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Purpose: To identify the sperm preparation procedure that selects the best sperm population for medically assisted reproduction. Methods: Prospective observational study comparing the effect of four different sperm selection procedures on various semen parameters. Unused raw semen after routine diagnostic analysis was split in four fractions and processed by four different methods: (1) density gradient centrifugation (DGC), (2) sperm wash (SW), (3) DGC followed by magnetic activated cell sorting (MACS), and (4) using a sperm separation device (SSD). Each fraction was analyzed for progressive motility, morphology, acrosome index (AI), and DNA fragmentation index (DFI). Results: With DGC as standard of care in intraclass correlation coefficient analysis, only SSD was in strong disagreement regarding progressive motility and DFI [0.26, 95%CI (− 0.2, 0.58), and 0.17, 95%CI (− 0.19, 0.45), respectively]. When controlling for abstinence duration, DFI was significantly lower after both MACS and SSD compared to DGC [− 0.27%, 95%CI (− 0.47, − 0.06), p = 0.01, and − 0.6%, 95%CI (− 0.80, − 0.41), p < 0.001, respectively]. Further comparisons between SSD and MACS indicate significantly less apoptotic cells [Median (IQR) 4 (5), 95%CI (4.1, − 6.8) vs Median (IQR) 5 (8), 95%CI (4.9, − 9.2), p < 0.001, respectively] and dead cells [Median (IQR) 9.5 (23.3), 95%CI (13.2, − 22.4) vs Median (IQR) 22 (28), 95%CI (23.1, − 36.8), p < 0.001, respectively] in the SSD group. Conclusion: The selection of a population of highly motile spermatozoa with less damaged DNA from unprocessed semen is ideally performed with SSD. Question remains whether this method improves the embryological outcomes in the IVF laboratory. [ABSTRACT FROM AUTHOR]

This study represents the first extensive residue analysis of prehistoric pottery from northern Belgium. It examines pottery use and culinary practices across the Mesolithic-Neolithic transition, from the late 6th to the early 4th millennium cal BC. Residue analyses were performed on more than 200 samples from nine archaeological sites, representing different cultural groups from this transitional phase. This includes the analysis of charred food residues encrusted on the vessel surfaces by elemental analysis-isotope ratio mass spectrometry (EA-IRMS), gas chromatography-mass spectrometry (GC-MS), stereomicroscopic analysis and Scanning Electron Microscopy (SEM), as well as the analysis of absorbed lipids by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). This study provides the first evidence of ruminant dairy fats in Early Neolithic Limburg pottery, supporting the hypothesis that this pottery was produced and used by LBK farmers rather than hunter-gatherer populations. The first indigenous pottery of the Swifterbant culture was frequently used to process freshwater fish (often together with plant foods) and ruminant meat, although several of the studied vessels likely contained mixtures of resources which could also include porcine products. Ruminant dairy is nearly absent from this pottery. Similar results were obtained for pottery of the subsequent Michelsberg culture/Group of Spiere of the late 5th and early 4th millennium cal BC. The limited presence of ruminant dairy fats in this pottery contrasts with the findings for Middle Neolithic pottery from neighbouring regions, providing further evidence for the existence of regional variations in pottery use or culinary practices throughout prehistoric NW Europe. However, our current view of pottery use during the Mesolithic-Neolithic transition in northern Belgium might be biased by the difficulties in distinguishing between wild and domesticated ruminant adipose fats as well as in detecting plant foods through lipid residue analysis. [ABSTRACT FROM AUTHOR]

Honey bees are commonly co-exposed to pesticides during crop pollination, including the fungicide captan and neonicotinoid insecticide thiamethoxam. We assessed the impact of exposure to these two pesticides individually and in combination, at a range of field-realistic doses. In laboratory assays, mortality of larvae treated with captan was 80–90% greater than controls, dose-independent, and similar to mortality from the lowest dose of thiamethoxam. There was evidence of synergism (i.e., a non-additive response) from captan-thiamethoxam co-exposure at the highest dose of thiamethoxam, but not at lower doses. In the field, we exposed whole colonies to the lowest doses used in the laboratory. Exposure to captan and thiamethoxam individually and in combination resulted in minimal impacts on population growth or colony mortality, and there was no evidence of synergism or antagonism. These results suggest captan and thiamethoxam are each acutely toxic to immature honey bees, but whole colonies can potentially compensate for detrimental effects, at least at the low doses used in our field trial, or that methodological differences of the field experiment impacted results (e.g., dilution of treatments with natural pollen). If compensation occurred, further work is needed to assess how it occurred, potentially via increased queen egg laying, and whether short-term compensation leads to long-term costs. Further work is also needed for other crop pollinators that lack the social detoxification capabilities of honey bee colonies and may be less resilient to pesticides. [ABSTRACT FROM AUTHOR]

To study hiring discrimination against cancer survivors, we conduct a vignette experiment in which American and British professionals recruited via Prolific evaluate fictitious job candidates. Candidates differed by periods of non-employment in their career, including non-employment due to suffering from cancer. We study the effect of cancer experiences on professionals' hirability ratings, as well as its effect on underlying candidate perceptions, related to various potential forms of stigma identified in the literature. We find that employment opportunities are lower for candidates with a history of cancer, compared to candidates without such a gap. This penalty is particularly explained by perceptions that these candidates will have higher sick leave probabilities and create additional costs. However, relative to candidates with a comparable gap due to depression or personal reasons, former cancer patients are less stigmatised, with relatively favourable assessments of their emotional abilities, social abilities, motivation and positive impact on workplace culture. [ABSTRACT FROM AUTHOR]

