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Ricin is a highly toxic protein, capable of inhibiting protein synthesis within cells, and is produced from the beans of the Ricinus communis (castor bean) plant. Numerous recent incidents involving ricin have occurred, many in the form of mailed letters resulting in both building and mail sorting facility contamination. The goal of this study was to assess the decontamination efficacy of several commercial off-the-shelf (COTS) cleaners and decontaminants (solutions of sodium hypochlorite [bleach], quaternary ammonium, sodium percarbonate, peracetic acid, and hydrogen peroxide) against a crude preparation of ricin toxin. The ricin was inoculated onto four common building materials (pine wood, drywall joint tape, countertop laminate, and industrial carpet), and the decontaminants were applied to the test coupons using a handheld sprayer. Decontamination efficacy was quantified using an in-vitro cytotoxicity assay to measure the quantity of bioactive ricin toxin extracted from test coupons as compared to the corresponding positive controls (not sprayed with decontaminant). Results showed that decontamination efficacy varied by decontaminant and substrate material, and that efficacy generally improved as the number of spray applications or contact time increased. The solutions of 0.45% peracetic acid and the 20,000-parts per million (ppm) sodium hypochlorite provided the overall best decontamination efficacy. The 0.45% peracetic acid solution achieved 97.8 to 99.8% reduction with a 30-min contact time. [ABSTRACT FROM AUTHOR]

Head porters working in markets in sub-Saharan Africa (SSA) are one of the world's most vulnerable and socioeconomically disadvantaged groups. They consist predominantly of uneducated women and girls seeking to escape poverty, early marriage, and other issues of domestic violence. Most female head porters are in their reproductive years and often lack access to sexual reproductive health services (SRHS) despite being at high risk for sexually transmitted infections (STIs), unplanned pregnancies, and gender-based violence. The low priority for women and girls' SRH in many SSA countries highlights the need to explore the factors influencing the accessibility of services for failure to do so restrains human development. An initial search of the literature was conducted and revealed no current scoping or systematic reviews on the accessibility to SRHS for female head porters in SSA. We outline a scoping review protocol, using the Joanna Briggs Institute methodology, to determine the interventions that influence the accessibility of SRHS for female head porters in SSA. The protocol is registered with Open Science Framework (https://osf.io/hjfkd). Findings will not only be valuable for female head porters but for all vulnerable female groups in SSA who experience high SRH risks and social disparities. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic confronted the medical community worldwide with numerous challenges, not only with respect to medical care, but also for teaching the next generation of physicians. To minimize the risk of infections patient-unrelated classes can be held digitally. Here we present a student initiated, web-based teaching approach, called "From symptom to diagnosis". In this seminar case reports of rare diseases were presented to the audience in a symptom-focused manner. The patients´ most significant symptoms were presented, followed by an in-depth discussion about differential diagnosis. First glance diagnosis pictures were shown to improve students´ ability to identify important clinical scenarios. We used chat functions as well as an audience response system to make the seminar more interactive. By this we attracted between 71 and 147 participants per session. The online seminar was very well perceived and 97% of the students saw an improvement of their diagnostic skills. In summary, we successfully established an interactive, web-based teaching format for medical students. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate and compare the decontamination efficacy of liquid formaldehyde solutions for three soil types (sand, loam, and clay) against spores of Bacillus anthracis (B.a.) and Bacillus atrophaeus. Approximately 1 x 108 colony forming units were inoculated into each sample. Through a series of six bench-scale experiments, two concentrations and two volumes of liquid formaldehyde solution were then added to the soil samples and allowed to remain in contact for either 24 or 48 hours. Decontamination efficacy was assessed at either 22° or 10°C with or without lids atop the sample jars. Complete inactivation (no spores recovered from the soil samples, typically providing > 7 log reduction) of B.a. occurred in all soil types in five of the six tests, while complete inactivation of B. atrophaeus was achieved in all soil types for three of the six tests. The results demonstrated a higher probability of complete inactivation of spores for samples that were covered, samples that received the higher volume of formaldehyde, and those contaminated with B.a. Overall, the use of liquid formaldehyde solution (2.5–5%) was highly effective in inactivating entire spore populations (typically > 107 CFU) for both B.a. and B. atrophaeus in the soil matrices studied. Covering the soil after application would allow for less formaldehyde solution to be used without impacting the overall efficacy of the process. The data from this study may aid in the selection of appropriate decontamination parameters when using liquid formaldehyde for soil remediation. The data may also aid in the decision to use B. atrophaeus as a surrogate for B.a. when performing further decontamination studies using liquid formalin solutions. [ABSTRACT FROM AUTHOR]

Information technology (IT) capability is an organizational capability that enables organizations to acquire, deploy, combine, and reconfigure IT resources. As such, it is often investigated in conjunction with organizational agility—an organization's ability to sense and respond to changes—and organizational performance. Studies on IT capability distinguish between reactive and proactive IT capability and identify varying effects in relation to agility and performance. While reactive IT capability supports and enhances work processes, proactive IT capability supports and enhances business strategies. In the light of the mixed results of prior research, we conduct a meta-analytical investigation into the varying effects that reactive and proactive IT capability have on organizational agility and organizational performance. We identified 6.436 studies from multiple sources that we systematically reduced to include 72 empirical studies in our analysis. Contrary to previous results and widely held opinion, our meta-analysis neither finds support for differences in effect size between reactive (r+ = 0.39, k = 34, 95% Confidence Interval (CI) [0.34, 0.44]) and proactive IT capability (r+ = 0.38, k = 21, 95% CI [0.31, 0.45]) toward agility (z = 0.68, p = 0.25), nor from reactive IT capability (r+ = 0.31, k = 43, 95% CI [0.26, 0.37]) and proactive IT capability (r+ = 0.33, k = 25, 95% CI [0.27, 0.40]) toward performance (z = 1.11, p = 0.13). Given the importance of IT capability, we discuss possible explanations and propose four areas for future research: latency, sequence, configurational, and theoretical multiplicity of IT capability. [ABSTRACT FROM AUTHOR]

Background: The selection of the appropriate species is one of the key issues in experimental medicine. Bile duct ligation is the mostly used experimental model in rodents to explore special aspects of occlusive cholestasis. We aimed to clarify if rats or mice are suitable for the same or different aspects in cholestasis research. Methods: We induced biliary occlusion by ligation and transection of the common bile duct (tBDT) in rats and mice (each n = 25). Recovery from surgical stress was assessed by daily scoring (stress score, body weight). At five different time points (days 1, 3, 7, 14, 28 after tBDT) we investigated hepatic morphometric and architectural alterations (Haematoxylin-Eosin staining, Elastica van Gieson staining) and the proliferative activities of parenchyma cells (Bromodeoxyuridine staining); as well as established systemic markers for liver synthesis, hepatocellular damage and renal dysfunction. Results: We found substantial differences regarding survival (rats: 100%, 25/25 vs. mice 92%, 22/25, p = 0.07) and body weight gain (p<0.05 at postoperative days 14 and 28 (POD)). Rats showed a faster and progressive hepatobiliary remodelling than mice (p<0.05 at POD 7+14+28), resulting in: i) stronger relative loss of hepatocellular mass (rats by 31% vs. mice by 15% until POD 28; p<0.05 at POD 7+14+28); ii) rapidly progressing liver fibrosis (p<0.05 at POD 14); iii) a faster and stronger proliferative response of parenchyma cells (hepatocytes: p<0.05 at POD 1+14+18; cholangiocytes: p<0.05 at POD 1+3+7+28); and iv) only tiny bile infarcts compared to mice (p<0.05 at POD 1+3+7+14). Both species showed comparable elevated markers of hepatocellular damage and serum bilirubin. Conclusion: The key difference between rats and mice are the severity and dynamics of histological alterations, possibly accounting for their different susceptibilities for (septic) complications with low survival (mice). [ABSTRACT FROM AUTHOR]

