author(s).)

In a previous experiment, we found evidence for a bodily hierarchy governing interlimb coordination of rhythm and beat, using five effectors: 1) Left foot, 2) Right foot, 3) Left hand, 4) Right hand and 5) Voice. The hierarchy implies that, during simultaneous rhythm and beat performance and using combinations of two of these effectors, executing the task by performing the rhythm with an effector that has a higher number than the beat effector is significantly easier than vice versa. To investigate the neural underpinnings of this proposed bodily hierarchy, we here scanned 46 professional musicians using fMRI as they performed a rhythmic pattern with one effector while keeping the beat with another. The conditions combined the voice and the right hand (V + RH), the right hand and the left hand (RH + LH), and the left hand and the right foot (LH + RF). Each effector combination was performed with and against the bodily hierarchy. Going against the bodily hierarchy increased tapping errors significantly and also increased activity in key brain areas functionally associated with top-down sensorimotor control and bottom-up feedback processing, such as the cerebellum and SMA. Conversely, going with the bodily hierarchy engaged areas functionally associated with the default mode network and regions involved in emotion processing. Theories of general brain function that hold prediction as a key principle, propose that action and perception are governed by the brain's attempt to minimise prediction error at different levels in the brain. Following this viewpoint, our results indicate that going against the hierarchy induces stronger prediction errors, while going with the hierarchy allows for a higher degree of automatization. Our results also support the notion of a bodily hierarchy in motor control that prioritizes certain conductive and supportive tapping roles in specific effector combinations., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The regulation of microRNA (miRNA) biogenesis is crucial for maintaining plant homeostasis under biotic and abiotic stress. The crosstalk between the RNA polymerase II (Pol-II) complex and the miRNA processing machinery has emerged as a central hub modulating transcription and cotranscriptional processing of primary miRNA transcripts (pri-miRNAs). However, it remains unclear how miRNA-specific transcriptional regulators recognize MIRNA loci. Here, we show that the Arabidopsis (Arabidopsis thaliana) HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15)-HISTONE DEACETYLASE9 (HDA9) complex is a conditional suppressor of miRNA biogenesis, particularly in response to abscisic acid (ABA). When treated with ABA, hos15/hda9 mutants show enhanced transcription of pri-miRNAs that is accompanied by increased processing, leading to overaccumulation of a set of mature miRNAs. Moreover, upon recognition of the nascent pri-miRNAs, the ABA-induced recruitment of the HOS15-HDA9 complex to MIRNA loci is guided by HYPONASTIC LEAVES 1 (HYL1). The HYL1-dependent recruitment of the HOS15-HDA9 complex to MIRNA loci suppresses expression of MIRNAs and processing of pri-miRNA. Most importantly, our findings indicate that nascent pri-miRNAs serve as scaffolds for recruiting transcriptional regulators, specifically to MIRNA loci. This indicates that RNA molecules can act as regulators of their own expression by causing a negative feedback loop that turns off their transcription, providing a self-buffering system., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background and Aims: Climate-change induced warmer spring temperatures advance tree leaf-out and result in earlier shading of the forest floor. Climate change also leads to more frequent droughts. Forest understorey herbs may respond to these environmental changes by varying traits at different hierarchical levels of organization. While trait mean variation at the inter-individual level in response to environmental changes is well-studied, little is known about how variation at the intra-individual level responds., Methods: We sampled genets of the forest understorey herb Galium odoratum from 21 populations in three regions in Germany, varying in microclimatic conditions. The genets were transplanted into a common garden, where we applied shading and drought treatments. We measured plant height and leaf length and width, and calculated the coefficient of variation (CV) at different hierarchical levels: intra-population, intra-genet, intra-ramet and intra-shoot., Key Results: Variance partitioning showed that intra-shoot CV represented most of the total variation, followed by intra-ramet CV. We found significant variation in CV of plant height and leaf width among populations of origin, indicating that CV is at least partly genetically based. The soil temperature at populations' origins correlated negatively with CV in plant height, suggesting adaptation to local conditions. Furthermore, we observed that early shade led to increased intra-ramet CV in leaf length, while drought reduced intra-shoot CV in leaf width. Finally, intra-shoot leaf width mean and CV were independent under control conditions but correlated under drought., Conclusions: Our experimental results reveal correlations of intra-individual variation with soil temperature, indicating that intra-individual variation can evolve and may be adaptive. Intra-individual variation responded plastically to drought and shading, suggesting functional changes to improve light capture and reduce evapotranspiration. In conclusion, intra-individual variation makes up the majority of total trait variation in this species and can play a key role in plant adaptation to climatic change., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Addressable quantum states well isolated from the environment are of considerable interest for quantum information science and technology. Carbon nanotubes are an appealing system, since a perfect crystal can be grown without any missing atoms and its cylindrical structure prevents ill-defined atomic arrangement at the surface. Here, we develop a reliable process to fabricate compact multielectrode circuits that can sustain the harsh conditions of the nanotube growth. Nanotubes are suspended over multiple gate electrodes, which are themselves structured over narrow dielectric ridges to reduce the effect of the charge fluctuators of the substrate. We measure high-quality double- and triple-quantum dot charge stability diagrams. Transport measurements through the triple-quantum dot indicate long-range tunneling of single electrons between the left and right quantum dots. This work paves the way to the realization of a new generation of condensed-matter devices in an ultraclean environment, including spin qubits, mechanical qubits, and quantum simulators.