Quantum computing aims at exploiting quantum phenomena to efficiently perform computations that are unfeasible even for the most powerful classical supercomputers. Among the promising technological approaches, photonic quantum computing offers the advantages of low decoherence, information processing with modest cryogenic requirements, and native integration with classical and quantum networks. So far, quantum computing demonstrations with light have implemented specific tasks with specialized hardware, notably Gaussian boson sampling, which permits the quantum computational advantage to be realized. Here we report a cloud-accessible versatile quantum computing prototype based on single photons. The device comprises a high-efficiency quantum-dot single-photon source feeding a universal linear optical network on a reconfigurable chip for which hardware errors are compensated by a machine-learned transpilation process. Our full software stack allows remote control of the device to perform computations via logic gates or direct photonic operations. For gate-based computation, we benchmark one-, two- and three-qubit gates with state-of-the art fidelities of 99.6 ± 0.1%, 93.8 ± 0.6% and 86 ± 1.2%, respectively. We also implement a variational quantum eigensolver, which we use to calculate the energy levels of the hydrogen molecule with chemical accuracy. For photon native computation, we implement a classifier algorithm using a three-photon-based quantum neural network and report a six-photon boson sampling demonstration on a universal reconfigurable integrated circuit. Finally, we report on a heralded three-photon entanglement generation, a key milestone toward measurement-based quantum computing. A versatile cloud-accessible single-photon-based quantum computing machine is developed, which shows a six-photon sampling rate of 4 Hz over weeks. Heralded generation of a three-photon Greenberger–Horne–Zeilinger state—a key milestone toward measurement-based quantum computing—is implemented. [ABSTRACT FROM AUTHOR]

Background: Several diagnostic prediction models to help clinicians discriminate between benign and malignant adnexal masses are available. This study is a head-to-head comparison of the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model with that of the Risk of Ovarian Malignancy Algorithm (ROMA). Methods: This is a retrospective study based on prospectively included consecutive women with an adnexal tumour scheduled for surgery at five oncology centres and one non-oncology centre in four countries between 2015 and 2019. The reference standard was histology. Model performance for ADNEX and ROMA was evaluated regarding discrimination, calibration, and clinical utility. Results: The primary analysis included 894 patients, of whom 434 (49%) had a malignant tumour. The area under the receiver operating characteristic curve (AUC) was 0.92 (95% CI 0.88–0.95) for ADNEX with CA125, 0.90 (0.84–0.94) for ADNEX without CA125, and 0.85 (0.80–0.89) for ROMA. ROMA, and to a lesser extent ADNEX, underestimated the risk of malignancy. Clinical utility was highest for ADNEX. ROMA had no clinical utility at decision thresholds <27%. Conclusions: ADNEX had better ability to discriminate between benign and malignant adnexal tumours and higher clinical utility than ROMA. Clinical trial registration: clinicaltrials.gov NCT01698632 and NCT02847832. [ABSTRACT FROM AUTHOR]

This paper examines the impact of a shift in focus from political praxis to trauma work in the context of a failed democratisation movement. It investigates the various phenomena which emerge when intellectuals, under the traumatic impact of violence and atrocities, place trauma narration at the core of their interventions. Drawing on document analysis, participant observation and semi-structured interviews with twenty nine exiled Syrian intellectuals in Paris and Berlin who had participated in the revolutionary movement of 2011, the paper suggests that an inversion of the normative power structures pertaining to how intellectuals relate to their publics occurs when they adopt, under conditions of extreme violence and trauma, what we call a radically embedded positionality vis-à-vis 'the people'. This results in the dismantling of previous figurations of the 'militant intellectual' along with praxis-focused notions of the 'responsibility of intellectuals', ultimately undermining their ideational influence upon domestic publics and weakening their political impact and critical role within a revolutionary movement. [ABSTRACT FROM AUTHOR]

The burnout literature has focused on the determinants of burnout, whereas its careers consequences remain understudied. Therefore, we investigate whether recently burned-out individuals differ in job preferences from non-burned-out workers. We link these differences in preferences with (1) perceptions of job demands and resources, as well as (2) the weighting of such perceptions. To this end, a sample of 582 employees varying in their history of burnout judged job offers with manipulated characteristics in terms of their willingness to apply as well as perceived job demands and resources. We find that recently burned-out employees appreciate possibilities to telework and fixed feedback relatively more, while being relatively less attracted to learning opportunities. These findings can be partially explained by differences in the jobs’ perceived resources. [ABSTRACT FROM AUTHOR]

We identify the causal effects of three types of internships (mandatory intra-curricular, voluntary intra-curricular, and voluntary extra-curricular) among university graduates on job interview and hiring chances, and explore the mechanisms underlying these effects. To this end, we perform a vignette experiment among HR professionals in Belgium. Our results indicate that internships improve one's job interview and hiring chances, with voluntary extra-curricular internships having the strongest effect. With respect to the mechanisms, we find that internships improve employers' perceptions about the job seekers' skills acquired during the educational career, their pre-existing abilities and motivations, and their knowledge of the job content and working conditions. The first two types of perceptions are also found to be strong predictors of the hiring outcomes. The effects of internships on hiring chances are not found to be reduced or reinforced by the presence of other work experiences (student work, volunteering). [ABSTRACT FROM AUTHOR]

Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance indicating that human-mediated transport may serve as a pathway of the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate. [ABSTRACT FROM AUTHOR]

