Guest Editors’ IntroductionNotebook interfaces – documents combining executable code with output and notes – first became popular as part of computational mathematics software such as Mathematica and Maple. The Jupyter Notebook, which began as part of the IPython project in 2012, is an open source notebook that can be used with a wide range of general-purpose programming languages.Before notebooks, a scientist working with Python code, for instance, might have used a mixture of script files and code typed into an interactive shell. The shell is good for rapid experimentation, but the code and results are typically transient, and a linear record of everything that was tried would be long and not very clear. The notebook interface combines the convenience of the shell with some of the benefits of saving and editing code in a file, while also incorporating results, including rich output such as plots, in a document that can be shared with others.The Jupyter Notebook is used through a web browser. Although it is often run locally, on a desktop or a laptop, this design means that it can also be used remotely, so the computation occurs, and the notebook files are saved, on an institutional server, a high performance computing facility or in the cloud. This simplifies access to data and computational power, while also allowing researchers to work without installing any special software on their own computer: specialized research software environments can be provided on the server, and the researcher can access those with a standard web browser from their computer.These advantages have led to the rapid uptake of Jupyter notebooks in many kinds of research. The articles in this special issue highlight this breadth, with the authors representing various scientific fields. But more importantly, they describe different aspects of using notebooks in practice, in ways that are applicable beyond a single field.We open this special issue with an invited article by Brian Granger and Fernando Perez – two of the co-founders and leaders of Project Jupyter. Starting from the origins of the project, they introduce the main ideas behind Jupyter notebooks, and explore the question of why Jupyter notebooks have been so useful to such a wide range of users. They have three key messages. The first is that Notebooks are centered around the humans using them and building knowledge with them. Next, notebooks provide a write-eval-think loop that lets the user have a conversation with the computer and the system under study, which can be turned into a persistent narrative of computational exploration. The third idea is that Project Jupyter is more than software: it is a community that is nourished deliberately by its members and leaders.The following five articles in this special issue illustrate the key features of Project Jupyter effectively. They show us a small sample of where researchers can go when empowered by the tool, and represent a range of scientific domains.Stephanie Juneau et al. describe how Jupyter has been used to ‘bring the compute to the data’ in astrophysics, allowing geographically distributed teams to work efficiently on large datasets. Their platform is also used for education & training, including giving school students a realistic taste of modern science.Ryan Abernathey et al. , of the Pangeo project, present a similar scenario with a focus on data from the geosciences. They have enabled analysis of big datasets on public cloud platforms, facilitating a more widely accessible ‘pay as you go’ style of analysis without the high fixed costs of buying and setting up powerful computing and storage hardware. Their discussion of best practices includes details of the different data formats required for efficient access to data in cloud object stores rather than local filesystems.Marijan Beg et al. describe features of Jupyter notebooks and Project Jupyter that help scientists make their research reproducible. In particular, the work focuses on the use of computer simulation and mathematical experiments for research. The self-documenting qualities of the notebook—where the response to a code cell can be archived in the notebook—is an important aspect. The paper addresses wider questions, including use of legacy computational tools, exploitation of HPC resources, and creation of executable notebooks to accompany publications.Blaine Mooers describes the use of a snippet library in the context of molecular structure visualization. Using a Python interface, the PyMOL visualization application can be driven through commands to visualize molecular structures such as proteins and nucleic acids. By using those commands from the Jupyter notebook, a reproducible record of analysis and visualizations can be created. The paper focuses on making this process more user-friendly and efficient by developing a snippet library, which provides a wide selection of pre-composed and commonly used PyMOL commands, as a JupyterLab extension. These commands can be selected via hierarchical pull-down menus rather than having to be typed from memory. The article discusses the benefits of this approach more generally.Aaron Watters describes a widget that can display 3D objects using webGL, while the back-end processes the scene using a data visualization pipeline. In this case, the front-end takes advantage of the client GPU for visualization of the widget, while the back-end takes advantage of whatever computing resources are accessible to Python.The articles for this special issue were all invited submissions, in most cases from selected presentations given at JupyterCon in October 2020. Each article was reviewed by three independent reviewers. The guest editors are grateful to Ryan Abernathey, Luca de Alfaro, Hannah Bruce MacDonald, Christopher Cave-Ayland, Mike Croucher, Marco Della Vedova, Michael Donahue, Vidar Fauske, Jeremy Frey, Konrad Hinsen, Alistair Miles, Arik Mitschang, Blaine Mooers, Samual Munday, Chelsea Parlett, Prabhu Ramachandran, John Readey, Petr Škoda and James Tocknell for their work as reviewers, along with other reviewers who preferred not to be named. The article by Brian Granger and Fernando Perez was invited by the editor in chief, and reviewed by the editors of this special issue.Hans Fangohr is currently heading the Computational Science group at the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and is a Professor of Computational Modelling at the University of Southampton, UK. A physicist by training, he received his PhD in Computer Science in 2002. He authored more than 150 scientific articles in computational science and materials modelling, several open source software projects, and a text book on Python for Computational Science and Engineering. Contact him at hans.fangohr@mpsd.mpg.deThomas Kluyver is currently a software engineer at European XFEL. Since gaining a PhD in plant sciences from the University of Sheffield in 2013, he has been involved in various parts of the open source & scientific computing ecosystems, including the Jupyter & IPython projects. Contact him at thomas.kluyver@xfel.euMassimo Di Pierro is a Professor of Computer Science at DePaul University. He has a PhD in Theoretical Physics from the University of Southampton and is an expert in Numerical Algorithms, High Performance Computing, and Machine Learning. Massimo is the lead developer of many open source projects including web2py, py4web, and pydal. He has authored more than 70 articles in Physics, Computer Science, and Finance and has published three books. Contact him at massimo.dipierro@gmail.com