Little is known about expertise-related plasticity of neural mechanisms for auditory feature integration. Here, we contrast two diverging hypotheses that musical expertise is associated with more independent or more integrated predictive processing of acoustic features relevant to melody perception. Mismatch negativity (MMNm) was recorded with magnetoencephalography (MEG) from 25 musicians and 25 non-musicians, exposed to interleaved blocks of a complex, melody-like multi-feature paradigm and a simple, oddball control paradigm. In addition to single deviants differing in frequency (F), intensity (I), or perceived location (L), double and triple deviants were included reflecting all possible feature combinations (FI, IL, LF, FIL). Following previous work, early neural processing overlap was approximated in terms of MMNm additivity by comparing empirical MMNms obtained with double and triple deviants to modeled MMNms corresponding to summed constituent single-deviant MMNms. Significantly greater subadditivity was found in musicians compared to non-musicians, specifically for frequency-related deviants in complex, melody-like stimuli. Despite using identical sounds, expertise effects were absent from the simple oddball paradigm. This novel finding supports the integrated processing hypothesis whereby musicians recruit overlapping neural resources facilitating more integrative representations of contextually relevant stimuli such as frequency (perceived as pitch) during melody perception. More generally, these specialized refinements in predictive processing may enable experts to optimally capitalize upon complex, domain-relevant, acoustic cues., 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 © 2022 Hansen, Højlund, Møller, Pearce and Vuust.)

Interlimb coordination is critical to the successful performance of simple activities in everyday life and it depends on precisely timed perception-action coupling. This is particularly true in music-making, where performers often use body-movements to keep the beat while playing more complex rhythmic patterns. In the current study, we used a musical rhythmic paradigm of simultaneous rhythm/beat performance to examine how interlimb coordination between voice, hands and feet is influenced by the inherent figure-ground relationship between rhythm and beat. Sixty right-handed participants-professional musicians, amateur musicians and non-musicians-performed three short rhythmic patterns while keeping the underlying beat, using 12 different combinations of voice, hands and feet. Results revealed a bodily hierarchy with five levels (1) left foot, (2) right foot, (3) left hand, (4) right hand, (5) voice, i.e., more precise task execution was observed when the rhythm was performed with an effector occupying a higher level in the hierarchy than the effector keeping the beat. The notion of a bodily hierarchy implies that the role assigned to the different effectors is key to successful interlimb coordination: the performance level of a specific effector combination differs considerably, depending on which effector holds the supporting role of the beat and which effector holds the conducting role of the rhythm. Although performance generally increased with expertise, the evidence of the hierarchy was consistent in all three expertise groups. The effects of expertise further highlight how perception influences action. We discuss the possibility that musicians' more robust metrical prediction models make it easier for musicians to attenuate prediction errors than non-musicians. Overall, the study suggests a comprehensive bodily hierarchy, showing how interlimb coordination is influenced by hierarchical principles in both perception and action., (© 2022. The Author(s).)

The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1 K154A mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Background: Lungs from donation after circulatory death (DCD) may be an underused resource for transplantation. The aim was to investigate, with a DCD pig model, if it was possible to recondition lungs exposed for up to 2 h of warm ischaemia with ex vivo lung perfusion (EVLP)., Methods: Danish domestic pigs (N = 17) were randomized into three groups. In the two study groups, lungs were exposed to either 1 or 2 h of warm ischaemia. All lungs were reconditioned and evaluated after 83 ± 38 minutes of perfusion at FiO2 1.0 and 0.21 with EVLP. Outcome measures were gas exchange, pulmonary physiology, inflammatory markers, and histopathologic assessment score., Results: Lungs exposed for 2 h of warm ischaemia did not meet the criteria: PaO2 > 13 kPa required for donation compared with lungs subjected to 0 and 1 h of warm ischaemia (11.0 kPa vs. 14.2 kPa, P < 0.001). These lungs also developed an increased amount of foam and fluid in the airways. No differences in PaCO2, compliance, or pulmonary vascular resistance were observed., Conclusion: Results show that while lungs subjected to 0 or 1 h of warm ischaemia meet the criteria for transplantation based on EVLP evaluation, lungs subjected to 2 h of warm ischaemia did not.

Objectives: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD., Methods: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period)., Results: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated., Conclusions: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

In everyday life, we group and subdivide time to understand the sensory environment surrounding us. Organizing time in units, such as diurnal rhythms, phrases, and beat patterns, is fundamental to behavior, speech, and music. When listening to music, our perceptual system extracts and nests rhythmic regularities to create a hierarchical metrical structure that enables us to predict the timing of the next events. Foot tapping and head bobbing to musical rhythms are observable evidence of this process. In the special case of polyrhythms, at least two metrical structures compete to become the reference for these temporal regularities, rendering several possible beats with which we can synchronize our movements. While there is general agreement that tempo, pitch, and loudness influence beat perception in polyrhythms, we focused on the yet neglected influence of beat subdivisions, i.e., the least common denominator of a polyrhythm ratio. In three online experiments, 300 participants listened to a range of polyrhythms and tapped their index fingers in time with the perceived beat. The polyrhythms consisted of two simultaneously presented isochronous pulse trains with different ratios (2:3, 2:5, 3:4, 3:5, 4:5, 5:6) and different tempi. For ratios 2:3 and 3:4, we additionally manipulated the pitch of the pulse trains. Results showed a highly robust influence of subdivision grouping on beat perception. This was manifested as a propensity towards beats that are subdivided into two or four equally spaced units, as opposed to beats with three or more complex groupings of subdivisions. Additionally, lower pitched pulse trains were more often perceived as the beat. Our findings suggest that subdivisions, not beats, are the basic unit of beat perception, and that the principle underlying the binary grouping of subdivisions reflects a propensity towards simplicity. This preference for simple grouping is widely applicable to human perception and cognition of time., Competing Interests: The authors have declared that no competing interests exist.