Autonomous robots start to be integrated in human environments where explicit and implicit social norms guide the behavior of all agents. To assure safety and predictability, these artificial agents should act in accordance with the applicable social norms. However, it is not straightforward to define these rules and incorporate them in an agent's policy. Particularly because social norms are often implicit and environment specific. In this paper, we propose a novel iterative approach to extract a set of rules from observed human trajectories. This hybrid method combines the strengths of inverse reinforcement learning and inductive logic programming. We experimentally show how our method successfully induces a compact logic program which represents the behavioral constraints applicable in a Tower of Hanoi and a traffic simulator environment. The induced program is adopted as prior knowledge by a model-free reinforcement learning agent to speed up training and prevent any social norm violation during exploration and deployment. Moreover, expressing norms as a logic program provides improved interpretability, which is an important pillar in the design of safe artificial agents, as well as transferability to similar environments. [ABSTRACT FROM AUTHOR]

Carbofuran is a pesticide widely used in agricultural context to kill insects, mites, and flies by ingestion or contact. Along with literature review, we aimed to (i) present the clinical, autopsy, and toxicological findings of carbofuran self-poisonings in two 69-year-old twins, resulting in the death of one of them and (ii) assess carbofuran metabolite distribution using molecular networking. Quantitative analysis of carbofuran and its main metabolites (3-hydroxycarbofuran and 3-ketocarbofuran) was carried out using an original liquid chromatography-tandem mass spectrometry method on biological samples (cardiac or peripheral blood, urine, bile, and gastric contents). Toxicological analysis of post-mortem samples (twin 1) highlighted high concentrations of carbofuran and its metabolites in cardiac blood, bile, and gastric contents. These compounds were also quantified in blood and/or urine samples of the living brother (twin 2), confirming poisoning. Using molecular networking approach to facilitate visualization of mass spectrometry datasets and sample-to-sample comparisons, we detected two more metabolites (7-phenol-carbofuran and 3-hydroxycarbofuran glucuronide) in bile (twin 1) and urine (twin 2). These results highlight the value of (i) these compounds as carbofuran consumption markers and (ii) bile samples in post-mortem analysis to confirm poisoning. From an analytical point of view, molecular networking allowed the detection and interpretation of carbofuran metabolite ammonium adducts which helped to confirm their identification annotations, as well as their structural data. From a clinical point of view, the different outcomes between the two brothers are discussed. Overall, these cases provide novel information regarding the distribution of carbofuran and its metabolites in poisoning context. [ABSTRACT FROM AUTHOR]

Research using data on offline couple formation has confirmed predictions from evolutionary psychology that women (not men) attach value to the earnings potential of a potential partner. In this study, we examine whether the partner preferences with respect to earnings potential survive in an online context with fewer search and social frictions. We did this by means of a field experiment on the popular mobile dating app Tinder. Thirty-two fictitious Tinder profiles that randomly differed in job status and job prestige were evaluated by 4800 other, real Tinder users. We find that both men and women do not use job status or job prestige as a determinant of whom to show initial interest in on Tinder. However, we do find evidence that, after this initial phase, men less frequently start a conversation with women when those women are unemployed. Still, also then men do not care about the particular job prestige of employed women. [ABSTRACT FROM AUTHOR]

Inversions, i.e. a change in orientation of a segment of DNA, are a recognized cause of human diseases which remain overlooked due to their balanced nature. Inversions can have severe or more subtle impacts on gene expression. We describe two families that exemplify these aspects and underline the need for inversion detection in routine diagnosis. The first family (F1) displayed a sibship with two constitutional mismatch repair deficiency patients and a family history of colon cancer in the paternal branch. The second family (F2) displayed a severe history of Lynch syndrome. These families were analyzed using a whole gene panel (WGP) strategy i.e. including colon cancer genes with their intronic and flanking genomic regions. In F1, a PMS2 inversion encompassing the promoter region to intron 1 and a PMS2 splice variant were found in the maternal and paternal branch, respectively. In F2, we described the first MSH6 inversion, involving the 5′ part of MSH6 and the 3′ part of the nearby gene ANXA4. Inversion detection mandates genomic sequencing, but makes a valuable contribution to the diagnostic rate. WGP is an attractive strategy as it maximizes the detection power on validated genes and keeps sufficient depth to detect de novo events. [ABSTRACT FROM AUTHOR]

This study examines the direct and indirect impact (via educational achievement) of student work during secondary education on later employment outcomes. To this end, we jointly model student work and later schooling and employment outcomes as discrete choices, while correcting for these outcomes' unobserved determinants. Using unique longitudinal Belgian data, we find that pupils who work during the summer holidays are more likely to be employed three months after leaving school. This premium to student work in secondary education is higher when pupils also work during the school year. Decomposing this total effect shows that the direct return to student work during secondary education overcompensates its non-positive indirect effect via educational achievement. This effect is also found to decline over time, with the premium to a combination of work during the summer and the school year becoming statistically insignificant five years after graduation. [ABSTRACT FROM AUTHOR]

Colonial breeding provides benefits such as reduced predation risk, but also entails costs due to the enhanced levels of competition. In particular, it may require a significant amount of time and energy to establish a territory at the onset of reproduction, which in turn can impose carry-over effects on subsequent reproductive investments. Here we made use of GPS tracking devices to test how a colonial breeder, the lesser black-backed gull (Larus fuscus), balances its time investment between territorial and foraging activities throughout the pre-laying period, and investigated possible fitness consequences. As hypothesized, individuals that spent more time in their territories reduced their foraging time, foraged closer to the colony, and spent less time commuting during foraging trips. Although males initially invested more time in establishing a territory, both sexes gradually spent more time in their territory as the onset of egg laying, an energetically demanding period, approached. Furthermore, males that exhibited a higher territory attendance alleviated the females' time constraints for foraging and their partners laid larger eggs. Our results highlight the importance of quantifying carry-over effects related to time budgets during the (often understudied) pre-laying period, to better comprehend fitness consequences of colonial breeding. [ABSTRACT FROM AUTHOR]