Many pathologies can occur in the periportal space and manifest as fluid accumulation, visible in Computed tomography (CT) images as a circumferential region of low attenuation around the intrahepatic portal vessels, called periportal halo (PPH). This finding is associated with different types of hepatic and extra-hepatic disease in humans and remains a non-specific sign of unknown significance in veterinary literature. The aim of this study was to investigate the prevalence of PPH in a population of patients undergoing CT examination and to assess the presence of lesions related to hepatic and extra-hepatic disease in presence of PPH. CT studies including the cranial abdomen of dogs and cats performed over a 5-year period were retrospectively reviewed. The prevalence of PPH was 15% in dogs and 1% in cats. 143 animals were included and the halo was classified as mild, moderate and severe, respectively in 51%, 34% and 15% of animals. The halo distribution was generalized in 79 cases, localized along the second generation of portal branches in 63, and along the first generation only in one. Hepatic disease was present in 58/143 and extra-hepatic disease in 110/143 of the cases. Main cause of hepatic (36%) and extra-hepatic disease (68%) was neoplasia. Associations between halo grades and neoplasia revealed to be not statistically significant (p = 0.057). In 7% of animals the CT examination was otherwise unremarkable. PPH is a non-specific finding, occurring in presence of a variety of diseases in the examined patient population. [ABSTRACT FROM AUTHOR]

In early-onset generalized torsion dystonia, caused by a GAG deletion in TOR1A (DYT1), enhanced striatal cholinergic activity has been suggested to be critically involved. Previous studies have shown increased acetylcholine levels in the striatum of DYT1 knock-in (KI) mice. Ex vivo data indicated that muscarinic receptor antagonists normalize the activity of striatal cholinergic interneurons. Currently receptor subtype specific antagonists are developed for therapy, however, it is yet unknown whether the levels of targeted receptors are unaltered. In the present study, we firstly examined the expression of M1 and M4 receptors in DYT1 KI mice in comparison to wildtype mice. While no changes in mRNA were found in the motor cortex, the expression of M1 was higher in the striatum of DYT1 KI. However, M1 protein did not differ in striatum and cortex between the animal groups as shown by immunohistochemistry and western blot. M4 receptor protein, unaltered in the cortex, was slightly lower in lateral subparts of the striatum, but unchanged in somata of cholinergic interneurons and substance P immunoreactive projection neurons. Functional alterations of the cholinergic system and of aberrant striatal plasticity, demonstrated by previous studies, seem not to be related to overt changes in M1 and M4 expression. This critically informs the ongoing development of respective antagonists for therapy of dystonia. [ABSTRACT FROM AUTHOR]

Whole genome sequencing of viral specimens following molecular diagnosis is a powerful analytical tool of molecular epidemiology that can critically assist in resolving chains of transmission, identifying of new variants or assessing pathogen evolution and allows a real-time view into the dynamics of a pandemic. In Cyprus, the first two cases of COVID-19 were identified on March 9, 2020 and since then 33,567 confirmed cases and 230 deaths were documented. In this study, viral whole genome sequencing was performed on 133 SARS-CoV-2 positive samples collected between March 2020 and January 2021. Phylogenetic analysis was conducted to evaluate the genomic diversity of circulating SARS-CoV-2 lineages in Cyprus. 15 different lineages were identified that clustered into three groups associated with the spring, summer and autumn/winter wave of SARS-CoV-2 incidence in Cyprus, respectively. The majority of the Cypriot samples belonged to the B.1.258 lineage first detected in September that spread rapidly and largely dominated the autumn/winter wave with a peak prevalence of 86% during the months of November and December. The B.1.1.7 UK variant (VOC-202012/01) was identified for the first time at the end of December and spread rapidly reaching 37% prevalence within one month. Overall, we describe the changing pattern of circulating SARS-CoV-2 lineages in Cyprus since the beginning of the pandemic until the end of January 2021. These findings highlight the role of importation of new variants through travel towards the emergence of successive waves of incidence in Cyprus and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures. [ABSTRACT FROM AUTHOR]

Stable personality dispositions, like motives, are often assumed to exert a direct, stable impact on behavior. This also applies to the explicit achievement motive, which is supposed to influence the behavior that individuals select and how strongly they engage in it. Drawing on motivational intensity theory, we demonstrated in two studies that explicit achievement motive strength only predicted exerted force in a hand grip task if task difficulty was unclear. If task difficulty was clear, explicit achievement motive strength did not influence exerted force. Our findings suggest that the availability of information about the difficulty of motive satisfaction moderates the impact of the explicit achievement motive on behavior. [ABSTRACT FROM AUTHOR]

Assessing past foodways, subsistence strategies, and environments depends on the accurate identification of animals in the archaeological record. The high rates of fragmentation and often poor preservation of animal bones at many archaeological sites across sub-Saharan Africa have rendered archaeofaunal specimens unidentifiable beyond broad categories, such as "large mammal" or "medium bovid". Identification of archaeofaunal specimens through Zooarchaeology by Mass Spectrometry (ZooMS), or peptide mass fingerprinting of bone collagen, offers an avenue for identification of morphologically ambiguous or unidentifiable bone fragments from such assemblages. However, application of ZooMS analysis has been hindered by a lack of complete reference peptide markers for African taxa, particularly bovids. Here we present the complete set of confirmed ZooMS peptide markers for members of all African bovid tribes. We also identify two novel peptide markers that can be used to further distinguish between bovid groups. We demonstrate that nearly all African bovid subfamilies are distinguishable using ZooMS methods, and some differences exist between tribes or sub-tribes, as is the case for Bovina (cattle) vs. Bubalina (African buffalo) within the subfamily Bovinae. We use ZooMS analysis to identify specimens from extremely fragmented faunal assemblages from six Late Holocene archaeological sites in Zambia. ZooMS-based identifications reveal greater taxonomic richness than analyses based solely on morphology, and these new identifications illuminate Iron Age subsistence economies c. 2200–500 cal BP. While the Iron Age in Zambia is associated with the transition from hunting and foraging to the development of farming and herding, our results demonstrate the continued reliance on wild bovids among Iron Age communities in central and southwestern Zambia Iron Age and herding focused primarily on cattle. We also outline further potential applications of ZooMS in African archaeology. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to retrospectively assess the effect of Radiofrequency Volumetric Tissue Reduction (RFVTR) on hypertrophic turbinates and clinical outcome in brachycephalic dogs when included in multi-level surgery (MLS). Study design: Clinical retrospective multicenter study. Animals: 132 client-owned brachycephalic dogs. Methods: 132 brachycephalic dogs with high-grade Brachycephalic Obstructive Airway Ayndrome (BOAS) and hypertrophic turbinates were treated with RFVTR as part of MLS of the upper airways. Intranasal obstruction was evaluated by computer tomography (CT) and antero-/retrograde rhinoscopy before and 6 months after RFVTR. The clinical records, the CT images and the rhinoscopy videos were reviewed and clinical evolution was evaluated using a standardized questionnaire. The data was scored semi-quantitatively. Results: In this study, 132 patients were included for a follow-up period of 120 weeks. RFVTR resulted in minor complications, including serous nasal discharge within the first postoperative week in all dogs, and intermittent nasal congestion between 3–8 weeks after treatment in 24.3% of the patients. Rhinoscopy and CT follow-ups were available for 33 patients. Six months after treatment intranasal airspace was increased (p = 0.002) and the presence and overall amount of mucosal contact points was reduced (p = 0.039). Conclusion: MLS with RFVTR led to a significant reduction in turbinate volume at the 6-month follow-up examination and significant clinical improvement over a long-term period of 120 weeks. This suggests the viability of RFVTR as a turbinate-preserving treatment for intranasal obstruction in dogs with BOAS. Clinical significance: RFVTR is a minimally invasive turbinoplasty technique for intranasal obstruction in dogs with BOAS and can be included in MLS without increasing complication rates. [ABSTRACT FROM AUTHOR]