Although scientific publication is often mandatory in medical professions, writing the first research article for publication is challenging, especially as medical curricula have only a minor focus on scientific writing. The aim was therefore to identify facilitators and barriers experienced by medical doctors writing their first scientific article for publication. An explorative inductive approach made use of semi-structured interviews for collecting data until saturation. Data were analyzed with systematic text condensation. Several barriers were identified: (a) writing in general; (b) writing in English; (c) dealing with content, structure, and presentation; and (d) navigating in the author group. Good supervision in the initial writing phase was a facilitating factor. Medical doctors requested a course in which they could work on their own articles and give feedback to fellow students. They valued skilled lecturers and individual supervision, and they wanted to learn about author instructions, how to present text correctly, and how to sell their core message. Their goal was to create a useful end product and to obtain European Credit Transfer System (ECTS) points. The facilitators and barriers that medical doctors experience when writing their first scientific article for publication and their course requests should be reflected in the learning objectives and content of future courses.

We report the first study on the thermal behavior of the stiffness of individual carbon nanotubes, which is achieved by measuring the resonance frequency of their fundamental mechanical bending modes. We observe a reduction of the Young's modulus over a large temperature range with a slope -(173±65)  ppm/K in its relative shift. These findings are reproduced by two different theoretical models based on the thermal dynamics of the lattice. These results reveal how the measured fundamental bending modes depend on the phonons in the nanotube via the Young's modulus. An alternative description based on the coupling between the measured mechanical modes and the phonon thermal bath in the Akhiezer limit is discussed.

The precise regulation of microRNA (miRNA) biogenesis is crucial for plant development, which requires core microprocessors and many fine tuners to coordinate their miRNA processing activity/specificity in fluctuating cellular environments. During de-etiolation, light triggers a dramatic accumulation of core microprocessors and primary miRNAs (pri-miRNAs) but decreases pri-miRNA processing activity, resulting in relatively constant miRNA levels. The mechanisms underlying these seemingly contradictory regulatory changes remain unclear. In this study, we identified forkhead-associated domain 2 (FHA2) as a light-stabilized suppressor of miRNA biogenesis. We found that FHA2 deficiency increased the level of mature miRNAs, accompanied by a reduction in pri-miRNAs and target mRNAs. Biochemical assays showed that FHA2 associates with the core microprocessors DCL1, HYL1, and SE, forming a complex to suppress their pri-miRNA processing activity. Further analyses revealed that FHA2 promotes HYL1 binding but inhibits the binding of DCL1-PAZ-RNase-RNA-binding domains (DCL1-PRR) to miRNAs, whereas FHA2 does not directly bind to these RNAs. Interestingly, we found that FHA2 protein is unstable in the dark but stabilized by light during de-etiolation. Consistently, disruption of FHA led to defects in light-triggered changes in miRNA expression and reduced the survival rate of de-etiolated seedlings after prolonged light deprivation. Collectively, these data suggest that FHA2 is a novel light-stabilized suppressor of miRNA biogenesis and plays a role in fine-tuning miRNA processing during de-etiolation., (Copyright © 2021 The Author. Published by Elsevier Inc. All rights reserved.)

Introduction: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN., Objective: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN., Method: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines., Results: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo., Discussion and Conclusion: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology., Level of Evidence: Level I, systematic review.

Our sensory systems provide complementary information about the multimodal objects and events that are the target of perception in everyday life. Professional musicians' specialization in the auditory domain is reflected in the morphology of their brains, which has distinctive characteristics, particularly in areas related to auditory and audio-motor activity. Here, we combined diffusion tensor imaging (DTI) with a behavioral measure of visually induced gain in pitch discrimination, and we used measures of cortical thickness (CT) correlations to assess how auditory specialization and musical expertise are reflected in the structural architecture of white and grey matter relevant to audiovisual processing. Across all participants (n = 45), we found a correlation (p < 0.001) between reliance on visual cues in pitch discrimination and the fractional anisotropy (FA) in the left inferior fronto-occipital fasciculus (IFOF), a structure connecting visual and auditory brain areas. Group analyses also revealed greater cortical thickness correlation between visual and auditory areas in non-musicians (n = 28) compared to musicians (n = 17), possibly reflecting musicians' auditory specialization (FDR < 10%). Our results corroborate and expand current knowledge of functional specialization with a specific focus on audition, and highlight the fact that perception is essentially multimodal while uni-sensory processing is a specialized task.