The Small East African (SEA) goat (Capra hircus) breeds are widely distributed in different agro-ecological zones of Tanzania. We report the genetic diversity, maternal origin, and phylogenetic relationship among the 12 Tanzanian indigenous goats populations, namely Fipa (n = 44), Songwe (n = 34), Tanga (n = 33), Pwani (n = 40), Newala (n = 49), Lindi (n = 46), Gogo (n = 73), Pare (n = 67), Maasai (n = 72), Sukuma (n = 67), and Ujiji (n = 67), based on the mitochondrial DNA (mtDNA) D-loop. High haplotype (Hd = 0.9619-0.9945) and nucleotide (π = 0.0120-0.0162) diversities were revealed from a total of 389 haplotypes. The majority of the haplotypes (h = 334) drawn from all the goat populations belonged to Haplogroup A which was consistent with the global scenario on the genetic pattern of maternal origin of all goat breeds in the world. Haplogroup G comprised of 45 haplotypes drawn from all populations except the Ujiji goat population while Haplogroup B with 10 haplotypes was dominated by Ujiji goats (41%). Tanzanian goats shared four haplotypes with the Kenyan goats and two with goats from South Africa, Namibia, and Mozambique. There was no sharing of haplotypes observed between individuals from Tanzanian goat populations with individuals from North or West Africa. The indigenous goats in Tanzania have high genetic diversity defined by 389 haplotypes and multiple maternal origins of haplogroup A, B and G. There is a lot of intermixing and high genetic variation within populations which represent an abundant resource for selective breeding in the different agro-ecological regions of the country.

We describe the role of three-dimensional echocardiography in the assessment of the aortic valve and the aorta. The manuscript is heavily illustrated with figures and movie clips.

Abstract

In this paper, we apply the resolvent operator theory and an approximating technique to derive the existence and controllability results for nonlocal impulsive neutral integro-differential equations with finite delay in a Hilbert space. To establish the results, we take the impulsive functions as a continuous function only, and we assume that the nonlocal initial condition is Lipschitz continuous function in the first case and continuous functions only in the second case. The main tools applied in our analysis are semigroup theory, the resolvent operator theory, an approximating technique, and fixed point theorems. Finally, we illustrate the main results with the help of two examples.

We introduce new reproducing kernel Hilbert spaces on a trapezoidal semi-infinite domain $B_{\infty}$ in the plane. We establish uniform approximation results in terms of the number of nodes on compact subsets of $B_{\infty}$ for solutions to nonhomogeneous hyperbolic partial differential equations in one of these spaces, $\widetilde{W}(B_{\infty})$. Furthermore, we demonstrate the stability of such solutions with respect to the driver. Finally, we give an example to illustrate the efficiency and accuracy of our results.