Self-esteem has been shown to be both predictive of and predicted by characteristics of romantic relationships. While there is an increasing number of studies yielding support for reciprocal influences between self-esteem and perceived conflict in romantic relationships, longitudinal transactions between these constructs from both partners' perspectives have not been studied systematically to date. Our aim was to close this gap. To that end, we examined the transactional and longitudinal interplay between self-esteem and perceived relationship conflict in continuing romantic couples from a dyadic perspective. Our sample consisted of N = 1,093 young adult female–male relationships from the German Family Panel. Individuals' self-esteem, perceived conflict frequency, and their perceptions of their partners' dysfunctional conflict styles (i.e., unconstructive behavior, withdrawal) were examined annually throughout a time span of five years. Based on dyadic bivariate latent change models, we tested our assumption that self-esteem and aspects of perceived relationship conflict are negatively interrelated within individuals and between partners both within and across time. We found one actor effect of self-esteem on changes in unconstructive behavior above and beyond initial unconstructive behavior levels, supporting self-broadcasting perspectives. Moreover, we found strong support for sociometer perspectives. Actor effects highlighted the importance of perceived conflict frequency for subsequent self-esteem changes. In addition, perceived conflict styles affected both partners' self-esteem. The results imply that perceiving conflict is a between-person process, and might be more important for the development of self-esteem than vice versa. [ABSTRACT FROM AUTHOR]

Metabolites play a key role in plants as they are routing plant developmental processes and are involved in biotic and abiotic stress responses. Their analysis can offer important information on the underlying processes. Regarding plant breeding, metabolite concentrations can be used as biomarkers instead of or in addition to genetic markers to predict important phenotypic traits (metabolic prediction). In this study, we applied a genome-wide association study (GWAS) in a wild barley nested association mapping (NAM) population to identify metabolic quantitative trait loci (mQTL). A set of approximately 130 metabolites, measured at early and late sampling dates, was analysed. For four metabolites from the early and six metabolites from the late sampling date significant mQTL (grouped as 19 mQTL for the early and 25 mQTL for the late sampling date) were found. Interestingly, all of those metabolites could be classified as sugars. Sugars are known to be involved in signalling, plant growth and plant development. Sugar-related genes, encoding mainly sugar transporters, have been identified as candidate genes for most of the mQTL. Moreover, several of them co-localized with known flowering time genes like Ppd-H1, HvELF3, Vrn-H1, Vrn-H2 and Vrn-H3, hinting on the known role of sugars in flowering. Furthermore, numerous disease resistance-related genes were detected, pointing to the signalling function of sugars in plant resistance. An mQTL on chromosome 1H in the region of 13 Mbp to 20 Mbp stood out, that alone explained up to 65% of the phenotypic variation of a single metabolite. Analysis of family-specific effects within the diverse NAM population showed the available natural genetic variation regarding sugar metabolites due to different wild alleles. The study represents a step towards a better understanding of the genetic components of metabolite accumulation, especially sugars, thereby linking them to biological functions in barley. [ABSTRACT FROM AUTHOR]

The interpretation of medical images is an error-prone process that may yield severe consequences for patients. In dental medicine panoramic radiography (OPT) is a frequently used diagnostic procedure. OPTs typically contain multiple, diverse anomalies within one image making the diagnostic process very demanding, rendering students' development of visual expertise a complex task. Radiograph interpretation is typically taught through massed practice; however, it is not known how effective this approach is nor how it changes students' visual inspection of radiographs. Therefore, this study investigated how massed practice–an instructional method that entails massed learning of one type of material–affects processing of OPTs and the development of diagnostic performance. From 2017 to 2018, 47 dental students in their first clinical semester diagnosed 10 OPTs before and after their regular massed practice training, which is embedded in their curriculum. The OPTs contained between 3 to 26 to-be-identified anomalies. During massed practice they diagnosed 100 dental radiographs without receiving corrective feedback. The authors recorded students' eye movements and assessed the number of correctly identified and falsely marked low- and high prevalence anomalies before and after massed practice. Massed practice had a positive effect on detecting anomalies especially with low prevalence (p <.001). After massed practice students covered a larger proportion of the OPTs (p <.001), which was positively related to the detection of low-prevalence anomalies (p =.04). Students also focused longer, more frequently, and earlier on low-prevalence anomalies after massed practice (ps <.001). While massed practice improved visual expertise in dental students with limited prior knowledge, there is still substantial room for improvement. The results suggest integrating massed practice with more deliberate practice, where, for example, corrective feedback is provided, and support is adapted to students' needs. [ABSTRACT FROM AUTHOR]

Hepatic fat fraction (HFF) can be non-invasively estimated with magnetic resonance imaging (MRI) multiple echo gradient recalled echo (GRE) sequence. The aim of this study was to test different methods of sampling strategies to quantify the HFF in healthy cats during body weight gain. Twelve healthy adult male cats were examined in a 3 Tesla MRI unit. Sequences included morphological images, and multiple echo GRE sequence. Cats were scanned at the beginning of the study and twice, each 20 weeks apart during body weight gain. HFF was calculated with 5 different methods of sampling on the multiple echo GRE sequence with different number, size and position of regions of interest (ROIs) and by 2 operators. Results indicated that HFF increased with increasing body weight, and the increase was appreciated with all the 5 methods. There was overall excellent agreement (interclass correlation coefficient = 0.820 (95% confidence interval:0.775–0.856)) between the 2 operators. HFF in the left lateral hepatic lobe was lower than in the other analyzed lobes. HFF measured on large free-hand drawn ROIs was higher than HFF measured with smaller ROIs size. This study proves that different sampling methods for quantification of HFF on multiple echo GRE sequence have overall excellent repeatability and ability to appreciate increased HFF. [ABSTRACT FROM AUTHOR]

Our field data from the Upper Palaeolithic site of Al-Ansab 1 (Jordan) and from a pollen sequence in the Dead Sea elucidate the role that changing Steppe landscapes played in facilitating anatomically modern human populations to enter a major expansion and consolidation phase, known as the „Early Ahmarian", several millennia subsequent to their initial Marine Isotope Stage 4/3 migration from Africa, into the Middle East. The Early Ahmarian techno-cultural unit covers a time range between 45 ka–37 ka BP. With so far more than 50 sites found, the Early Ahmarian is the first fully Upper Palaeolithic techno-cultural unit exclusively and undisputedly related to anatomically modern human populations. In order to better understand the potentially attractive features of the Early Ahmarian environmental context that supported its persistence for over 8,000 years, we carried out a decennial research program in Jordan and in the Dead Sea. This included (1) a geoscientific and archaeological survey program in the Wadi Sabra (Jordan) with a particular focus on excavations at the Early Ahmarian site of Al-Ansab 1 alongside the detailed analysis of Quaternary sediments from the same area and (2) palaeobotanical research based on Quaternary lake deposits from the Dead Sea. Our pollen data from the Dead Sea indicate slow, low frequency vegetational variation with expanding Artemisia steppe, from 60 to 20 ka BP (MIS 3–2). Here, we see a reciprocal assimilation of southern and northern Levantine vegetation zones thereby enhancing a long-lasting south-to-north steppe corridor. The same integration process accelerated about 40 ka ago, when forested areas retreated in the Lebanese Mountains. The process then extended to encompass an area from Southern Lebanon to the Sinai Peninsula. We argue that, at the same time, the carriers of the Early Ahmarian techno-cultural unit extended their habitat from their original Mediterranean biome (in the North) to the Saharo-Arabian biome (to the South). Our excavation of Al-Ansab 1, a campsite at the eastern margins of the Early Ahmarian settlement area, indicates far reaching annual movements of small, highly mobile hunter-gatherer groups. We assume a low degree of settlement complexity, still allowing for habitat extension of the Early Ahmarian into the margins of the Levantine corridor. Due to our radiometric dates, our combined archaeological and environmental record sheds light on an evolved phase of the Early Ahmarian, around 38 ka ago, rather than the starting phase of this techno-cultural unit. Possible application of our model to the starting phase of the Early Ahmarian remains an aspect of future research. [ABSTRACT FROM AUTHOR]