Since cheese is poor in energy for bacterial growth, it is believed that non-starter lactic acid bacteria growth and flavour development are supported by the nutrients from lysis of the starter culture. This study was performed to investigate the dynamics of interaction between starter and non-starter strains from cheese. A starter culture lysate was prepared by enzymatic digestion and tested as a growth substrate for Lactobacillus sp. strains. The two starter culture strains of Lactococcus lactis were also tested on the starter-lysate. All seventeen strains were individually inoculated at the level of 5.0 log 10 cfu mL -1 in M17 broth, with or without 10% starter-lysate, and incubated at 30 °C for 140 h. The optical density 600 nm was modelled with the primary log-transformed Logistic model with delay and lag phase duration, maximum specific growth rate as well as maximum population density obtained. Biphasic growth was mainly observed when the strains were able to utilize the starter-lysate as an energy source. To deal with the lack-of-fit related to the biphasic growth, the observed data points of the curve were divided after graphic evaluation and according to deviation of the residuals from the range ±0.05. Modelling was then performed in two phases by applying the same primary Logistic model in each of the two parts of the growth curve. Values of root-mean-square error and graphic evaluation indicated the good fitting of the data with the suggested approach. The growth of the two Lactococcus lactis strains was not affected by the starter-lysate. However, thirteen of the non-starter strains had their growth rates increased. The increase was greatest for Lactobacillus rhamnosus KU-LbR1, which reached maximum optical densities of 0.23 and 0.58 in the absence and the presence of starter-lysate, respectively. No effect of the starter-lysate was shown for the growth of Lactobacillus curvatus strains. The extend of the growth of non-starter strains on the starter-lysate was shown to be species and strain dependent., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Smart manufacturing, tailored by the 4th industrial revolution and forces like innovation, competition, and changing demands, lies behind the concurrent evolution (also known as co-evolution) of products, processes and production systems. Manufacturing companies need to adapt to ever-changing environments by simultaneously reforming and regenerating their product, process, and system models as well as goals and strategies to stay competitive. However, the ever-increasing complexity and ever-shortening lifecycles of product, process and system domains challenge manufacturing organization's conventional approaches to analysing and formalizing models and processes as well as management, maintenance and simulation of product and system life cycles. The digital twin-based virtual factory (VF) concept, as an integrated simulation model of a factory including its subsystems, is promising for supporting manufacturing organizations in adapting to dynamic and complex environments. In this paper, we present the demonstration and evaluation of previously introduced digital twin-based VF concept to support modelling, simulation and evaluation of complex manufacturing systems while employing multi-user collaborative virtual reality (VR) learning/training scenarios. The concept is demonstrated and evaluated using two different wind turbine manufacturing cases, including a wind blade manufacturing plant and a nacelle assembly line. Thirteen industry experts who have diverse backgrounds and expertise were interviewed after their participation in a demonstration. We present the experts' discussions and arguments to evaluate the DT-based VF concept based on four dimensions, namely, dynamic, open, cognitive, and holistic systems. The semi-structured conversational interview results show that the DT-based VF stands out by having the potential to support concurrent engineering by virtual collaboration. Moreover, DT-based VF is promising for decreasing physical builds and saving time by virtual prototyping (VP)., Competing Interests: Conflict of interestNo potential conflict of interest was reported by the authors and the stakeholders., (© The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature 2021.)

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) CC398 has emerged in humans throughout Europe and the USA during the last decade and is associated with the spread of LA-MRSA CC398 in production animals. In this study, we investigated the risk of subsequent hospitalization with an S. aureus-related diagnosis and death within the first 2 years after MRSA diagnosis. The study included 7,521 carriers of MRSA, an age-matched reference population of 376,041 individuals and 7,607 patients infected with MRSA. Hazard ratios (HR) for hospitalization with an S. aureus-related diagnosis were 4.09 (95% CI: 2.78-6.00) and for death 1.21 (95% CI: 0.80-1.83) in LA-MRSA CC398 carriers compared with the reference population. Comparing carriers of LA-MRSA CC398 and non-CC398 MRSA, HR for hospitalization was 0.61 (95% CI: 0.37-0.99) and death 0.25 (95% CI: 0.16-0.40), respectively. Patients initially diagnosed with LA-MRSA CC398 or non-CC398 MRSA infection differed from MRSA carriers in terms of older age, higher Charlson comorbidity index score and longer hospital stays. HR for subsequent hospitalization and death was similar regardless having infection with LA-MRSA CC398 or non-CC398 MRSA at the time of MRSA diagnosis. We established that MRSA CC398 carriers have a lower risk of hospitalization and death up to 2 years after MRSA diagnosis than non-CC398 MRSA carriers do. In contrast, MRSA carriage, regardless the MRSA strain is a burden in terms of hospitalization and death when compared to the background reference population. Further, we established that there are no differences in risk of subsequent hospitalization and death in patients initially diagnosed with MRSA CC398 or non-CC398 MRSA infection. We suggest that public health surveillance of MRSA clearly needs to distinguish between carriage and infection as well as strain type before any inference from number of cases to disease burden is made., (© 2020 Wiley-VCH GmbH.)

Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic β cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naïve to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care., (Copyright © 2020 Keindl, Fedotkina, du Plessis, Jain, Bergum, Mygind Jensen, Laustrup Møller, Falhammar, Nyström, Catrina, Jörneskog, Groop, Eliasson, Eliasson, Brismar, Nilsson, Berg, Appel and Lyssenko.)

Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.

This review summarises the knowledge of abdominal ectopic pregnancy (AEP), which is a rare condition with higher morbidity and mortalilty than other types of ectopic pregnancies. The condition can be primary, if the pregnancy implants directly on to an abdominal site, or it can be secondary after a tubar abortion. AEP differs from tubal pregnancies by a normal level of human chorionic gonadotropin and rare vaginal bleeding, which causes a diagnostic delay. In an early pregnancy the treatment is laparoscopic removal, but in second and third trimester pregnancies laparotomy is preferred, if possible preceded by MRI for mapping of vascular involvement and location of placenta.

This study was performed to investigate the presence of histamine forming bacteria in commercially available cheeses as well as to evaluate the histamine forming potential using in vitro models. Five long-time-ripened cheeses made from different milk types were analysed for histamine producing bacterial isolates. The ability of the isolates to produce histamine was tested by incubation at 37 °C for five days in a restricted media with a pH indicator. Changes in the amino-compound profile were investigated using ultra performance liquid chromatography. Only eight of 106 isolates were able to produce compounds raising the pH and seven of those were confirmed to be histamine producers. Despite the fact that all isolates were obtained from the same vintage Danish Gouda cheese, made from raw cow milk, the amino-compound profile as well as the response to different environmental conditions diverged between the isolates. Rep-PCR and 16S rRNA gene sequencing was used to further characterize the isolates. Pediococcus pentosaceus was for the first time reported to be a histamine producer in cheese. The presence of the histidine decarboxylase gene (hdcA) was confirmed by PCR amplification of the histidine decarboxylase gene in four of the isolates. The results indicate that evaluating the presence and concentration of histamine is not only a relevant parameter to evaluate quality and safety, but is also an important tool to classify histamine producers in cheese., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with comorbidity and decreased quality of life. The current treatment of PsA is non-steroid anti-inflammatory drugs or in more severe cases disease modifying antirheumatic drugs such as methotrexate or leflunomide, but these agents are often inadequately effective. Biologic tumour necrosis factor (TNF)-inhibitors are effective in the treatment of PsA. However, many patients lose efficacy or have an insufficient response to TNF-inhibitors. Biologic agents targeting interleukin-17A have shown encouraging clinical results.

Angiogenesis is considered integral to the reparative process after ischemic injury. The α v β₃ integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68 Ga-NODAGA-E[(cRGDyK)]₂ (RGD) is a positron-emission-tomography (PET) ligand targeted towards α v β₃ integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82 Rubidium ( 82 Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUV mean ) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUV mean : 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUV mean : 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated., Competing Interests: T.R., B.F., J.K., M.B.-L., J.M., T.E.C., M.J., K.P.H., C.H.M., J.P.G., P.H., A.K.: Has nothing to disclose. S.C.: Have a US patent pending on alginate hydrogel formulation.

During copy-editing, the y-axes of Fig. 2 (top) and Fig. 3 (top) were erroneously labelled mean BCG (d') in the version of the paper published as Online First. The correct label is meanCE (d').

Perception is fundamentally a multisensory experience. The principle of inverse effectiveness (PoIE) states how the multisensory gain is maximal when responses to the unisensory constituents of the stimuli are weak. It is one of the basic principles underlying multisensory processing of spatiotemporally corresponding crossmodal stimuli that are well established at behavioral as well as neural levels. It is not yet clear, however, how modality-specific stimulus features influence discrimination of subtle changes in a crossmodally corresponding feature belonging to another modality. Here, we tested the hypothesis that reliance on visual cues to pitch discrimination follow the PoIE at the interindividual level (i.e., varies with varying levels of auditory-only pitch discrimination abilities). Using an oddball pitch discrimination task, we measured the effect of varying visually perceived vertical position in participants exhibiting a wide range of pitch discrimination abilities (i.e., musicians and nonmusicians). Visual cues significantly enhanced pitch discrimination as measured by the sensitivity index d', and more so in the crossmodally congruent than incongruent condition. The magnitude of gain caused by compatible visual cues was associated with individual pitch discrimination thresholds, as predicted by the PoIE. This was not the case for the magnitude of the congruence effect, which was unrelated to individual pitch discrimination thresholds, indicating that the pitch-height association is robust to variations in auditory skills. Our findings shed light on individual differences in multisensory processing by suggesting that relevant multisensory information that crucially aids some perceivers' performance may be of less importance to others, depending on their unisensory abilities.