The interface fracture toughness of SnSb11Cu6/20steel was measured by calculating the critical energy release rate and stress phase angle of the interface crack. A three-point bending test was used to introduce cracks into the bonding interface, and the cohesion model of the bonding interface was established through experimental data. Through finite element analysis of load-deflection curves with and without interface crack propagation, the crack initiation point is found. Then the energy calculation model of crack propagation is established, and the critical energy release rate is obtained using the virtual crack growth criterion. The calculation results of the stress phase angle show that the crack propagation is greatly affected by the normal stress after the babbitt alloy layer fractures. If the strength of the substrate material is weaker, the crack will continue to expand in the tangent perpendicular to the crack tip.

A robust monoclonal antibody (mAb) bioprocess requires physiological parameters such as temperature, pH, or dissolved oxygen (DO) to be well-controlled as even small variations in them could potentially impact the final product quality. For instance, pH substantially affects N-glycosylation, protein aggregation and charge variant profiles, as well as mAb productivity. However, relatively less is known about how pH jointly influences product quality and titer. In this study, we investigated the effect of pH on culture performance, product titer and quality profiles by applying longitudinal multi-omics profiling, including transcriptomics, proteomics, metabolomics and glycomics, at three different culture pH set points. The subsequent systematic analysis of multi-omics data showed that pH set points differentially regulated various intracellular pathways including intracellular vesicular trafficking, cell cycle, and apoptosis, thereby resulting in differences in specific productivity, product titer and quality profiles. In addition, a time-dependent variation in mAb N-glycosylation profiles, independent of pH was identified to be mainly due to the accumulation of mAb proteins in the endoplasmic reticulum (ER) over culture time, disrupting cellular homeostasis. Overall, this multi-omics-based study provides an in-depth understanding of the intracellular processes in mAb-producing CHO cell line under varied pH conditions and could serve as a baseline for enabling the quality optimization and control of mAb production.

Aim: Artemisia annua L. is the one and only original plant used to isolate artemisinin which is a highly effective remedy to fight malaria. Climate change leads to change of distribution and suitable range for many species and A. annua is no exception. However, it is not clear that the potential distribution and suitable range change of this unique plant under climate change. Therefore, we present this research to study its change in the future. Location: Global. Methods: Since the accuracy of species distribution models was affected by occurrence records and environmental variables, 1062 presence records and 7 variables were picked out to build ensemble models with 10 different algorithms by means of biomod2 under current and future climate scenarios. Results: At present, except SRE, the AUC values of the rest models were greater than 0.8, and the TSS values were greater than 0.6, the values of ensemble model were 0.968 and 0.826 respectively. Mean temperature of driest quarter was the dominant factor to shape the range of A. annua and its optimum interval ranged from 4.8 to 23.3ºC. The high suitable habitats of A. annua were mainly located in Eastern Asia, Western Europe, Central Europe. In the future, the high suitable area would decline at 15.55% to 25.87%. Main conclusions: Ensemble models showed it performed better than any the single one. At present, the high suitable habitat simulated by ensemble model was in accordance with the actual occurrence records. In the future, the high suitable habitat for A. annua would move northeast, and disappear in North America. They would increase with time under each SSP, but sharply decline while comparing with the current one. This study can be used to protect wild resource and guide cultivation for A. annua, which would make modest contribution to fight malaria.

A document by Alexandra Emms. Click on the document to view its contents.