While a considerable number of employees across the globe are being forced to work from home due to the COVID-19 crisis, it is a guessing game as to how they are experiencing this current surge in telework. Therefore, we examined employee perceptions of telework on various life and career aspects, distinguishing between typical and extended telework during the COVID-19 crisis. To this end, we conducted a state-of-the-art web survey among Flemish employees. Notwithstanding this exceptional time of sudden, obligatory and high-intensity telework, our respondents mainly attribute positive characteristics to telework, such as increased efficiency and a lower risk of burnout. The results also suggest that the overwhelming majority of the surveyed employees believe that telework (85%) and digital conferencing (81%) are here to stay. In contrast, some fear that telework diminishes their promotion opportunities and weakens ties with their colleagues and employer. [ABSTRACT FROM AUTHOR]

When managed bee colonies are brought to farms for crop pollination, they can be exposed to pesticide residues. Quantifying the risk posed by these exposures can indicate which pesticides are of the greatest concern and helps focus efforts to reduce the most harmful exposures. To estimate the risk from pesticides to bees while they are pollinating blueberry fields, we sampled blueberry flowers, foraging bees, pollen collected by returning honey bee and bumble bee foragers at colonies, and wax from honey bee hives in blooming blueberry farms in southwest Michigan. We screened the samples for 261 active ingredients using a modified QuEChERS method. The most abundant pesticides were those applied by blueberry growers during blueberry bloom (e.g., fenbuconazole and methoxyfenozide). However, we also detected highly toxic pesticides not used in this crop during bloom (or other times of the season) including the insecticides chlorpyrifos, clothianidin, avermectin, thiamethoxam, and imidacloprid. Using LD50 values for contact and oral exposure to honey bees and bumble bees, we calculated the Risk Quotient (RQ) for each individual pesticide and the average sample RQ for each farm. RQ values were considered in relation to the U.S. Environmental Protection Agency acute contact level of concern (LOC, 0.4), the European Food Safety Authority (EFSA) acute contact LOC (0.2) and the EFSA chronic oral LOC (0.03). Pollen samples were most likely to exceed LOC values, with the percent of samples above EFSA's chronic oral LOC being 0% for flowers, 3.4% for whole honey bees, 0% for whole bumble bees, 72.4% for honey bee pollen in 2018, 45.4% of honey bee pollen in 2019, 46.7% of bumble bee pollen in 2019, and 3.5% of honey bee wax samples. Average pollen sample RQ values were above the EFSA chronic LOC in 92.9% of farms in 2018 and 42.9% of farms in 2019 for honey bee collected pollen, and 46.7% of farms for bumble bee collected pollen in 2019. Landscape analyses indicated that sample RQ was positively correlated with the abundance of apple and cherry orchards located within the flight range of the bees, though this varied between bee species and landscape scale. There was no correlation with abundance of blueberry production. Our results highlight the need to mitigate pesticide risk to bees across agricultural landscapes, in addition to focusing on the impact of applications on the farms where they are applied. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary factor (F) XIII-deficiency is a known risk factor for postoperative complications, but data of acquired FXIII-deficiency in malignancies are limited. Therefore, we evaluated the role of acquired FXIII-deficiency in surgery for advanced epithelial ovarian cancer (EOC). Materials and methods: We performed a retrospective analysis of patients with known serum FXIII status and treatment between 2011 and 2018 at our center. We defined cohorts according to FXIII with values > 75% as normal (group A), 55–75% as reduced (group B) and < 55% as low (group C). Complications were classified according to the Clavien–Dindo Classification, class III–V complications were defined as severe. Results: 347 patients with EOC were identified. 180 patients (51.2%) were in group A, 82 patients (23.6%) in group B, and 85 patients (24.4%) in group C. Lower levels of FXIII were associated with higher amount of ascites, FIGO IV, high grade serous histology, low albumin, and higher CA-125 levels. Regarding intraoperative variables, low FXIII was associated with longer duration of surgery, higher blood loss, higher surgical complexity score/number of bowel anastomosis and a higher probability for macroscopic residual disease. The risk of severe complications in group A was 12.2%, 24.4% in group B, and 31.8% in group C. In a multivariate model, low FXIII (OR 2.8), > 1 bowel anastomosis (OR 2.7), age-adjusted Charlson comorbidity index ≥ 4 (OR 3.6) and a longer duration of surgery (> 285 min.) were significant predictive factors for severe complications. Conclusion: FXIII is associated with tumor and treatment burden. A low level of FXIII is associated with postoperative complications. The knowledge about the presurgical serum FXIII-level might be helpful to plan the treatment strategy. [ABSTRACT FROM AUTHOR]

International trade in plants and climate change are two of the main factors causing damaging tree pests (i.e. fungi and insects) to spread into new areas. To mitigate these risks, a large-scale assessment of tree-associated fungi and insects is needed. We present records of endophytic fungi and insects in twigs of 17 angiosperm and gymnosperm genera, from 51 locations in 32 countries worldwide. Endophytic fungi were characterized by high-throughput sequencing of 352 samples from 145 tree species in 28 countries. Insects were reared from 227 samples of 109 tree species in 18 countries and sorted into taxonomic orders and feeding guilds. Herbivorous insects were grouped into morphospecies and were identified using molecular and morphological approaches. This dataset reveals the diversity of tree-associated taxa, as it contains 12,721 fungal Amplicon Sequence Variants and 208 herbivorous insect morphospecies, sampled across broad geographic and climatic gradients and for many tree species. This dataset will facilitate applied and fundamental studies on the distribution of fungal endophytes and insects in trees. Measurement(s) metagenomics analysis • Cytochrome C Oxidase Subunit 1 Technology Type(s) amplicon sequencing • Dideoxy Chain Termination DNA Sequencing Factor Type(s) tree species • geographic location • mean annual temperature • mean annual precipitation Sample Characteristic - Organism Fungi • Insecta Sample Characteristic - Environment dormant tree twigs Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16764229 [ABSTRACT FROM AUTHOR]

