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The main objective of this paper is to introduce an Allen-type index of differentiation based on cost functions. With this index, we create an economic measure of product differentiation that quantifies differences between products. Applied research has some generally accepted economic measures, for example, the Herfindahl-Hirschman Index for market concentration, or the Gini coefficient for inequality. Product differentiation, however, does not yet have an established measure. Our objective is to fill that gap and introduce a measure that can be used in market-related applied research such as market power, antitrust, price indexes, or market strategy. To operationalize the index, we introduce the concept of a core product and use cost functions to measure the degree of differentiation from the core product. To demonstrate the use of the index, we study the effect of product differentiation on price formation in the airline industry using an enhanced hedonic model. The model is empirically tested on 103,980 observations of quarterly US domestic airfare data between 2002 and 2016 and shows that product differentiation has a significant effect on both price and mark-up

Bleeding and thrombosis are major clinical problems with high morbidity and mortality. Treatment modalities for these diseases have improved in recent years, but there are many clinical questions remaining and a need to advance diagnosis, management, and therapeutic options. Basic research plays a fundamental role in understanding normal and disease processes, yet this sector has observed a steady decline in funding prospects thereby hindering support for studies of mechanisms of disease and therapeutic development opportunities. With the financial constraints faced by basic scientists, the ISTH organized a basic science task force (BSTF), comprising Scientific and Standardization Committee subcommittee chairs and co-chairs, to identify research opportunities for basic science in hemostasis and thrombosis. The goal of the BSTF was to develop a set of recommended priorities to build support in the thrombosis and hemostasis community and to inform ISTH basic science programs and policy making. The BSTF identified three principal opportunity areas that were of significant overarching relevance: mechanisms causing bleeding, innate immunity and thrombosis, and venous thrombosis. Within these, five fundamental research areas were highlighted: blood rheology, platelet biogenesis, cellular contributions to thrombosis and hemostasis, structure-function protein analyses, and visualization of hemostasis. This position paper discusses the importance and relevance of these opportunities and research areas, and the rationale for their inclusion. These findings have implications for the future of fundamental research in thrombosis and hemostasis to make transformative scientific discoveries and tackle key clinical questions. This will permit better understanding, prevention, diagnosis, and treatment of hemostatic and thrombotic conditions. ispartof: JOURNAL OF THROMBOSIS AND HAEMOSTASIS vol:20 issue:6 pages:1496-1506 ispartof: location:England status: published

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.

Este artículo está sujeto a una licencia CC BY-NC 4.0, This article analyses the review, acceptance and publication dates of a sample of 21,890 articles from 326 Ibero-American scientific journals from all subject areas and countries included in the Latindex Catalogue 2.0 and published between 2018 and 2020 (freely available as an open access dataset). The aim is to discover evaluation and publication times. The evaluation process takes a median of 110 days, the publication process, a median of 82 days, and the whole process, a median of 224 days. Statistical differences are found according to periodicity, subject areas, countries, existence of a printed version and article type (Call for Papers or General articles). From the data we find that the delay in publication is longer than publishers themselves report to the DOAJ. STEM areas present the most similarity in publication patterns, having a higher number of evaluation days (Ed) than publication days (Pd); Arts and Humanities present the opposite pattern, with a higher Pd than Ed. In the case of Social Sciences, the times are similar. General articles and Call for Papers articles differ in terms of Ed, but not Pd, indicating that Call for Papers revisions are faster.

Recommendations represent the core messages of guidelines, and are particularly important when the body of scientific evidence is rapidly growing, as in the case of heart failure (HF). The main messages from two latest major HF guidelines, endorsed by the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA), are partially overlapping, starting from the four pillars of treatment for HF with reduced ejection fraction. Some notable differences exist, in part related to the timing of recent publications (most notably, the Universal Definition of HF paper and the EMPEROR-Preserved trial), and in part reflecting differing views of the natural history of HF (with a clear differentiation between stages A and B HF in the ACC/AHA/HFSA guidelines). Different approaches are proposed to specific issues such as risk stratification and implantable cardioverter defibrillator use for primary prevention in HFrEF patients with non-ischaemic aetiology. The ACC/AHA/HFSA guidelines put a greater emphasis on some issues that are particularly relevant to the US setting, such as the cost-effectiveness of therapies and the impact of health disparities on HF care. A comparison between guideline recommendations may give readers a deeper understanding of the ESC and ACC/AHA/HFSA guidelines, and help them apply sensible approaches to their own practice, wherever that may be in the world. A comparison may possibly also help further harmonization of recommendations between future guidelines, by identifying why some areas have led to conflicting recommendation, even when ostensibly reviewing the same published evidence.