Seasonal influenza infection waves occur both in northern and southern hemispheres every year. Despite the differences in influenza virus surface antigens and virulence of seasonal subtypes, manufacturers are well-adapted to respond to this periodical vaccine demand. Due to decades of influenza virus research, the development of new influenza vaccines is relatively straight-forward. Nevertheless, compared to the recent Covid-19 pandemic where a vaccine is not yet available, influenza vaccine manufacturing would be a major bottleneck for the rapid supply of billions of doses required worldwide. In particular, egg-based vaccine production would be difficult to schedule and shortages of other egg-based vaccines with high demands also have to be anticipated. Cell culture-based production systems enable manufacturing of large amounts of vaccines within a short time frame and expand significantly our options to respond to pandemics and emerging viral diseases. In this work, we present an integrated process for the production of inactivated influenza A virus vaccines based on a MDCK suspension cell line cultivated in a chemically defined medium. Very high titers of 3.6 log10(HAU/100 µL) were achieved using fast growing MDCK cells at concentrations up to 9.5 × 106 cells/mL infected with influenza A/PR/8/34 H1N1 virus in 1 L stirred tank bioreactors. A combination of two membrane-based chromatography steps enabled full recovery for the virus capture and up to 80 % recovery for the virus polishing step, respectively. Purified virus particles showed a homogenous size distribution around a mean diameter of 80 nm. Based on a monovalent dose of 15 µg hemagglutinin (SRID assay), the level of total protein was 58 µg and the level of host cell DNA contamination was below 10 ng. Furthermore, all process steps can be fully scaled up to industrial quantities for commercial manufacturing of either seasonal or pandemic influenza virus vaccines. Fast production of up to 300 vaccine doses per liter within 4 to 5 days makes this process competitive not only to other cell-based processes, but to egg-based processes as well.

This paper starts with an overview of the application of the three guidelines (GL) of the German Research Association of Mechanical Engineers (FKM). Each of these provides algorithms for calculating fatigue lives of components under constant or variable amplitude loading, however, with underlying different failure criteria, i.e. technical crack initiation life (GL-nonlinear), fatigue crack growth life (GL-fracture mechanics), and total fracture life (GL-linear). This paper introduces the U-Concept which has been evaluated from a large structural durability database. The U-Concept is a small add-on to the Local Strain Approach (LSA) which is the backbone of the GL-nonlinear. It enables 1) to directly calculate the fatigue life to total fracture based on elastic-plastic material behaviour according to the LSA, or 2) to estimate the remaining fatigue life from crack initiation to fracture without a crack growth simulation.

Letter to the Editor, BJOG Title: ESMiE confidential enquiry: Broader view besides focus on errors by birth-attendants.Re: Rowe R, Draper ES, Kenyon S, Bevan C, Dickens J, Forrester M, Scanlan R, Tuffnell D, Kurinczuk JJ. Intrapartum-related perinatal deaths in births planned in midwifery-led settings in Great Britain: findings and recommendations from the ESMiE confidential enquiry. BJOG 2020;127:1665–1675.Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKShort running title: ESMiE enquiry: broader viewEmail: s.sholapurkar@nhs.net Tel: 07906620662Word count: 500Corresponding Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKStatement of interest: The author has no conflict of interest or funding to declare.

Following acute traumatic brain injury, cerebral salt wasting (CSW) syndrome is considered as an important cause of hyponatremia apart from syndrome of inappropriate antidiuretic hormone. Differentiation between the two syndromes is crucial for the initiation of an adequate treatment. So we report a pediatric case.

Groundwater pollution of the watershed is mainly influenced by the multifaceted interactions of geogenic and anthropogenic processes. In this study, classic chemical and multivariate statistical methods were used to assess the groundwater quality and identify the potential pollution sources affecting the groundwater quality of Galma sub-watershed in a tropical savannah. For this purpose, the dataset of 18 groundwater quality variables covering 57 different sampling boreholes (BH) was used. The order of abundance of the main cations and anions in the samples are Ca2+ > Na+ > Mg2+ > K+ and HCO3− > Cl− > SO4−2 > NO3− respectively. Piper diagram classified the groundwater types of the watershed into mixed Ca–Mg–Cl type of water, which means no cations and anions exceeds 50%. The second dominant water type was Ca–Cl. The Mg–HCO3 water type was found in BH 9, and Na–Cl water type in BH 29 respectively. Hierarchical cluster analysis grouped the sampling boreholes into five statistically significant clusters based on similarities of groundwater quality characteristics. Principal component extracted two principal components that explained around 65% of the total variance, which natural and anthropogenic processes especially agricultural activities as the dominant factors affecting the groundwater quality. The findings of this study are useful to the policy and decision-makers for formulating efficient groundwater utilization and management plans for the groundwater resources.