Background: Risk communication, situated in the model of shared decision making (SDM), is an essential element in daily clinical practice. The scientific literature makes a number of generic recommendations. Yet the application of risk communication remains a challenge in patient-clinician encounters. How clinicians actually communicate risk during consultations is not well understood. We aimed to explore the risk communication strategies used by clinicians and extract narratives and visualizations of those strategies to help inform medical education. Methods: In this qualitative descriptive study, we interviewed fifteen purposely sampled clinicians from several medical disciplines, who were familiar with the concept of SDM. Deductive and inductive content analysis was used during an iterative data collection and analyses process. Results: Our study identified various strategies reported to be used by clinicians to address the complexities of risk communication such as dealing with uncertainty. These included verbal, numerical and visual risk communication and framing. Clinicians were familiar with recommended risk formats such as natural frequencies and population pictograms. However, it became clear that clinicians' expertise and communication goals also play an important role in the risk talk. Clinicians try to lay a foundation for balanced decision-making and to incorporate patient preferences while faced with several challenges such as the dilemma of raising awareness but triggering anxiety or fan fear in patients. Consequently, they also use communication goals such as influencing mindset and reassuring patients. Additionally, clinicians frequently have to account for the illusion of certainty in the risk talk. Conclusion: Risk communication is a multi-faceted construct that cannot be dealt with in isolation from the clinical context. For future research we recommend considering a more practical framework within the clinical setting and to take a goal-directed approach into account when investigating and teaching the topic. The patient perspective should also be addressed in further research. [ABSTRACT FROM AUTHOR]

Like other crop species, barley, the fourth most important crop worldwide, suffers from the genetic bottleneck effect, where further improvements in performance through classical breeding methods become difficult. Therefore, indirect selection methods are of great interest. Here, genomic prediction (GP) based on 33,005 SNP markers and, alternatively, metabolic prediction (MP) based on 128 metabolites with sampling at two different time points in one year, were applied to predict multi-year agronomic traits in the nested association mapping (NAM) population HEB-25. We found prediction abilities of up to 0.93 for plant height with SNP markers and of up to 0.61 for flowering time with metabolites. Interestingly, prediction abilities in GP increased after reducing the number of incorporated SNP markers. The estimated effects of GP and MP were highly concordant, indicating MP as an interesting alternative to GP, being able to reflect a stable genotype-specific metabolite profile. In MP, sampling at an early developmental stage outperformed sampling at a later stage. The results confirm the value of GP for future breeding. With MP, an interesting alternative was also applied successfully. However, based on our results, usage of MP alone cannot be recommended in barley. Nevertheless, MP can assist in unravelling physiological pathways for the expression of agronomically important traits. [ABSTRACT FROM AUTHOR]

Background: Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background. Method: Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively. Results: Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study. Conclusion: Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of a linear gadolinium-based contrast agent (GBCA) on the signal intensity (SI) of the deep cerebellar nuclei (DCN) in a retrospective clinical study on dogs after multiple magnetic resonance (MR) examinations with intravenous injections of gadodiamide and LA-ICP-MS analysis of a canine cerebellum after gadodiamide administration. Animals: 15 client-owned dogs of different breeds and additionally 1 research beagle dog cadaver. Procedures: In the retrospective study part, 15 dogs who underwent multiple consecutive MR imaging examinations with intravenous injection of linear GBCA gadodiamide were analyzed. SI ratio differences on unenhanced T1-weighted MR images before and after gadodiamide injections was calculated by subtracting SI ratios between DCN and pons of the first examination from the ratio of the last examination. Additionally, 1 research beagle dog cadaver was used for LA-ICP-MS (Laser ablation inductively coupled plasma mass spectrometry) analysis of gadolinium in the cerebellum as an add-on to another animal study. Descriptive and non-parametrical statistical analysis was performed and a p-value of < 0.05 was considered significant. Results: No statistically significant differences of SI ratios, between DCN and pons, were detectable based on unenhanced T1-weighted MR images. LA-ICP-MS analyses showed between 1.5 to 2.5 μg gadolinium/g tissue in the cerebellum of the examined dog, 35 months after the last of 3 MRI examination with gadodiamide (two examinations at a dose of 1 x 0.1mmol/kg, last examination at a dose of 3 x 0.05mmol/kg). Conclusion and clinical relevance: Although the retrospective MRI study did not indicate any visible effect of SI increase after multiple gadodiamide exposures, further studies based on LA-ICP-MS showed that the optical threshold was not reached for a potential visible effect. Gadolinium was detectable at a level of 1.5 to 2.5 μg gadolinium/g tissue by using LA-ICP-MS in the cerebellum 35 months after last MRI examination. The general importance of gadolinium retention of subvisible contents requires further investigation. [ABSTRACT FROM AUTHOR]

Enteroviruses (EVs) are associated with a broad spectrum of disease manifestations, including aseptic meningitis, encephalitis, hand, foot and mouth disease, acute flaccid paralysis and acute flaccid myelitis with outbreaks being reported frequently world-wide. The aim of this study was the molecular characterization of all enteroviruses detected in Cyprus in the ten-year period from January 2008 and December 2017 as well as a description of the circulation patterns associated with the most frequently encountered genotypes. For this purpose, serum, cerebrospinal fluid, nasal swab, skin swab and/or stool samples from 2666 patients with a suspected EV infection were analysed between January 2008 and December 2017. Enteroviruses were detected in 295 (11.1%) patients, which were then investigated further for epidemiological analysis by VP1 genotyping. Overall, 24 different enterovirus types belonging to three different species were identified. The predominant species was EV-B (209/295, 71%), followed by species EV-A (77/295, 26.1%). Only one virus belonged to species EV-D, whereas EV-C enteroviruses were not identified at all. The most frequent genotypes identified were echovirus 30 (26.1%), echovirus 6 (14.2%) and coxsackievirus A6 (10.9%). While Echovirus 30 and echovirus 6 frequency was significantly higher in patients older than 3 years of age, the opposite was observed for CV-A16 and EV-A71, which dominated in young children less than 3 years. Importantly, for the current study period a significant increase of previously only sporadically observed EV-A types, such as EV-A71 and CV-A16 was noted. A phylogenetic analysis of EV-A71 showed that the majority of the EV-A71 strains from Cyprus belonged to sub-genogroup C1 and C2, with the exception of one C4 strain that was observed in 2011. The data presented provide a comprehensive picture of enteroviruses circulating in Cyprus over the last decade and will be helpful to clinicians and researchers involved in the treatment, prevention and control of enteroviral infections by helping interpret trends in enteroviral diseases by associating them with circulating serotypes, for studying the association of enteroviruses with clinical manifestations and develop strategies for designing future EV vaccines. [ABSTRACT FROM AUTHOR]

Motion analysis systems are widely employed to identify movement deficiencies—e.g. patterns that potentially increase the risk of injury or inhibit performance. However, findings across studies are often conflicting in respect to what a movement deficiency is or the magnitude of association to a specific injury. This study tests the information content within movement data using a data driven framework that was taught to classify movement data into the classes: NORM, ACLOP and ACLNO OP, without the input of expert knowledge. The NORM class was presented by 62 subjects (124 NORM limbs), while 156 subjects with ACL reconstruction represented the ACLOP and ACLNO OP class (156 limbs each class). Movement data from jumping, hopping and change of direction exercises were examined, using a variety of machine learning techniques. A stratified shuffle split cross-validation was used to obtain a measure of expected accuracy for each step within the analysis. Classification accuracies (from best performing classifiers) ranged from 52 to 81%, using up to 5 features. The exercise with the highest classification accuracy was the double leg drop jump (DLDJ; 81%), the highest classification accuracy when considering only the NORM class was observed in the single leg hop (81%), while the DLDJ demonstrated the highest classification accuracy when considering only for the ACLOP and ACLNO OP class (84%). These classification accuracies demonstrate that biomechanical data contains valuable information and that it is possible to differentiate normal from rehabilitating movement patterns. Further, findings highlight that a few features contain most of the information, that it is important to seek to understand what a classification model has learned, that symmetry measures are important, that exercises capture different qualities and that not all subjects within a normative cohort utilise ‘true’ normative movement patterns (only 27 to 71%). [ABSTRACT FROM AUTHOR]