It remains unclear how effective COVID-19 vaccinations will be in patients with weakened immunity due to diseases, transplantation, and dialysis. We conducted a systematic review comparing the efficacy of COVID-19 vaccination in patients with solid tumor, hematologic malignancy, autoimmune disease, inflammatory bowel disease, and patients who received transplantation or dialysis. A literature search was conducted twice using the Medline/PubMed database. As a result, 21 papers were included in the review, and seropositivity rate was summarized by specific type of disease, transplantation, and dialysis. When different papers studied the same type of patient group, a study with a higher number of participants was selected. Most of the solid tumor patients showed a seropositivity rate of more than 80% after the second inoculation, but a low seropositivity was found in certain tumors such as breast cancer. Research in patients with certain types of hematological malignancy and autoimmune diseases has also reported low seropositivity, and this may have been affected by the immunosuppressive treatment these patients receive. Research in patients receiving dialysis or transplantation has reported lower seropositivity rates than the general population, while all patients with inflammatory bowel disease have converted to be seropositive. Meta-analysis validating these results will be needed, and studies will also be needed on methods to protect patients with reduced immunity from COVID-19. This article is protected by copyright. All rights reserved.

Aim To study neurotransmitter status in children with early epileptic and developmental and epileptic encephalopathy (DEE) and to explore the clinical response to dopaminergic and serotoninergic therapies in a group of patients. Method Two hundred and five patients (111 males [54.1.%] and 94 females [45.9%], mean age 10 months at the onset of epilepsy [SD 1 year 1 month], range 0-3 year) with epileptic encephalopathy/DEE were recruited, including those with West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, myoclonic encephalopathy in non-progressive disorders, infantile spasms, Doose syndrome, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and those unclassified. Cerebrospinal fluid (CSF) neurotransmitter studies and patients' medical records were reviewed. Additionally, we present clinical data of 10 patients with low CSF neurotransmitter levels who received dopaminergic/serotoninergic treatments. Results Abnormal neurotransmitter values were identified in 68 (33%) patients. 5-Hydroxyindoleacetic acid (5-HIAA) deficit was the most prevalent alteration (91%). Low CSF 5-HIAA levels were significantly higher in 1- to 3-year-old children. A negative significant correlation was found between 5-HIAA levels and epilepsy duration before CSF study (Spearman's rho=-0.191, p=0.007). Abnormalities in deep grey matter were associated with low levels of CSF homovanillic acid and 5-HIAA. Ten patients with low CSF neurotransmitter levels received dopamine and/or serotonin therapies. Six of them showed initial decrease of seizure frequency and severity and maintained improvement in some neurodevelopmental skills. Interpretation A considerable number of patients showed neurotransmitter abnormalities. Age at seizure onset and duration of epilepsy before CSF study were the principal factors related to neurotransmitter depletion. Early monoamine supplementation would seem advisable as a neuroprotective strategy. What this paper adds 5-Hydroxyindoleacetic acid homeostasis is especially vulnerable in patients with epileptic encephalopathy/developmental and epileptic encephalopathy. Age of seizure onset and duration of epilepsy are determinants of neurotransmitter depletion.

This paper examines the detailed performance of an Integrated-Damping-System (IDS) approach which was recently introduced to provide large damping levels by enabling two parts of a building to move independently through a parallel arrangement of springs and fluid viscous dampers. Extensive assessments into the characteristics and distribution of constituent dampers are illustrated through the dynamic response of a typical 300m central-core building. Besides examining the system performance under typical wind conditions and selected seismic excitations, five damper placement methods are assessed for various linear and nonlinear damper exponents. It is shown that intermediate exponents provide the best overall response. However, when the design targets a particular damping, deformation or acceleration related performance parameter, specific combinations of damper exponent and distribution can result in an optimal application. Most importantly, due to the underlying IDS nature, which acts as an inherent large-mass damper, the findings show that the overall performance is not highly sensitive to the damper placement and does not necessitate the use of an advanced distribution. Whilst specific placements can be adopted to refine targeted performance aspects where necessary, simple and practical uniform or stiffness proportional arrangements can be consistently employed with the IDS to provide a highly effective solution.

This paper examines the varying ways religious devotees utilize, negotiate, embrace and reject religious authorities in their everyday lives. Ethnographically exploring the ways that Orthodox Jews share reproductive-decisions with rabbinic authorities, I demonstrate how some sanctify rabbinic rulings, while others dismiss them, or continue to “shop around” until they find a rabbinic opinion that resonates with their personal desires. These negotiations of religious authority and ethical freedom are worked out across a biographical trajectory, opening new possibilities to explore how religious authority fluctuates and changes over the life-course. I argue that analysis of engagement with rabbis without attention to the inner-diversity of interpretations and practices perpetuates a hegemonic and over-harmonious picture of religious authority. Highlighting these variations, I show how the process of consultation was more significant than mere submission to religious rulings. Religious consultation, in itself, then constitutes a significant node for making an ethical Jewish life. Attending to these aspects of religious authority has great potential to further develop and contextualize the field of ethical freedom while complicating binary models of submission versus resistance. My approach demonstrates the need to broaden our anthropological tools to better understand the ways individuals share everyday decisions with mediators of authoritative knowledge.