Re: Training in the use of intrapartum electronic fetal monitoring with cardiotocography: systematic review and meta‐analysis. Cardiotocography training is a complex intervention and requires complex evaluations: a letter to editor.Lightly K, Weeks AD, Scott HCorrespondence to Dr Kate Lightly – klightly@liverpool.ac.uk07875642837Clinical Research Fellow, Sanyu Research Unit, University of Liverpool and Liverpool Women’s NHS Foundation Trust, members of Liverpool Health Partners, Crown Street, Liverpool, L8 7SS.Professor Andrew D WeeksProfessor of International Maternal Health, Sanyu Research Unit, University of Liverpool and Liverpool Women’s NHS Foundation Trust, members of Liverpool Health Partners, Crown Street, Liverpool, L8 7SS.Professor Hazel ScottDean of School of Medicine, School of Medicine, University of Liverpool, Cedar House, Liverpool, L69 3GE.Running title - CTG training requires complex evaluationsWe congratulate Kelly et al on their review on the effects of training in cardiotocography (CTG).i It is a critical step towards understanding how to correctly implement CTG training. However, we query the relevance of some of the included studies and whether using Kirkpatrick’s model adequately captures all of the relevant complexities. We believe that further work is needed to understand how such training will impact on practice.Some of the CTG research projects reviewed were poorly representative of the needs of clinicians tasked with improving fetal monitoring in their hospitals. For clinicians, their population of interest is practising clinicians who work on labour wards (sometimes infrequently); studies involving undergraduates alone may not be generalisable. Training in intermittent auscultation is also relevant. Considerable detail on the training intervention is required, including not only the format of teaching, but the duration, curriculum and proportion of relevant staff trained. Detail is also required of supporting interventions and context, as training alone is unlikely to impact change. Many would consider ‘no training’ unethical and therefore not a relevant comparator . In the UK, CTG training and competency is now required for all maternity staff.ii The ultimate aim of CTG (and therefore CTG training) is to detect the hypoxic fetus, so that timely intervention can be undertaken to avoid perinatal harm, without unnecessary intervention. Therefore, the outcomes of interest have to include intrapartum stillbirths, hypoxic ischaemic encephalopathy and mode of delivery.Kirkpatrick’s model was used in this review to evaluate training at four levels (reaction, knowledge, behaviour change and organisational performance). However, it does not attempt to understand why interventions work, or the context, or the causal pathways between training and change in practice.iii Whether participants like training (‘reaction’) is of little relevance, and knowledge acquisition (‘knowledge’) is a proxy which does not equate with improved on the job performance and outcomes. Maternal and perinatal outcomes (‘performance’) were only collected in a small number of studies.CTG training is a complex intervention which aims to create change, not simply knowledge acquisition. We therefore believe that a formal Realist Evaluation is needed. This emerging methodology has been used successfully to understand healthcare change processes and supplement traditional Cochrane style reviews. It aims to understand why complex interventions work, how, for whom, in what context and to what extentiv. Collaboration with the relevant authors to gain detailed intervention descriptions, with a realist approach, may add some much needed explanatory power to this critical subject.Training alone is unlikely to impact change. Even the best educational package will fail without the necessary support - it needs an educational and working culture which supports learning and change, aligned and clear policies, and motivated, well supported drivers and leaders.How doctors learn and what supports them to put new knowledge into practice are key research questions. High quality, methodologically appropriate, properly funded studies are needed to address these questions. Not answering them means many research findings are redundant, as they simply will not be implemented.ReferencesI Kelly S, Redmond P, King S, Oliver‐Williams C, Lamé G, Liberati E et al. Training in the use of intrapartum electronic fetal monitoring with cardiotocography: systematic review and meta‐analysis. BJOG. 2021; 00: 1–12. https://doi.org/10.1111/1471-0528.16619ii NHS England. Saving Babies’ Lives Version Two. A care bundle for reducing perinatal mortality. London: NHS England 2019. [cited 2021 Feb 3]. Available from: www.england.nhs.ukiii Moreau KA. Has the new Kirkpatrick generation built a better hammer for our evaluation toolbox? Med Teach. 2017 Sep; 39(9): 999-1001. https://doi.org/10.1080/0142159X.2017.1337874iv Wong G, Westhorp G, Greenhalgh J, Manzano A, Jagosh J, Greenhalgh T. Quality and reporting standards, resources, training materials and information for realist evaluation: the RAMESES II project. Health Services and Delivery Research. 2017 5 (28): 1–108. https://doi.org/10.3310/hsdr05280.Acknowledgements – NilDisclosure of interests - NilContribution to authorshipKL wrote the first draft of this letter and then it was revised by AW and HS.Details of ethics approval – N/AFunding – Dr Lightly’s PhD entitled “Improving intrapartum fetal monitoring in India: A mixed methods approach” is funded by MRC/DfID/Wellcome Trust Joint Global Health Trials Fund. MR/R006/1801