Purpose: The chemotherapy response score (CRS) is a histopathological tool to evaluate response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (OC). We critically evaluated the clinical value of CRS and compared its predictive power to standard serological (CA125) and radiological response. Methods: A retrospective analysis of 277 OC patients, who received primary chemotherapy, was performed. CRS, serological, and radiological findings were correlated with progression-free (PFS) and overall survival (OS). Results: CRS could be determined in 172 of 277 patients (62.1%). In patients with CRS3, a longer median PFS and OS was observed compared with CRS1/2 patients (31.2 vs. 18.9, P < 0.001; 55.0 vs. 36.1 months, P = 0.050). CA125 and radiological response evaluation were also predictive for PFS and OS. Patients with serological and radiological complete response showed longer PFS (23.0 vs. 14.4, P = 0.011; 21.4 vs. 9.6 months, P < 0.001) and OS (49.5 vs. 29.0, P = 0.003; 45.0 vs. 12.9 months, P < 0.001). Patients with pathological complete response (pCR) had the best median PFS (52.8 months), even compared with non-pCR CRS3 (27.8 months). In the total study cohort, serological, and radiological complete response was better at predicting PFS (hazard ratio 2.23 and 2.77). Conclusion: In this study, evaluation of response to chemotherapy by CRS was not superior to conventional methods (CA125 or radiology). Independent of the evaluation method, response to NACT was predictive of PFS and OS. We observed no added value for CRS as a prognostic marker. The clinical relevance of CRS should be discussed, as no therapeutic consequences result from CRS evaluation. [ABSTRACT FROM AUTHOR]

Purpose: Current guidelines for Lynch syndrome detection in endometrial cancer (EC) patients rely either on risk evaluation, based on personal/family history, or detection of mismatch repair (MMR) deficiency on tumor tissue. We present a combined screening algorithm for Lynch syndrome. Methods: In this study, 213 consecutive patients treated for EC at Kliniken Essen-Mitte between 2014 and 2018 were included. Personal/family history was evaluated by the Amsterdam II, revised Bethesda/German-DKG criteria and prediction model PREMM5. MMR testing was performed by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) based microsatellite analysis on tumor tissue. MLH1 promoter methylation analysis was performed in case of MLH1 loss or microsatellite instability. Results: Based on personal/family history 2/213 (Amsterdam II), 31/213 (revised Bethesda/German-DKG) and 149/213 (PREMM5) patients were identified as at risk for Lynch syndrome. MMR analysis was performed by IHC in 51.2%, by PCR in 32.4%, and in 16.4% of patients both methods were used. MMR deficiency was detected in 20.6% (44/213). Methylation analysis was performed in 27 patients of whom, 22 (81.4%) showed MLH1 promoter hypermethylation. Only 9% of MMR deficient patients were identified as at risk for Lynch syndrome by the revised Bethesda/German-DKG criteria. A pathogenic germline mutation was discovered in 3 out of 20 patients that underwent genetic testing. None of these patients were younger than 50 years or had a family history of Lynch syndrome-associated malignancies. Conclusion: General MMR assessment is a feasible strategy to improve the detection of Lynch Syndrome in patients with EC. [ABSTRACT FROM AUTHOR]

Bees are critical for crop pollination, but there is limited information on levels and sources of pesticide exposure in commercial agriculture. We collected pollen from foraging honey bees and bumble bees returning to colonies placed in blooming blueberry fields with different management approaches (conventional, organic, unmanaged) and located across different landscape settings to determine how these factors affect pesticide exposure. We also identified the pollen and analyzed whether pesticide exposure was correlated with corbicular load composition. Across 188 samples collected in 2 years, we detected 80 of the 259 pesticide active ingredients (AIs) screened for using a modified QuEChERS method. Detections included 28 fungicides, 26 insecticides, and 21 herbicides. All samples contained pesticides (mean = 22 AIs per pollen sample), with pollen collected from bees on conventional fields having significantly higher average concentrations (2019 mean = 882.0 ppb) than those on unmanaged fields (2019 mean = 279.6 ppb). Pollen collected by honey bees had more AIs than pollen collected by bumble bees (mean = 35 vs. 19 AIs detected at each farm, respectively), whereas samples from bumble bees had higher average concentrations, likely reflecting differences in foraging behavior. Blueberry pollen was more common in pollen samples collected by bumble bees (25.9% per sample) than honey bees (1.8%), though pesticide concentrations were only correlated with blueberry pollen for honey bees. Pollen collected at farms with more blueberry in the surrounding landscape had higher pesticide concentrations, mostly AIs applied for control of blueberry pathogens and pests during bloom. However, for honey bees, the majority of AIs detected at each farm are not registered for use on blueberry at any time (55.2% of AIs detected), including several highly toxic insecticides. These AIs therefore came from outside the fields and farms they are expected to pollinate. For bumble bees, the majority of AIs detected in their pollen are registered for use on blueberry during bloom (56.9% of AIs detected), though far fewer AIs were sprayed at the focal farm (16.7%). Our results highlight the need for integrated farm and landscape-scale stewardship of pesticides to reduce exposure to pollinators during crop pollination. [ABSTRACT FROM AUTHOR]