Background: Manual skull drilling is an old but in modern neurosurgery still established procedure which can be applied quickly and universally in emergency situations. Electrical drilling requires more complex equipment and is usually reserved to the Operating Room (OR). It also seems desirable to apply an electrical drill for bedside usage but a suitable product does not exist so far. Method: Our experimental study using a manually and an electrically driven skull drill included a total of 40 holes drilled into synthetic biomechanical sheets. Half of the holes were produced with a prototype electrical drilling machine of the company Kaiser Technology and half of them with a traditional manual drill. Different drilling parameters such as the geometry of the borehole, the drilling forces and the drilling vibrations were captured during all experiments. Results: The electrical drilling needed higher vertical force by the operators and a longer time to penetrate the sheet. A reason was the relatively lower rotational speed provided by this particular drill. When drilling electrically the vibrations were substantially less which in turn led to a more precise shape of the holes (revealed by observation via a microscope). Conclusions: The electrification of bedside drilling can in principle enable emergency craniostomies to be performed with greater ease and accuracy. The power of the electric drive, however, must be at least equivalent to the power of the traditional manual drill. Otherwise, the vertical forces exerted on the scull by the operator become inhibitive. The challenge is to combine cost-efficiency and re-sterilizability of an electrically driven drilling machine which at the same time is small and simple enough to qualify for emergency applications. [ABSTRACT FROM AUTHOR]

Background: In February 2012 the ten-valent pneumococcal conjugate vaccine (PCV10) with a 2+1 doses schedule (3, 5, 12 or 14 months of age) without catch-up vaccination was introduced in Austria. We assessed direct and indirect vaccine effects on invasive pneumococcal disease (IPD) by a population-based intervention study. Methods: The study period was divided into pre- (2009–2011) and post-period (2013–2017, February), regarding 2012 as transition year. Outcomes were defined as PCV10 ST-IPD, the PCV10-related ST 6A and 19A IPD and non-PCV10 excluding ST 6A-/19A-IPD (NVT-IPD). We used national surveillance data and compared average monthly incidence rate (IR) between pre- and post-period among <5, 5–49 and ≥50 years old. Additionally, for the 5–49 and ≥50 years old, and the 50–59 and ≥60 years old, we analyzed monthly incidence data of the pre-, post-period, and estimated trend and level changes by using a segmented time-series regression. Results: The PCV-10 IPD was reduced by 58% (95% CI: 30%; 74%) and 67% (95% CI: 32%; 84%) among <5 and ≥50 years old; the reduction in ≥60 years was 71% (95% CI: 36%; 88%). There were no significant changes in the pre-post-rate or incidence trend of NVT-IPD in the <5 and ≥50 years old. ST-specific analyses revealed no ST 6A- and ST 19A IPD decline in any age-group, and a ST 8 IPD increase among ≥50 years old (IR ratio: 3.5; 95% CI: 1.7; 7.2). We found no vaccine effects among 5–49 years old. Conclusions: Our study adds to the evidence on direct and indirect protection of a childhood PCV10 vaccine program. Elderlies seem to benefit the most. Findings did not support PCV 10 cross-protection, but indicate replacement at least for ST 8 among the ≥50 years old. Follow-up analyses of IPD surveillance data are needed to fully characterize the magnitude of serotype replacement and further vaccine-attributable IPD reduction with time. [ABSTRACT FROM AUTHOR]

The slipper limpet Crepipatella dilatata, native to Chile and Argentina, was introduced in Spain in 2005. The species was thought to inhabit the region of Rias Bajas, yet recently, putative C. dilatata populations have been documented on the coast of north-central Spain and in the Ebro Delta of the Spanish Mediterranean. Here we undertook a multidisciplinary approach to study the invasion biology of this species. Specifically, two geographically distant populations, one being a successfully established population from O Grove and the other a declining population from Gijon, were studied over the course of four years. Analyses of morphological and developmental traits as well as genetic information confirmed the presence of C. dilatata in these sites. The results revealed polymorphism in anatomical traits and shell shape. Shell shape polymorphism was unevenly distributed among sites and among sexes. Males were monomorphic, while females were polymorphic. Of the female morphotypes encountered, one was absent in the declining population from Gijón. Size at first female maturation and female size were greater in the declining population than in the established population. Reproductive success varied seasonally but not spatially among populations. In the established population, gregariousness was significantly greater; the size when sex changes was found to be plastic and socially controlled. The sex ratio of the declining population was female biased while in the established population the sex ratio changed during the study period from being balanced to being female biased. This change in sex ratio was probably due to higher male mortality. Molecular analyses pointed to the localities of Corral Bay in southern Chile and Puerto Madryn in southern Argentina as potential population sources. The intercontinental import of fresh mussels cultivated in Chilean farms is a likely source of this mussel in Spain. Comparison with available data of native populations of C. dilatata strongly indicate that ecophenotypic plasticity, socially controlled sex change, high gregariousness, increased nurse egg supply to viable larvae during the encapsulated developmental period, later maturation and larger female sizes altogether enhance establishment success of this non-indigenous species. Human-mediated factors like the intraregional mussel trade and transplantation are also likely secondary dispersal mechanisms favouring the spread of this organism. [ABSTRACT FROM AUTHOR]

Background: Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with connective tissue disease. Methods: In this proof-of-concept study, patients with connective tissue disease and mean pulmonary arterial pressure (mPAP) >20 mm Hg were subjected to a supine exercise hemodynamic evaluation before and after administration of intravenous sildenafil 10 mg. Results: Ten patients (four with moderately elevated mPAP 21–24 mm Hg; six with mPAP >25 mm Hg) underwent hemodynamic assessment. All of them showed markedly abnormal exercise hemodynamics. Intravenous sildenafil was well tolerated and had significant hemodynamic effects at rest and during exercise, although without pulmonary selectivity. Sildenafil reduced median total pulmonary resistance during exercise from 6.22 (IQR 4.61–8.54) to 5.24 (3.95–6.96) mm Hg·min·L-1 (p = 0.005) and increased median pulmonary arterial capacitance during exercise from 1.59 (0.93–2.28) to 1.74 (1.12–2.69) mL/mm Hg (p = 0.005). Conclusions: In patients with connective tissue disease who have an abnormal hemodynamic response to exercise, intravenous sildenafil improved adaption of the right ventricular-pulmonary vascular unit to exercise independent of resting mPAP. The impact of acute pharmacological interventions on exercise hemodynamics in patients with pulmonary vascular disease warrants further investigation. Trial registration: Clinicaltrials.gov . [ABSTRACT FROM AUTHOR]

Ricin is a highly-toxic compound derived from castor plant beans. Several incidents involving contamination of residences and buildings due to ricin production or dissemination have occurred in recent years. The goal of this study was to determine whether ricin bioactivity could be attenuated in reasonable time via simple modifications of the indoor environment. Attenuation was assessed on six different materials as a function of temperature, relative humidity (RH), and contact time, using both a pure and crude preparation of the toxin. Ricin bioactivity was quantified via a cytotoxicity assay, and attenuation determined as the difference in ricin recovered from test and positive controls. The results showed that pure ricin could be attenuated successfully, while the crude ricin was generally more persistent and results more variable. We found no significant attenuation in crude ricin after two weeks at typical indoor environmental conditions, except on steel. Attenuation mostly improved with increasing temperature, but the effect of RH varied. For pure ricin, heat treatments at 40°C for 5 days or 50°C for 2–3 days achieved greater than 96% attenuation on steel. In contrast, appreciable recovery of the crude ricin preparation still occurred at 40°C after two weeks. [ABSTRACT FROM AUTHOR]