We consider a new generic reaction-diffusion system, given as the following form: ∂u/∂t - div(g(│(∇u_σ)│)∇u)=f(t,x,u,v,∇v), in Q_T ∂v/∂t - d_v Δv=p(t,x,u,v,∇u), in Q_T u(0,.)=u_0, v(0,.)=v_0, in Ω (1) ∂u/∂η=0, ∂v/∂η=0, in ∑_T. Where Ω=]0,1[?×]0,1[, Q_T =]0,T [? and T =]0,T [?, (T > 0), η is an outward normal to domain Ω and u_0, v_0 is the image to be processed, x ∈Ω, σ >0, ∇u_σ= u∗ ∇G_σ and G_σ= 1/√2πσ exp(-│x│^2/4σ). In this study we are going to proof that there is a global weak solution to the ptoblem (1), we truncate the system and show that it can be solved by using Schauder fixed point theorem in Banach spaces. Finally by making some estimations, we prove that the solution of the truncated system converge to the solution of the problem.

Several recent publications have stated that epistatic fitness interactions cause the fixation of inversions that suppress recombination among the loci involved. Under this model, however, the suppression of recombination in an inversion heterozygote creates a form of heterozygote advantage, which prevents the inversion from becoming fixed by selection. This process has been explicitly modelled by previous workers.

Corticosteroid administration can be a trigger of the onset of invasive pulmonary aspergillosis in patients with hepatocellular carcinoma. It is necessary to pay attention to the presence of cirrhosis, which may be the basis of hepatocellular carcinoma especially when administering systemic corticosteroid.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition which most often accompanies a malignant disease and involves a hypercoagulable state. We report the incidental finding of a scarce case of NBTE affecting the tricuspid valve in a patient with metastatic pancreatic carcinoma complicated by severe venous and arterial thromboembolisms.

Stress visualization within 3-dimensional particles undergoing dynamic processes can greatly advance our understanding of complex particle behaviors. Traditional photoelastic stress visualization methods suffer inherent limitations from lack of available technology for complex particle production. Recently, 3D-printing has created new possibilities for enhancing the scope of stress analysis within physically representative granules. Here, we investigate opportunities offered by 3D-printing a granular material with photoelastic properties. We report the results of X-ray computed tomography and 3D-printing, combined with traditional photoelastic analysis, to visualize strain exhibited within simple discs to reproduced coffee beans. We find that the choice of print layer orientation with respect to the force load affects the optical properties of the discs, without a significant difference in their mechanical properties. Furthermore, we present a first, semi-quantified, measurement of stresses within 3D-printed particles of complex shape. The promising data shows potential for applying this method to complex assemblies of 3-dimensional particles.