Background: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free of chronic lung allograft dysfunction (CLAD) as morbidity variables., Methods: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors. Donors were divided into three groups: group 1 included smokers, group 2 nonsmokers, and group 3 had unknown smoking status; these were further divided into three age groups: group A: 0 to 39 years; group B: 40 to 54 years; and group C: ≥55 years., Results: One hundred fifty-one donors were former or actual smokers, 175 were nonsmokers, and 128 had unknown smoking histories. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from a smoking donor. CLAD-free survival was identical in all smoking groups, and overall survival was better both for lungs from nonsmoking donors and donors with unknown smoking status compared to lungs from smoking donors. One hundred sixty-nine donors were in age group A, 203 in B, and 82 in C. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from donors older than 55 years. Overall survival as well as CLAD-free survival was significantly lower with donors ≥55 years., Conclusions: Donor smoking history and older donor age impact lung function, mortality, and CLAD-free survival after transplantation. Because of a shortage of organs, extended donor criteria may be considered while taking waiting list mortality into account., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ionotropic glutamate receptor antagonists are valuable tool compounds for studies of neurological pathways in the central nervous system. On the basis of rational ligand design, a new class of selective antagonists, represented by (2S,4R)-4-(2-carboxyphenoxy)pyrrolidine-2-carboxylic acid (1b), for cloned homomeric kainic acid receptors subtype 1 (GluK1) was attained (K i = 4 μM). In a functional assay, 1b displayed full antagonist activity with IC 50 = 6 ± 2 μM. A crystal structure was obtained of 1b when bound in the ligand binding domain of GluK1. A domain opening of 13-14° was seen compared to the structure with glutamate, consistent with 1b being an antagonist. A structure-activity relationship study showed that the chemical nature of the tethering atom (C, O, or S) linking the pyrrolidine ring and the phenyl ring plays a key role in the receptor selectivity profile and that substituents on the phenyl ring are well accommodated by the GluK1 receptor.

Introduction: The debate on non-medical male circumcision has gaining momentum during the past few years. The objective of this systematic review was to determine if circumcision, medical indication or age at circumcision had an impact on perceived sexual function in males., Methods: Systematic searches were performed in MEDLINE and Embase. The included studies compared long-term sexual function in circumcised and non-circumcised males, before and after circumcision, or compared different ages at circumcision. The quality of the studies was assessed according to the level of evidence (Grade A-D)., Results: Database and hand searches yielded 3,677 records. Inclusion criteria were fulfilled in 38 studies including two randomised trials. Overall, the only identified differences in sexual function in circumcised males were decreased premature ejaculation and increased penile sensitivity (Grade A-B). Following non-medical circumcision, no inferior sexual function was reported (A-B). Following medical circumcision, most outcomes were comparable (B); however, problems in obtaining an orgasm were increased (C) and erectile dysfunction was reported with inconsistency (D). A younger age at circumcision seemed to cause less sexual dysfunction than circumcision later in life., Conclusions: The hypothesis of inferior male sexual function following circumcision could not be supported by the findings of this systematic review. However, further studies on medical circumcision and age at circumcision are required.

In a previous study, a model was developed to describe the transfer and survival of Salmonella during grinding of pork (Møller, C.O.A., Nauta, M.J., Christensen, B.B., Dalgaard, P., Hansen, T.B., 2012. Modelling transfer of Salmonella typhimurium DT104 during simulation of grinding of pork. Journal of Applied Microbiology 112 (1), 90-98). The robustness of this model is now evaluated by studying its performance for predicting the transfer and survival of Salmonella spp. and Listeria monocytogenes during grinding of different types of meat (pork and beef), using two different grinders, different sizes and different numbers of pieces of meats to be ground. A total of 19 grinding trials were collected. Acceptable Simulation Zone (ASZ), visual inspection of the data, Quantitative Microbiological Risk Assessment (QMRA), as well as the Total Transfer Potential (TTP) were used as approaches to evaluate model performance and to access the quality of the cross contamination model predictions. Using the ASZ approach and considering that 70% of the observed counts have to be inside a defined acceptable zone of ±0.5 log10CFU per portion, it was found that the cross contamination parameters suggested by Møller et al. (2012) were not able to describe all 19 trials. However, for each of the collected grinding trials, the transfer event was well described when fitted to the model structure proposed by Møller et al. (2012). Parameter estimates obtained by fitting observed trials performed at different conditions, such as size and number of pieces of meat to be ground, may not be applied to describe cross contamination of unlike processing. Nevertheless, the risk estimates, as well as the TTP, revealed that the risk of disease may be reduced when the grinding of meat is performed in a grinder made of stainless steel (for all surfaces in contact with the meat), using a well-sharpened knife and holding at room temperatures lower than 4°C., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A novel transparent touch sensor was fabricated with a drop-on-demand inkjet printing technique on borosilicate glass and flexible polyethylene terephthalate (PET) substrates. Conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (, Pedot: PSS) and dielectric poly(methylsiloxane) were deposited on a desired area to form a capacitive touch sensor structure. The properties of the printed sensors (optical transparency, electrical resistance and touch sensing performance) were investigated with varying, Pedot: PSS printing passes. A novel transparent touch sensor fabricated with an all-inkjet-printing method is demonstrated for the first time. This process holds industrially viable potential to fabricate transparent touch sensors with an inkjet printing technique on both rigid and flexible substrates for a wide range of applications.

Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 Å resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8° and 2f a domain opening in GluK1-LBD of 17.0-17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate.