Background: Pain levels in patients with osteoarthritis (OA) of the knee are commonly assessed by using a numeric scoring system, but results may be influenced by factors other than the patient’s actual physical discomfort or disease severity, including psychosocial and demographic variables. We examined the possible relation between knee-pain scores and several psychosocial, sociodemographic, disease, and treatment variables in 355 patients with knee OA. Methods: The pain-evaluation instrument was a 0- to 10-point rating scale. Data obtained retrospectively from the patients’ medical records were demographic characteristics, body mass index (BMI), concomitant disorders, illicit and prescription drug use, alcohol use, smoking, knee OA treatment, and severity of knee OA indicated by Kellgren-Lawrence (KL) radiographic grade. Univariate and multivariate analyses were performed to determine whether these variables correlated with reported pain scores. Results: On univariate analysis, higher pain scores were significantly associated with Native American or Hispanic ethnicity; a higher BMI; current prescription for an opioid, antidepressant, or gabapentinoid medication; depression; diabetes mellitus; fibromyalgia; illicit drug use; lack of health insurance; smoking; previous knee injection; and recommendation by the clinician that the patient undergo knee surgery. Neither the patient’s sex nor the KL grade showed a correlation. On multivariate analysis, depression, current opioid prescription, and Native American or Hispanic ethnicity retained a significant association with higher pain scores. Conclusions and implications: Our results in a large, ethnically diverse group of patients with knee OA suggest that psychosocial and sociodemographic factors may be important determinants of pain levels reported by patients with knee OA. [ABSTRACT FROM AUTHOR]

We present an effective method to model empirical action potentials of specific patients in the human atria based on the minimal model of Bueno-Orovio, Cherry and Fenton adapted to atrial electrophysiology. In this model, three ionic are currents introduced, where each of it is governed by a characteristic time scale. By applying a nonlinear optimization procedure, a best combination of the respective time scales is determined, which allows one to reproduce specific action potentials with a given amplitude, width and shape. Possible applications for supporting clinical diagnosis are pointed out. [ABSTRACT FROM AUTHOR]

In this paper, we present the design of an electromechanical above-knee active prosthesis with energy storage and regeneration. The system consists of geared knee and ankle motors, parallel springs for each motor, an ultracapacitor, and controllable four-quadrant power converters. The goal is to maximize the performance of the system by finding optimal controls and design parameters. A model of the system dynamics was developed, and used to solve a combined trajectory and design optimization problem. The objectives of the optimization were to minimize tracking error relative to human joint motions, as well as energy use. The optimization problem was solved by the method of direct collocation, based on joint torque and joint angle data from ten subjects walking at three speeds. After optimization of controls and design parameters, the simulated system could operate at zero energy cost while still closely emulating able-bodied gait. This was achieved by controlled energy transfer between knee and ankle, and by controlled storage and release of energy throughout the gait cycle. Optimal gear ratios and spring parameters were similar across subjects and walking speeds. [ABSTRACT FROM AUTHOR]

This manuscript presents an attempt to evaluate the intensity of fire through spatial patterning and thermoluminescence methodology. Previous studies of Layer II-6 Level 2 at the Acheulian site of Gesher Benot Ya‘aqov suggested that hominins differentiated their activities across space, including multiple activities around a hearth reconstructed on the basis of the distribution of burned flint artifacts. A transect of ~4 m was extended from the center of the reconstructed hearth of Level 2 to its periphery in order to examine the intensity of fire. Burned and unburned flint microartifacts were sampled along this transect. The results of earlier and current thermoluminescence (TL) analysis demonstrate a general agreement with the macroscopic determination of burning, indicating that the possibility of misinterpretation based on macroscopic observations is negligible. The TL signal from flint microartifacts close to the hearth’s center shows unambiguous signs of strong heating, whereas with increasing distance from the hearth the TL signal can be interpreted as a result of decreasing temperatures and/or shorter durations of exposure to fire in addition to a decreasing number of flints showing fire damage. Our study shows that TL analysis can identify some variation in fire intensity, which allows a more precise classification of burned flint microartifacts with respect to their heating history. [ABSTRACT FROM AUTHOR]

The homoscleromorph sponge Oscarella carmela, first described from central California, USA is shown to represent two superficially similar but both morphologically and phylogenetically distinct species that are co-distributed. We here describe a new species as Oscarella pearsei, sp. nov. and re-describe Oscarella carmela; the original description was based upon material from both species. Further, we correct the identification of published genomic/transcriptomic resources that were originally attributed to O. carmela, and present new Illumina-sequenced transcriptome assemblies for each of these species, and the mitochondrial genome sequence for O. pearsei sp. nov. Using SSU and LSU ribosomal DNA and the mitochondrial genome, we report the phylogenetic relationships of these species relative to other Oscarella species, and find strong support for the placement of O. pearsei sp. nov. in a distinct clade within genus Oscarella defined by the presence of spherulous cells that contain paracrystalline inclusions; O. carmela lacks this cell type. Oscarella pearsei sp. nov and O. carmela can be tentatively distinguished based upon gross morphological differences such as color, surface texture and extent of mucus production, but can be more reliably identified using mitochondrial and nuclear barcode sequencing, ultrastructural characteristics of cells in the mesohyl, and the morphology of the follicle epithelium which surrounds the developing embryo in reproductively active individuals. [ABSTRACT FROM AUTHOR]

Single parenthood is increasingly common in Western societies but only little is known about its long-term effects. We therefore studied life satisfaction among 641 individuals (ages 18–66 years) who spent their entire childhood with a single mother, 1539 individuals who spent part of their childhood with both parents but then experienced parental separation, and 21,943 individuals who grew up with both parents. Individuals who grew up with a single mother for their entire childhood and to a lesser degree also individuals who experienced parental separation showed a small but persistent decrease in life satisfaction into old age controlling childhood socio-economic status. This decrease was partly mediated by worse adulthood living conditions related to socio-economic and educational success, physical health, social integration, and romantic relationship outcomes. No moderation by age, gender, and societal system where the childhood was spent (i.e. western oriented FRG or socialist GDR) was found. [ABSTRACT FROM AUTHOR]

CO2 seeps in coral reefs were used as natural laboratories to study the impacts of ocean acidification on the pontellid copepod, Labidocera spp. Pontellid abundances were reduced by ∼70% under high-CO2 conditions. Biological parameters and substratum preferences of the copepods were explored to determine the underlying causes of such reduced abundances. Stage- and sex-specific copepod lengths, feeding ability, and egg development were unaffected by ocean acidification, thus changes in these physiological parameters were not the driving factor for reduced abundances under high-CO2 exposure. Labidocera spp. are demersal copepods, hence they live amongst reef substrata during the day and emerge into the water column at night. Deployments of emergence traps showed that their preferred reef substrata at control sites were coral rubble, macro algae, and turf algae. However, under high-CO2 conditions they no longer had an association with any specific substrata. Results from this study indicate that even though the biology of a copepod might be unaffected by high-CO2, Labidocera spp. are highly vulnerable to ocean acidification. [ABSTRACT FROM AUTHOR]