Aim: To analyze the appropriateness of DOAC dosing and determinants for under-and overdosing as well as acceptance and implementation rates of interventions by clinical pharmacists. Methods: Cross-sectional study from January 2019-December 2019 in a tertiary hospital in hospitalized patients with atrial fibrillation on DOACs (n=1688). Primary outcome was the proportion of patients with inappropriate DOAC prescribing with identification of determinants for under-and overdosing. Secondary outcomes included acceptance and implementation rates of pharmacists’ advices and determination of reasons for non-acceptance/non-implementation. Results: In 16.9% of patients, inappropriate prescribing was observed. For all DOACs considered together, body weight<60 kg(OR 0.46 [0.27-0.77]), edoxaban use(OR 0.42 [0.24-0.74]), undergoing surgery(OR 0.57 [0.37-0.87]) and being DOAC naïve(OR 0.45 [0.29-0.71]) were associated with a significantly lower odds of underdosing. Bleeding history(OR 1.86 [1.24-2.80]) and narcotic use(OR 1.67 [1.13-2.46]) were associated with a significantly higher odds for underdosing. Determinants with a significantly higher odds of overdosing were renal impairment(OR 11.29 [6.23-20.45]) and body weight<60 kg(OR 2.34 [1.42-3.85]), whereas the use of dabigatran(OR 0.24 [0.08-0.71]) and apixaban(OR 0.18 [0.10-0.32]) were associated with a significantly lower odds of overdosing compared to rivaroxaban. Physicians accepted the pharmacists’ advice in 179 cases (79.2%) consisting of 92 (51.4%) advices for underdosing, 82 (45.8%) for overdosing and 5 (2.8%) for contraindications. The advices were effectively implemented for 75 (81.5%) underdosed, 69 (84.1%) overdosed and 4 (80.0%) contraindicated cases. Conclusion: Inappropriate DOAC prescribing remains common. Clinical services led by pharmacists helps physicians to reduce the number of inadequate prescriptions for high risk medications such as DOACs.

Purpose: The high percentage of asymptomatic patients and the non-high sensitivity of real-time reverse transcription-polymerase chain reaction (RT-PCR) test on nasopharyngeal swab cause some healthcare workers to be infected but asymptomatic and a source of spread of the epidemic. This study aimed to verify if the lung ultrasound (LUS) had enough high negative predictive value to rule out coronavirus disease 2019 (COVID-19) among a population of healthcare workers operating in the Emergency Department. Methods: A multicenter prospective observational study was conducted, enrolling healthcare workers among the staff of two Emergency Departments in Northeast Italy. The definitive diagnosis of COVID-19 was established by an adjudication committee, based on the clinical data and RT-PCR on nasopharyngeal swab result. Results: From March 30, 2020, to April 22, 2020, we enrolled 155 cases. The adjudication committee determined two true positives for COVID-19. Twenty-one healthcare workers presented suggestive symptoms (2 true positives and 19 false positives). The nasopharyngeal swab was positive in one case (1 false-negative case). LUS was suggestive for COVID-19 pneumonia in 4 cases (2 false-positive cases). The diagnostic accuracy of LUS was 98.7% (95% CI 95.4%-99.8%). The sensitivity and the specificity of LUS were 100% (95% CI 15.8% -100%) and 98.7% (95% CI 95.4% - 99.8%), respectively. The negative predictive value was 100% (95% CI 100% -100%). Conclusion: LUS has a good enough negative predictive value for ruling out COVID-19 in a population of healthcare workers exposed to COVID-19.

Using ecological, taxonomic and phylogenetic approaches, we here describe geographically isolated symbiotic relationships between a gobiid fish and two misdescribed alpheid snapping shrimps. This was discovered in the southwestern province of the Persian Gulf, more specifically, in the harsh hyperarid intertidal zone separating the coastal ecosystem from the Middle East desert. Phylogenetic results based on the 16S rRNA gene indicate the existence of two new cryptic species within the Alpheus lobidens De Haan, 1849 species complex, described and named here as Alpheus qatari n. sp. and Alpheus arabicus n. sp. Furthermore, phylogeographic results suggest resurrection of Alpheus crassimanus Heller, 1865 within the same species complex. A phylogenetic comparison of the endemic Arabic goby Cryptocentroides arabicus (Gmelin, 1789) with some of its congeners confirms its presence along both sides of the Persian Gulf. Ecologically noteworthy is the facultative symbiotic interaction between this endemic Arabic goby with the two mentioned endemic alpheid shrimps within two distinct ecosystems. Therefore, we herewith report a case of exceptional symbiosis of a littoral fish species with two potential partners, niche-restricted to shallow intertidal zones, however, with niche differentiation defined by the adaptability of each associated shrimp species. Furthermore, the presence of the goby depends on suitable sediment needed for burrowing: either gravel in the periphery of coral reefs, or mud in the periphery of mangrove ecosystems. The corresponding ecology, taxonomic status and phylogeography are discussed with respect to the recorded facultative character of the symbiotic relationship.