Two α-amino acid-functionalized quinoxalines, 1a (CNG-10301) and 1b (CNG-10300), of a quinoxaline moiety coupled to an amino acid moiety were designed, synthesized, and characterized pharmacologically. While 1a displayed low affinity at native AMPA, KA, and NMDA receptors, and at homomeric GluK1,3 receptors, the affinity for GluK2 was in the midmicromolar range (Ki = 136 μM), 1b displayed low to midmicromolar range binding affinity at all the iGluRs (Ki = 9-126 μM). In functional experiments (outside-out patches excised from transfected HEK293T cells), 100 μM 1a partially blocked GluK1 (33% peak response), while GluK2 was unaffected (96% peak response). Furthermore, 1a was shown not to be an agonist at GluK1 and GluK2 at 100 μM. On the other hand, 100 μM 1b fully antagonized GluK1 (8% peak response) but only partially blocked GluK2 (33% peak response). An X-ray structure at 2.3 Å resolution of 1b in the GluK1-LBD (ligand-binding domain) disclosed an unexpected binding mode compared to the predictions made during the design phase; the quinoxaline moiety remains to act as an amino acid bioisostere, but the amino acid moiety is oriented into a new area within the GluK1 receptor. The structure of the GluK1-LBD with 1b showed a large variation in domain openings of the three molecules from 25° to 49°, demonstrating that the GluK1-LBD is capable of undergoing major domain movements.

Objective: This study aims to evaluate the diagnostic efficiency of pattern recognition by transvaginal ultrasonography (TVS) and gel infusion sonography (GIS) for identifying endometrial pathology and to compare this setup with a standard setup of endometrial sampling (ES), hysteroscopy with pattern evaluation (HY(pattern)), or magnetic resonance imaging (MRI)., Methods: This study used a prospective cohort of 174 women with postmenopausal bleeding and endometrial thickness of 5 mm or greater. Resectoscopic biopsy (hysteroscopy with biopsy) samples or hysterectomy served as reference standard. Malignant and benign endometrial patterns were evaluated with TVS, GIS and HY(pattern) were then added. The efficiency of each diagnostic strategy, including ES and MRI findings (n = 83), was compared and evaluated against the reference standard., Results: ES, TVS, GIS, and HY(pattern) had high diagnostic efficiency (area under the curve) for malignancy diagnosis (ES, 0.90; TVS, 0.88; GIS, 0.92; HY(pattern), 0.91). When insufficient samples were incorporated, ES was less efficient than the other techniques. ES was not more efficient in the subgroup of women without localized lesions than in the subgroup of women with localized lesions. MRI and HY(pattern) added limited efficiency, whereas hysteroscopy with biopsy was most efficient., Conclusions: As a first-line technique, pattern recognition on TVS, GIS, and HY(pattern) correctly identifies 9 of 10 women with malignancy and is superior to pattern recognition on ES when insufficient samples are included. Endometrial pattern evaluated with TVS and GIS is a fast and efficient first-line diagnostic tool that outperforms ES in women with or without localized lesions. Malignant patterns on TVS/GIS should warrant fast-track evaluation, whereas women with benign patterns may be selected for office or operative hysteroscopy. A fast-track diagnostic setup based on pattern recognition is presented.

Background: Acute kidney injury (AKI) after cardiac surgery is common and is associated with increased mortality. We wanted to investigate if the arterial pressure or the use of norepinephrine during cardiopulmonary bypass were associated with AKI., Methods: A retrospective analysis of patients who underwent coronary artery bypass grafting with or without concomitant procedures was conducted. AKI was defined using the RIFLE criteria. Data on arterial pressure and use of norepinephrine during cardiopulmonary bypass were entered in a binary logistic regression model to control for possible perioperative confounders., Results: A total of 623 patients were included. Mean age was 68.3 ± 9.7 years and 81% were males. AKI was observed in 198 patients (32%). Mean arterial pressure was 47 ± 6 mmHg and 45 ± 6 mmHg (P = 0.008) in the AKI and no-AKI group, respectively. Norepinephrine was used more frequently and in higher amounts, during cardiopulmonary bypass, in patients who developed AKI. These differences in arterial pressures and use of norepinephrine between the groups were not found to be significant when entered in the binary logistic regression model., Conclusion: No independent relationship between arterial pressure or use of norepinephrine and AKI was found., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p = 0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0%, p = 0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts.

Objective: To propose a scoring system to predict endometrial cancer using different ultrasound image characteristics at gray-scale, with and without enhancement by gel infusion, and Doppler transvaginal sonography (TVS) and to evaluate intra- and interobserver variability in assessment of these characteristics., Method: Unenhanced TVS, Doppler examinations and gel infusion sonography (GIS) were performed prospectively in 174 consecutive postmenopausal women with endometrial thickness ≥ 5 mm. The reference standard in all women was hysteroscopy or hysterectomy with pathological evaluation of the malignancy. The presence of various ultrasound pattern characteristics indicative of endometrial malignancy and intra- and interobserver variability in their assessment were evaluated. Multivariate logistic regression was used to correlate image and clinical parameters to presence of endometrial cancer., Results: A simple Doppler flow score (which considered only presence of vascularity and not presence of single/double dominant vessel, multiple vessels, large vessels, color splash or densely packed vessels) had an area under the receiver-operating characteristics curve (AUC) of 0.83 in the prediction of endometrial cancer. Models including endometrial thickness, Doppler score and interrupted endomyometrial junction on unenhanced TVS predicted endometrial cancer with an AUC of 0.95 (95% CI, 0.92-0.99) and, with addition of irregular surface on GIS, the AUC was 0.97 (95% CI, 0.94-0.99). A risk of endometrial cancer (REC) scoring system based on body mass index, Doppler score, endometrial thickness and interrupted endomyometrial junction on unenhanced TVS and irregular surface at GIS performed very well at identifying endometrial cancer; at a REC-score of ≥ 4 the sensitivity for detection of endometrial cancer was 91% and specificity was 94%. Observers agreed in 82.3% of cases (kappa, 0.63 (0.48-0.78)) when subjective parameters were analyzed in stored videoclips., Conclusion: Our observer-dependent proposed scoring system seems to perform well in the prediction of endometrial cancer and should be tested in future studies., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Some foreign prostitutes are victims of traffiquing, do not speak Danish and are not familiar with the services offered in the Danish Health Service. The mobile health initiative localises foreign prostitutes and offers health checks and help in case of illness or pregnancy. The article reports method and findings from the first two-year period with this initiative.