WGS is used to define if isolates are "in" or "out" of an outbreak and/or microbial root cause investigation. No threshold of genetic differences is fixed and the conclusions on similarity between isolates are mainly based on the knowledge generated from previous outbreak investigations and reported mutation rates. Mutation rates in Salmonella when exposed to food processing conditions are lacking. Thus, in this study, the ability of heat and dry stress to cause genetic changes in two Salmonella serotypes frequently isolated from low moisture foods was investigated. S. enterica serovars S. Agona ATCC 51,957 and S. Mbandaka NCTC 7892 (ATCC 51,958) were repeatedly exposed to heat (90 °C for 5 min) in a low water activity and high fat matrix. No increased fitness of the strains was observed after 10 repeated heat treatments. However, genetic changes were introduced and the number of genetic differences increased with every heat treatment cycle. The genetic changes appeared randomly in the genome and were responsible for a population of diverse isolates with 0 to 28 allelic differences (0 to 38 SNPs) between them. This knowledge is key to interpret WGS results for source tracking investigations as part of a root cause analysis in a contamination event as isolates are exposed to stress conditions. [ABSTRACT FROM AUTHOR]

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity. [ABSTRACT FROM AUTHOR]

This study tested the effectiveness of HeartMan—a mobile personal health system offering decisional support for management of congestive heart failure (CHF)—on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p < 0.001), while the need for sexual counselling decreased in the control group (p < 0.05). Although the group differences were not significant, self-care increased (p < 0.05), and sexual problems decreased (p < 0.05) in the intervention group only. No significant intervention effects were observed for HRQoL, self-care confidence, illness perception and exercise capacity. Overall, results of this proof-of-concept trial suggest that the HeartMan personal health system significantly improved mental and sexual health and self-care behaviour in CHF patients. These observations were in contrast to the lack of intervention effects on HRQoL, illness perception and exercise capacity. [ABSTRACT FROM AUTHOR]

Granulovacuolar degeneration (GVD) is a common feature in Alzheimer's disease (AD). The occurrence of GVD is closely associated with that of neurofibrillary tangles (NFTs) and GVD is even considered to be a pre-NFT stage in the disease process of AD. Currently, the composition of GVD bodies, the mechanisms associated with GVD and how GVD exactly relates to NFTs is not well understood. By combining immunohistochemistry (IHC) and laser microdissection (LMD) we isolated neurons with GVD and those bearing tangles separately from human post-mortem AD hippocampus (n = 12) using their typical markers casein kinase (CK)1δ and phosphorylated tau (AT8). Control neurons were isolated from cognitively healthy cases (n = 12). 3000 neurons per sample were used for proteome analysis by label free LC–MS/MS. In total 2596 proteins were quantified across samples and a significant change in abundance of 115 proteins in GVD and 197 in tangle bearing neurons was observed compared to control neurons. With IHC the presence of PPIA, TOMM34, HSP70, CHMP1A, TPPP and VXN was confirmed in GVD containing neurons. We found multiple proteins localizing specifically to the GVD bodies, with VXN and TOMM34 being the most prominent new protein markers for GVD bodies. In general, protein groups related to protein folding, proteasomal function, the endolysosomal pathway, microtubule and cytoskeletal related function, RNA processing and glycolysis were found to be changed in GVD neurons. In addition to these protein groups, tangle bearing neurons show a decrease in ribosomal proteins, as well as in various proteins related to protein folding. This study, for the first time, provides a comprehensive human based quantitative assessment of protein abundances in GVD and tangle bearing neurons. In line with previous functional data showing that tau pathology induces GVD, our data support the model that GVD is part of a pre-NFT stage representing a phase in which proteostasis and cellular homeostasis is disrupted. Elucidating the molecular mechanisms and cellular processes affected in GVD and its relation to the presence of tau pathology is highly relevant for the identification of new drug targets for therapy. [ABSTRACT FROM AUTHOR]

Drawing on Austin's speech act theory and on related theories of performativity and positioning, this article analyses the public confessions during the 1990s by three prominent state actors in Turkey about their direct involvement in state crimes against Kurds and left-wing political opponents. All three cases received significant media attention at the time. The aim of the article is not only to shed new light on those specific confessions by the perpetrators within the Turkish context, but also to develop further theoretical insights into the phenomenon of public confessions as such. Whilst confessions of this kind are often welcomed and portrayed as truth-statements that are cathartic and enable society to move forward, this analysis demonstrates that the reality is often more complex as the confessions in question tend to go hand in hand with a disavowal of individual responsibility by the perpetrators involved. [ABSTRACT FROM AUTHOR]

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Purpose: To compare intraosseous access with peripheral venous access on adults out-of-hospital cardiac arrest (OHCA) patients' clinical outcomes. Methods: A national retrospective multicentre study was conducted based on the French National Cardiac Arrest Registry. Comparison of patients (intraosseous vs. peripheral venous access) was conducted before and after a matching using a propensity score. The propensity score included confounding factors: age, time between the call (T0) to epinephrine (to take account of how quickly vascular access was achieved), the aetiology of OHCA, the shock and the patient initial rhythm at MMT arrival. Results: A total of 1576 patients received intraosseous access, and 27,280 received peripheral intravenous access. Before matching, OHCA patients with intraosseous access were less likely to survive at all stages (return of spontaneous circulation (ROSC), 0-day survival and 30-day survival). No significant difference in neurological outcome was observed. After propensity score matching, no significant differences in 30-day survival rates (OR = 0.763 [0.473;1.231]) and neurological outcome (OR = 1.296 [0.973;1.726]) were observed. However, intraosseous patients still showed lower likelihood of short-term survival (ROSC and 0-day survival) even after propensity score matching was implemented. Conclusion: The populations we investigated were similar to those of other studies suggesting that intraosseous access is associated with reduced survival and poorer neurological outcome. Our findings suggest that intraosseous access is a comparably effective alternative to peripheral intravenous access for treating OHCA patients on matched populations. [ABSTRACT FROM AUTHOR]