Aquatic exercises are widely used for rehabilitation or preventive therapies in order to enable mobilization and muscle strengthening while minimizing joint loading of the lower limb. The load reducing effect of water due to buoyancy is a main advantage compared to exercises on land. However, also drag forces have to be considered that act opposite to the relative motion of the body segments and require higher muscle activity. Due to these opposing effects on joint loading, the load-reducing effect during aquatic exercises remains unknown. The aim of this study was to quantify the joint loads during various aquatic exercises and to determine the load reducing effect of water. Instrumented knee and hip implants with telemetric data transfer were used to measure the resultant joint contact forces in 12 elderly subjects (6x hip, 6x knee) in vivo. Different dynamic, weight-bearing and non-weight-bearing activities were performed by the subjects on land and in chest-high water. Non-weight-bearing hip and knee flexion/extension was performed at different velocities and with additional Aquafins. Joint forces during aquatic exercises ranged between 32 and 396% body weight (BW). Highest forces occurred during dynamic activities, followed by weight-bearing and slow non-weight-bearing activities. Compared to the same activities on land, joint forces were reduced by 36–55% in water with absolute reductions being greater than 100%BW during weight-bearing and dynamic activities. During non-weight-bearing activities, high movement velocities and additional Aquafins increased the joint forces by up to 59% and resulted in joint forces of up to 301%BW. This study confirms the load reducing effect of water during weight-bearing and dynamic exercises. Nevertheless, high drag forces result in increased joint contact forces and indicate greater muscle activity. By the choice of activity, movement velocity and additional resistive devices joint forces can be modulated individually in the course of rehabilitation or preventive therapies. [ABSTRACT FROM AUTHOR]

From photosynthetic bacteria to mammals, the circadian clock evolved to track diurnal rhythms and enable organisms to anticipate daily recurring changes such as temperature and light. It orchestrates a broad spectrum of physiology such as the sleep/wake and eating/fasting cycles. While we have made tremendous advances in our understanding of the molecular details of the circadian clock mechanism and how it is synchronized with the environment, we still have rudimentary knowledge regarding its connection to help regulate diurnal physiology. One potential reason is the sheer size of the output network. Diurnal/circadian transcriptomic studies are reporting that around 10% of the expressed genome is rhythmically controlled. Zebrafish is an important model system for the study of the core circadian mechanism in vertebrate. As Zebrafish share more than 70% of its genes with human, it could also be an additional model in addition to rodent for exploring the diurnal/circadian output with potential for translational relevance. Here we performed comparative diurnal/circadian transcriptome analysis with established mouse liver and other tissue datasets. First, by combining liver tissue sampling in a 48h time series, transcription profiling using oligonucleotide arrays and bioinformatics analysis, we profiled rhythmic transcripts and identified 2609 rhythmic genes. The comparative analysis revealed interesting features of the output network regarding number of rhythmic genes, proportion of tissue specific genes and the extent of transcription factor family expression. Undoubtedly, the Zebrafish model system will help identify new vertebrate outputs and their regulators and provides leads for further characterization of the diurnal cis-regulatory network. [ABSTRACT FROM AUTHOR]

In mammals, weaning constitutes an important phase in the progression to adulthood. It comprises the termination of suckling and is characterized by several changes in the behaviour of both mother and offspring. Furthermore, numerous studies in rodents have shown that the time point of weaning shapes the behavioural profile of the young. Most of these studies, however, have focused on ‘early weaning’, while relatively little work has been done to study ‘late weaning’ effects. The aim of the present study was therefore to explore behavioural effects of ‘late weaning’, and furthermore to gain insights into modulating effects of weaning age on the consistency of behavioural expressions over time. In total, 25 male and 20 female C57BL/6J mice, weaned after three (W3) or four (W4) weeks of age, were subjected to a series of behavioural paradigms widely used to assess anxiety-like behaviour, exploratory locomotion, and nest building performance. Behavioural testing took place with the mice reaching an age of 20 weeks and was repeated eight weeks later to investigate the stability of behavioural expressions over time. At the group level, W4 mice behaved less anxious and more explorative than W3 animals in the Open Field and Novel Cage, while anxiety-like behaviour on the Elevated Plus Maze was modulated by a weaning-age-by-sex interaction. Furthermore, weaning age shaped the degree of behavioural stability over time in a sex-specific way. While W3 females and W4 males displayed a remarkable degree of behavioural stability over time, no such patterns were observed in W3 males and W4 females. Adding to the existing literature, we could thus confirm that effects of weaning age do indeed exist when prolonging this phase, and were furthermore able to provide first evidence for the impact of weaning age and sex on the consistency of behavioural expressions over time. [ABSTRACT FROM AUTHOR]

Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures—memory selectivity and global memory—to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm—in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials—with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable. [ABSTRACT FROM AUTHOR]

Background: Circulating angiopoietin-1 (Ang-1) has been linked to pulmonary hypertension (PH) in experimental studies. However, the clinical relevance of Ang-1 as a biomarker in PH remains unknown. We aimed to investigate the prognostic and clinical significance of Ang-1 in PH using data from the prospectively recruiting Giessen PH Registry. Methods: Patients with suspected PH (without previous specific pulmonary arterial hypertension [PAH] therapy) who underwent initial right heart catheterization (RHC) in our national referral center between July 2003 and May 2012 and who agreed to optional biomarker analysis were included if they were diagnosed with idiopathic PAH, connective tissue disease-associated PAH (CTD-PAH), PH due to left heart disease (PH-LHD), or chronic thromboembolic PH (CTEPH), or if PH was excluded by RHC (non-PH controls). The association of Ang-1 levels with disease severity (6-minute walk distance and pulmonary hemodynamics) was assessed using linear regression, and the impact of Ang-1 levels on transplant-free survival (primary endpoint) and clinical worsening was assessed using Kaplan—Meier curves, receiver operating characteristic (ROC) analyses, and Cox regression. Results: 151 patients (39, 39, 32, and 41 with idiopathic PAH, CTD-PAH, PH-LHD, and CTEPH, respectively) and 41 non-PH controls were included. Ang-1 levels showed no significant difference between groups (p = 0.8), and no significant associations with disease severity in PH subgroups (p ≥ 0.07). In Kaplan—Meier analyses, Ang-1 levels (stratified by quartile) had no significant impact on transplant-free survival (p ≥ 0.27) or clinical worsening (p ≥ 0.51) in PH subgroups. Regression models found no significant association between Ang-1 levels and outcomes (p ≥ 0.31). ROC analyses found no significant cut-off that would maximize sensitivity and specificity. Conclusions: Despite a strong pathophysiological association in experimental studies, this first comprehensive analysis of Ang-1 in PH subgroups suggests that Ang-1 is not a predictive and clinically relevant biomarker in PH. [ABSTRACT FROM AUTHOR]

Background: Diarrheal disease remains a leading cause of death in children in low-income countries. We investigated the etiology, risk factors and effects on nutritional status of severe diarrhea in children from two districts in Madagascar. Methods: We performed a matched case-control study in 2011 to 2014, on children under the age of five years from Moramanga and Antananarivo. The cases were children hospitalized for severe diarrhea and the controls were children without diarrhea selected at random from the community. Stool samples were collected from both groups. Anthropometric measurements were made during follow-up visits about one and two months after enrolment. Results: We enrolled 199 cases and 199 controls. Rotavirus infection was the most frequently detected cause of diarrhea. It was strongly associated with severe diarrhea (OR: 58.3; 95% CI: 7.7–439.9), accounting for 42.4% (95% CI: 37.6–43.1) of severe diarrhea cases. At the household level, possession of cattle (OR = 0.3; 95% CI: 0.1–0.6) and living in a house with electricity (OR = 0.4; 95% CI: 0.2–0.8) were protective factors. The presence of garbage around the house was a risk factor for severe diarrhea (OR = 3.2; 95% CI: 1.9–5.4). We found no significant association between severe diarrhea and the nutritional status of the children at follow-up visits, but evident wasting at enrolment was associated with a higher risk of severe diarrhea (OR = 9; 95% CI: 4.5–17.9). Conclusions: Severe childhood diarrhea is mostly caused by rotavirus infection. An anti-rotavirus vaccine has already been introduced in Madagascar and should be promoted more widely. However, post-licensing surveillance is required. Interventions to improve the nutritional status of children, preventive measures focused on household and personal hygiene and nutritional rehabilitation during severe diarrheal disease should be reinforced. [ABSTRACT FROM AUTHOR]

Background: Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH. Methods: Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA. Results: 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH. Conclusions: This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA. [ABSTRACT FROM AUTHOR]