Objective: Fibroblast growth factor 21 (FGF21) is a metabolic regulator of glucose and lipid metabolism. The physiological role of FGF21 is not yet fully elucidated, however, administration of FGF21 lowers blood glucose in diabetic animals. Moreover, increased levels of FGF21 are found in obese and diabetic rodents and humans compared with lean/non-diabetic controls., Methods: Adult male rhesus macaque monkeys were chronically maintained on a high-fat diet (HFD) or a standard diet (control, CTR). Plasma levels of FGF21, triglycerides and cholesterol were measured and body weight was record. Glucose-stimulated insulin secretion (GSIS) and glucose clearance was determined during an intravenous glucose tolerance test. Furthermore, expression of FGF21 and its receptors were determined in liver, pancreas, three white adipose tissues (WATs) and two skeletal muscles., Results: A cohort of the high-fat fed monkeys responded to the HFD with increasing body weight, plasma lipids, total cholesterol, GSIS and decreased glucose tolerance. These monkeys were termed HFD sensitive. Another cohort of monkeys did not become obese and maintained normal insulin sensitivity. These animals were defined as HFD resistant. Plasma FGF21 levels were significantly increased in all HFD fed monkeys compared with the CTR group. The HFD-sensitive monkeys showed a significant increase in FGF21 mRNA expression in all examined tissues compared with CTR, whereas FGF21 expression in the HFD-resistant group was only increased in the liver, pancreas and the retroperitoneal WAT. In the WAT, the co-receptor β-klotho was downregulated in the HFD-sensitive monkeys compared with the HFD-resistant group., Conclusion: This study demonstrates that HFD changes FGF21 and FGF21 receptor expression in a tissue-specific manner in rhesus monkeys; differential regulation is moreover observed between HFD-sensitive and -resistant monkeys. Monkeys that maintain normal levels of the FGF21 co-receptor β-klotho in the WAT on HFD were protected toward development of dyslipidemia and hyperglycemia.

This study was undertaken to model and predict growth of Salmonella and the dominating natural microbiota, and their interaction in ground pork. Growth of Salmonella in sterile ground pork at constant temperatures between 4 °C and 38 °C was quantified and used for developing predictive models for lag time, max. specific growth rate and max. population density. Data from literature were used to develop growth models for the natural pork microbiota. Challenge tests at temperatures from 9.4 to 24.1 °C and with Salmonella inoculated in ground pork were used for evaluation of interaction models. The existing Jameson-effect and Lotka-Volterra species interaction models and a new expanded Jameson-effect model were evaluated. F-test indicated lack-of-fit for the classical Jameson-effect model at all of the tested temperatures and at 14.1-20.2 °C this was caused by continued growth of Salmonella after the natural microbiota had reached their max. population density. The new expanded Jameson-effect model and the Lotka-Volterra model performed better and appropriately described the continued but reduced growth of Salmonella after the natural microbiota had reached their max. population density. The expanded Jameson-effect model is a new and simple species interaction model, which performed as well as the more complex Lotka-Volterra model., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the accuracy of different preoperative modalities for staging of endometrial cancer to restrict extensive surgery to patients at high risk of metastatic disease., Setting: Aarhus University Hospital., Population: 156 women referred in 2006-2011 because of atypical endometrial hyperplasia (G0) or endometrial cancer., Methods: Patients were offered preoperative transvaginal ultrasonography (TVS), magnetic resonance imaging (MRI), and hysteroscopic-directed biopsies from the uterine tumor and cervix. Final pathology of the removed uterus was the reference standard. Patients were divided into low risk (<50% myometrial invasion, and grades 0, 1, 2, and no cervical invasion) or high risk (all others)., Main Outcome Measures: Accuracy, sensitivity, specificity, positive/negative predictive value., Results: Patients were aged 32-88 years, with a mean body mass index of 29. At final pathology 81% had cancer and 19% G0 or no residual tumor; 54% were high risk. Hysteroscopy-directed biopsies had a higher accuracy (92%) than endometrial biopsy (58%) for differentiating G0 from cancer (p < 0.001); grade 3 tumor identification had similar accuracy (93 vs. 92%). Deep myometrial invasion was estimated with higher accuracy by MRI (82%) than TVS (74%) (p < 0.02). For cervical involvement, hysteroscopy-directed biopsies had higher accuracy (94%) than MRI (84%,) and TVS (80%) (p < 0.02). Accuracy for identifying high-risk women was highest (83%) using a combination of MRI and hysteroscopic-directed biopsies, compared with TVS and endometrial biopsy (72%) (p < 0.05)., Conclusion: Preoperative staging with MRI and hysteroscopy-directed biopsy can identify eight of 10 women with high risk of lymph node metastases and spare eight of 10 low-risk women extended surgery., (© 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)