Purpose: Application of radioactive tracers for sentinel lymph node biopsy (SLNB) in vulvar cancer has been established, however, the use of radioisotopes is expensive and requires complex logistics. This exploratory study evaluated the feasibility of near-infrared fluorescence-based SLNB in comparison to the gold standard using radioactive guidance.Methods: At Evangelische Kliniken Essen-Mitte (Essen, Germany) between 02/2015 and 04/2019, 33 patients with squamous cell vulvar cancer and unifocal tumors (32 midline, 1 lateral) smaller than 4 cm underwent SLNB as part of their routine primary surgical therapy. Radiolabeled nanocolloid technetium 99 (99mTc) was injected preoperatively and indocyanine green (ICG) intraoperatively. Demographic and clinical data were retrieved from patients' records, and descriptive statistics were applied. The detection rate of the ICG fluorescence technique was compared with the standard radioactive approach.Results: In patients with midline tumors, bilateral SLNB was attempted. SLNB was feasible in 61/64 (95.3%) groins with 99mTc and in 56/64 (87.5%) with ICG. In total, 125 SLNs were excised; all SLNs were radioactive and 117 (93.6%) also fluorescent. In 8 patients with BMI > 30 kg/m2, SLNB was successful in 14/15 groins (93.3%) with 99mTc and 13/15 groins (86.7%) with ICG. Upon final histology, infiltrated nodes were present in 9/64 (14.1%) groins and 10/125 SLNs; one positive SLN was not detected with ICG.Conclusions: SLNB using ICG is a promising technique, however, the detection rate obtained was slightly lower than with 99mTc. The detection rate increased over time indicating that experience and training may play an important role besides further methodological refinements. [ABSTRACT FROM AUTHOR]

Purpose of Review: Uterine cancer comprises endometrial carcinoma and the uterine sarcoma. Endometrial carcinomas are the most frequent variant and have early symptoms and a solid diagnostic work up, resulting in a rather fair prognosis. However, in case of advanced stage disease and relapse, treatment options are limited and prognosis is impaired. Uterine sarcomas are rare, often lacking symptoms and no diagnostic tool for correct pre-operative diagnosis are available. Prognosis is poor. Recent Findings: Circulating biomarkers as a liquid biopsy could be beneficial as a diagnostic tool in uterine sarcomas. For both carcinomas and sarcomas, circulating biomarkers could be of use in predicting early disease recurrence. Summary: This review in endometrial carcinoma and uterine sarcoma focus on circulating biomarkers; such as proteins; circulating tumor cells; circulating tumor DNA; microRNA; and immune cells. [ABSTRACT FROM AUTHOR]

Recent taxonomical revisions based on multilocus gene sequencing have provided some clarifications to dermatophyte (Arthrodermataceae) family tree. These changes promoted us to investigate the impact of the changed nomenclature of the dermatophyte strains in the BCCM/IHEM fungal collection, which contains strains of all dermatophyte genera except for Ctenomyces. For 688 strains from this collection, both internal transcribed spacer region (ITS) and partial β-tubulin (BT) sequences were aligned and a multilocus phylogenetic tree was constructed. The ITS + BT phylogentic tree was able to distinguish the genera Arthroderma, Lophophyton, Microsporum, Paraphyton, Nannizzia and Trichophyton with high certainty. Epidermophyton, which is widely considered as a well-defined genus with E. floccosum as the only representative, fell within the Nannizzia clade, whereas the phylogenetic analysis, based on the ITS region alone, differentiates Epidermophyton from Nannizzia as a separate genus. Re-identification and reclassification of many strains in the collection have had a profound impact on the composition of the BCCM/IHEM dermatophyte collection. The biggest change is the decline of prevalence of Arthroderma strains; starting with 103 strains, only 22 strains remain in the genus after reassessment. Most Arthroderma strains were reclassified into Trichophyton, with A. benhamiae and A. vanbreuseghemii leaving the genus. The amount of Microsporum strains also dropped significantly with most of these strains being reclassified into the genera Paraphyton and Nannizzia. [ABSTRACT FROM AUTHOR]

Acebutolol is a β1-selective adrenergic receptor antagonist with moderate membrane-stabilizing activity and intrinsic sympathomimetic activity; accordingly, the drug is indicated in hypertension, angina pectoris, and arrhythmia. However, acebutolol's beta-blocking properties also extend the QRS and QTc intervals, and may predispose the patient to ventricular tachydysrhythmia. Here, we report autopsy and toxicological findings on a fatal case of acebutolol self-poisoning in a 70-year-old woman. Toxicological analyses of post-mortem samples (using a liquid chromatography high-resolution mass spectrometry (LC-HR-MS) method) highlighted high concentrations of acebutolol and its metabolite diacetolol in femoral blood (92.8 mg/L and 21.2 mg/L, respectively) and other matrices (cardiac blood, urine, bile, and gastric contents). A molecular networking approach provided useful information on acebutolol's metabolism and revealed the existence of an unknown phase II metabolite of acebutolol. Molecular networking also facilitated visualization of the complex LC-HR-MS/MS datasets and the sample-to-sample comparisons that confirmed massive acebutolol intoxication by ingestion. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review provides an overview of the current clinical standard in low-grade serous ovarian cancer (LGSOC). The available evidence for surgery and standard treatments is elaborated. In addition, we discuss recent findings and novel treatments for LGSOC. Recent Findings: Two large multicenter trials studying MEK inhibitors in LGSOC have been presented in the last year. Binimetinib demonstrated an activity in LGSOC, especially in KRAS-mutated disease. Trametinib was associated with an improved progression-free survival in relapsed LGSOC. Based on the current results, MEK inhibitors could be an alternative treatment for LGSOC. Summary: Surgery is an important step in the treatment of LGSOC. Hormonal therapy and bevacizumab can be beneficial, next to chemotherapy. Targeted treatments, such as the MEK-inhibitor trametinib, seem to be efficient and should be introduced into clinical practice. [ABSTRACT FROM AUTHOR]