Octopuses have large brains and exhibit complex behaviors, but relatively little is known about their cognitive abilities. Here we present data from a five-level learning and problem-solving experiment. Seven octopuses (Octopus vulgaris) were first trained to open an L shaped container to retrieve food (level 0). After learning the initial task all animals followed the same experimental protocol, first they had to retrieve this L shaped container, presented at the same orientation, through a tight fitting hole in a clear Perspex partition (level 1). This required the octopuses to perform both pull and release or push actions. After reaching criterion the animals advanced to the next stage of the test, which would be a different consistent orientation of the object (level 2) at the start of the trial, an opaque barrier (level 3) or a random orientation of the object (level 4). All octopuses were successful in reaching criterion in all levels of the task. At the onset of each new level the performance of the animals dropped, shown as an increase in working times. However, they adapted quickly so that overall working times were not significantly different between levels. Our findings indicate that octopuses show behavioral flexibility by quickly adapting to a change in a task. This can be compared to tests in other species where subjects had to conduct actions comprised of a set of motor actions that cannot be understood by a simple learning rule alone. [ABSTRACT FROM AUTHOR]

Marine chlorophytes of the genus Chlorella are unicellular algae capable of accumulating a high proportion of cellular lipids that can be used for biodiesel production. In this study, we examined the broad physiological capabilities of a subtropical strain (C596) of Chlorella sp. “SAG-211-18” including its heterotrophic growth and tolerance to low salt. We found that the alga replicates more slowly at diluted salt concentrations and can grow on a wide range of carbon substrates in the dark. We then sequenced the RNA of Chlorella strain C596 to elucidate key metabolic genes and investigate the transcriptomic response of the organism when transitioning from a nutrient-replete to a nutrient-deficient condition when neutral lipids accumulate. Specific transcripts encoding for enzymes involved in both starch and lipid biosynthesis, among others, were up-regulated as the cultures transitioned into a lipid-accumulating state whereas photosynthesis-related genes were down-regulated. Transcripts encoding for two of the up-regulated enzymes—a galactoglycerolipid lipase and a diacylglyceride acyltransferase—were also monitored by reverse transcription quantitative polymerase chain reaction assays. The results of these assays confirmed the transcriptome-sequencing data. The present transcriptomic study will assist in the greater understanding, more effective application, and efficient design of Chlorella-based biofuel production systems. [ABSTRACT FROM AUTHOR]

In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections. [ABSTRACT FROM AUTHOR]

Adults prefer to interact with others that are similar to themselves. Even slight facial self-resemblance can elicit trust towards strangers. Here we investigate if preschoolers at the age of 5 years already use facial self-resemblance when they make social judgments about others. We found that, in the absence of any additional knowledge about prospective peers, children preferred those who look subtly like themselves over complete strangers. Thus, subtle morphological similarities trigger social preferences well before adulthood. [ABSTRACT FROM AUTHOR]

Background & Aims: Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. The underlying mechanisms, however, are still not completely understood. Herein, we analysed whether hepatectomy-associated portal hyperperfusion induces a hepatic arterial buffer response, i.e., an adaptive hepatic arterial constriction, which may cause hepatocellular hypoxia and organ dysfunction. Methods: Sprague-Dawley rats underwent 30%, 70% and 90% hepatectomy. Baseline measurements before hepatectomy served as controls. Hepatic arterial and portal venous flows were analysed by ultrasonic flow measurement. Microvascular blood flow and mitochondrial redox state were determined by intravital fluorescence microscopy. Hepatic tissue pO2 was analysed by polarographic techniques. Hepatic function and integrity were studied by bromosulfophthalein bile excretion and liver histology. Results: Portal blood flow was 2- to 4-fold increased after 70% and 90% hepatectomy. This, however, did not provoke a hepatic arterial buffer response. Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy. Microvascular blood flow increased significantly after hepatectomy and functional sinusoidal density was found only slightly reduced. Major hepatectomy further induced a 2- to 3-fold increase of bile flow. This was associated with a 2-fold increase of bromosulfophthalein excretion. Conclusions: Portal hyperperfusion after extended hepatectomy does not induce a hepatic arterial buffer response but reduces mitochondrial redox state and hepatocellular oxygenation. This is not due to a deterioration of microvascular perfusion, but rather due to a relative hypermetabolism of the remnant liver after major resection. [ABSTRACT FROM AUTHOR]

The neonatal management of preterm born infants often results in damage to the developing lung and subsequent morbidity, referred to as bronchopulmonary dysplasia (BPD). Animal models may help in understanding the molecular processes involved in this condition and define therapeutic targets. Our goal was to identify molecular pathways using the earlier described preterm rabbit model of hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31 days) and kept in hyperoxia (95% O2) for 7 days. Controls were preterm pups kept in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity Pathway Analysis (IPA), in order to identify the central molecules responsible for the observed transcriptional changes. We detected 2217 significantly dysregulated transcripts following hyperoxia, of which 90% could be identified. Major pathophysiological dysregulations were found in inflammation, lung development, vascular development and reactive oxygen species (ROS) metabolism. To conclude, amongst the many dysregulated transcripts, major changes were found in the inflammatory, oxidative stress and lung developmental pathways. This information may be used for the generation of new treatment hypotheses for hyperoxia-induced lung injury and BPD. [ABSTRACT FROM AUTHOR]

Diagnosing orthopantomograms (OPTs: panoramic radiographs) is an essential skill dentistry students acquire during university training. While prior research described experts' visual search behavior in radiology as global-to-focal for chest radiographs and mammography, generalizability to a hybrid search task in OPTs (i.e., searching for multiple, diverse anomalies) remains unclear. Addressing this gap, this study investigated visual search of N = 107 dentistry students while they were diagnosing anomalies in OPTs. Following a global-to-focal expert model, we hypothesized that students would use many, short fixations representing global search in earlier stages, and few, long fixations representing focal search in later stages. Furthermore, pupil dilation and mean fixation duration served as cognitive load measures. We hypothesized that later stages would be characterized by elaboration and a reflective search strategy, leading to higher cognitive load being associated with higher diagnostic performance in late compared to earlier stages. In line with the first hypothesis, students' visual search comprised of a three-stage process that grew increasingly focal in terms of the number of fixations and anomalies fixated. Contrary to the second hypothesis, mean fixation duration during anomaly fixations was positively associated with diagnostic performance across all stages. As OPTs greatly varied in how difficult it was to identify the anomalies contained therein, OPTs with above-average difficulty were sampled for exploratory analysis. Pupil dilation predicted diagnostic performance for difficult OPTs, possibly capturing elaborative cognitive processes and cognitive load compared to mean fixation duration. A visual analysis of fine-grained time slices indicated large cognitive load differences towards the end of trials, showcasing a richness-resolution-trade-off in data sampling crucial for future studies using time-slicing of eye tracking data. [ABSTRACT FROM AUTHOR]

Near work is associated with increased activity in the neck and shoulder muscles, but the underlying mechanism is still unknown. This study was designed to determine whether a dynamic change in focus, alternating between a nearby and a more distant visual target, produces a direct parallel change in trapezius muscle activity. Fourteen healthy controls and 12 patients with a history of visual and neck/shoulder symptoms performed a Near-Far visual task under three different viewing conditions; one neutral condition with no trial lenses, one condition with negative trial lenses to create increased accommodation, and one condition with positive trial lenses to create decreased accommodation. Eye lens accommodation and trapezius muscle activity were continuously recorded. The trapezius muscle activity was significantly higher during Near than during Far focusing periods for both groups within the neutral viewing condition, and there was a significant co-variation in time between accommodation and trapezius muscle activity within the neutral and positive viewing conditions for the control group. In conclusion, these results reveal a connection between Near focusing and increased muscle activity during dynamic changes in focus between a nearby and a far target. A direct link, from the accommodation/vergence system to the trapezius muscles cannot be ruled out, but the connection may also be explained by an increased need for eye-neck (head) stabilization when focusing on a nearby target as compared to a more distant target. [ABSTRACT FROM AUTHOR]