Inadequate or lack of prudent soil fertility management by cocoa farmers leads to nutrient depletion in cocoa production fields. The objective of this study was to assess current soil fertility status of cocoa farms from six cocoa growing regions in Ghana and to derive an integrated soil quality index (SQI). Composite soil samples from 0 to 30 cm depth were collected from 100 selected farms covering the six cocoa regions. Soil pH, %C, %N, total and available P, cation exchange capacity (CEC), and exchangeable cations (Ca, Mg, K) were measured. These parameters were analyzed using principal component analysis, normalized, and integrated into a weighted-additive SQI. Soil pH of majority (59.0%) of the farms was within 5.6–7.2, suitable for cocoa production. Available soil-P in most (82%) of the farms was < 20 mg kg−1. Soil quality in most farms was generally low, with an average SQI of 0.41 ± 0.14. Soil quality in Western region farms was relatively high, followed by farms in Brong Ahafo and Volta regions. Farms in Eastern, Central and Ashanti regions had the least soil quality. Soil pH, CEC and available P showed great influence on SQI. Given the latter observation, diagnostic yield response experiments should be conducted, which include: application of locally generated liming materials, organic residues and agro-mineral base fertilizers such as phosphate rock and dolomite. [ABSTRACT FROM AUTHOR]

Honey bees foraging on and around maize may be exposed to a number of pesticides, including neonicotinoids, but this exposure has not been well quantified in heterogeneous landscapes. Such landscapes may provide alternative foraging resources that add to or buffer pesticide risk. We assessed the influence of landscape context and maize pollen collection on pesticide levels during maize flowering. We quantified pesticides in (1) bee bread from 49 hives across New York and (2) pollen trapped weekly in one yard. Landscape composition and percent maize pollen were not related to pesticide levels. Furthermore, pesticide risk was low (< 1% contact LD50) in all but one of the pollen samples, and maize pollen was absent in the majority of samples. Our results suggest that hives near maize fields during maize flowering are not necessarily exposed to high levels of neonicotinoids and other pesticides in pollen, especially if uncontaminated pollen sources exist nearby. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this systematic review is to provide an overview of the efficacy of different exercise interventions to counter sarcopenia in older adults. This review will allow the Belgian Society of Gerontology and Geriatrics and other scientific societies to formulate specific exercise recommendations in their Clinical Guidelines for Sarcopenia. Design: We used the method of a systematic umbrella-review. Based on the level of evidence, we formulated specific recommendations for clinical practice. Methods: Two databases (Pubmed and Web Of Science) were searched systematically and methodological quality of the reviews was assessed. Extracted data was than mapped to an exercise category and an overall synthesis (bottom line statements) was formulated for each of these exercise categories. Subsequently, we assigned a rating of the quality of the evidence supporting each bottom line statement. Results: We identified 14 systematic reviews or meta-analyses, encompassing four exercise categories: resistance training, resistance training + nutritional supplementation, multimodal exercise programmes and bloodflow restriction training. Importantly, very few systematic reviews or meta-analyses clearly mentioned baseline sarcopenia status. There is high quality evidence for a positive and significant effect of resistance training on muscle mass, muscle strength, and physical performance. The added effect of nutritional supplementation for resistance training on muscle function appears limited. Blood flow restriction training is a novel training method that has a significant impact on muscle strength. Conclusion: Since sarcopenia is affecting all skeletal muscles in the body, we recommend training the large muscle groups in a total body approach. Although low-intensity resistance training (≤50% 1RM) is sufficient to induce strength gains, we recommend a high-intensity resistance training program (i.e. 80% 1RM) to obtain maximal strength gains. Multimodal exercises and blood flow restriction resistance training may be considered as well. [ABSTRACT FROM AUTHOR]

This study estimates the stigma effect of unemployment and overeducation within one framework. We conduct a randomised field experiment in which we send out trios of fictitious job applications, from male candidates with no relevant work experience, to real vacancies. One candidate graduated just a few months before the application, the two others graduated a year earlier and had been unemployed or underemployed since that time. By monitoring the subsequent callback, we find evidence of a larger stigma effect of unemployment than overeducation. The stigma effect of overeducation is found to occur for permanent contract jobs but not for temporary ones. [ABSTRACT FROM AUTHOR]

Natural gas as a fuel for heavy duty applications has advantages in terms of lower CO2 and PM compared to Diesel applications. This makes operating heavy duty applications on natural gas attractive. However, in terms of aftertreatment, the challenge becomes one of controlling methane emissions over a range of vehicle operating conditions. Methane light off occurs > 400 °C and requires highly loaded precious metal catalysts (Raj in Johnson Matthey Technol Rev 60:228-235, 2016). This temperature is manageable in stoichiometric applications. However, for lean operating applications, the exhaust temperature can be below this posing a significant challenge for CH4 control. When operating lean the NOx emissions also become a challenge hence the requirement for a dedicated NOx control system. As part of the EU funded HD GAS project, an aftertreatment system was developed to meet the challenges of both NOx and CH4 control for a lean operating natural gas heavy duty engine. Fundamental studies were performed by the academic partners focusing on CH4 and NOx control, with the implementation and calibration on the engine performed by the industrial partners. This paper will discuss the steps taken from fundamental catalyst characterisation and catalyst specification to full size catalyst implementation onto a newly developed natural gas engine in order to meet Euro VI emissions legislation. [ABSTRACT FROM AUTHOR]