Vascular malformations (VMs) of the central nervous system (CNS) include a wide range of pathological conditions related to intra and extracranial vessel abnormalities. Although some VMs show typical neuroimaging features, other VMs share and overlap pathological and neuroimaging features that hinder an accurate differentiation between them. Hence, it is not uncommon to misclassify different types of VMs under the general heading of arteriovenous malformations. Thorough knowledge of the imaging findings of each type of VM is mandatory to avoid these inaccuracies. Conventional MRI sequences, including MR angiography, have allowed the evaluation of CNS VMs without using ionizing radiation. Newer MRI techniques, such as susceptibility-weighted imaging, black blood sequences, arterial spin labeling, and 4D flow imaging, have an added value of providing physiopathological data in real time regarding the hemodynamics of VMs. Beyond MR images, new insights using 3D printed models are being incorporated as part of the armamentarium for a noninvasive evaluation of VMs. In this paper, we briefly review the pathophysiology of CNS VMs, focusing on the MRI findings that may be helpful to differentiate them. We discuss the role of each conventional and advanced MRI sequence for VMs assessment and provide some insights about the value of structured reports of 3D printing to evaluate VMs.

In 2014, drug-induced enterocolitis syndrome (DIES) was described for the first time. It is still a poorly known disease with symptoms that typically resemble those of food protein-induced enterocolitis syndrome (FPIES). To date, six more cases of DIES have been described and new clinical diagnostic criteria have been proposed based on those in the international guidelines for FPIES. In this paper, the authors describe three more cases of DIES. In addition, similarities and differences with FPIES have been deeply analyzed. To date, several unanswered questions need to be addressed, but clinicians must be instructed how to identify DIES, in order to make an allergy workup and give definite therapeutic indications to patients, especially in children where DIES seems to be more frequent.

The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose. This position paper of the European Academy of Allergy and Clinical Immunology (EAACI) agrees with these recommendations and clarifies that there is no contraindication to administer these vaccines to allergic patients who do not have a history of an allergic reaction to any of the vaccine components. Importantly, as is the case for any medication, anaphylaxis may occur after vaccination in the absence of a history of allergic disease. Therefore, we provide a simplified algorithm of prevention, diagnosis and treatment of severe allergic reactions and a list of recommended medications and equipment for vaccine centres. We also describe potentially allergenic/immunogenic components of the approved vaccines and propose a workup to identify the responsible allergen. Close collaboration between academia, regulatory agencies and vaccine producers will facilitate approaches for patients at risks, such as incremental dosing of the second injection or desensitization. Finally, we identify unmet research needs and propose a concerted international roadmap towards precision diagnosis and management to minimize the risk of allergic reactions to COVID-19 vaccines and to facilitate their broader and safer use.

The selective recognition of tyrosine residues in peptides is an appealing approach to inhibiting their tyrosine kinase (TK)‐mediated phosphorylation. Herein, we describe pseudopeptidic cages that efficiently protect substrates from the action of the Src TK enzyme, precluding the corresponding Tyr phosphorylation. Fluorescence emission titrations show that the most efficient cage inhibitors strongly bind the peptide substrates with a very good correlation between the binding constant and the inhibitory potency. Structural insights and additional control experiments further support the proposed mechanism of selective supramolecular protection of the substrates. Moreover, the approach also works in a completely different kinase‐substrate system. These results illustrate the potential of supramolecular complexes for the efficient and selective modulation of TK signaling., How to spare Tyr: The selective recognition of tyrosine residues by pseudopeptidic cages protects the substrates from Src kinase‐promoted phosphorylation. The Tyr kinase‐inhibiting activity of the cages can be satisfactorily explained by the formation of host‐guest complexes. This supramolecular approach represents an appealing alternative to modulating Tyr kinase activity by substrate recognition.

BACKGROUND Biogas is a valuable carbon-free renewable energy source that can be produced from anaerobic digestion of organic waste. Accordingly, biogas production is promoted worldwide in efforts to reduce carbon emissions and optimize the recovery of resources from waste streams. In this paper the biogas production from bioresidues collected in the capital area of Reykjavik was modelled in Aspen Plus v10. RESULTS Municipal solid waste (MSW), food waste (FW) and lignocellulosic biomass (LCB) were the feedstocks used in this research. A total of 16 scenarios were simulated at thermophilic temperature conditions of 55°C. Each scenario accounted for different inlet mass flows, varying the kind of feedstock, i.e. MSW, FW, LCB, or co-digestion of various feedstocks, using two model approaches: (i) one digestion stage and (ii) two stages coupled in series. Sizing, costing and environmental aspects were analysed for all the scenarios. A sensitivity analysis was carried out by changing the substrate concentration and studying its effect on the methane mass flow. Simulations showed biogas yields measured in millilitres per gram of volatile solids (VS) in the range 305.5-406.4 mL g-1 VS (single-stage approach); and biogas yields ranging from 64.78 to 358.8 mL g-1 VS (two-stage approach). Maximum methane yields were obtained using LCB as feedstock resulting in 106.0 mL g-1 VS. CONCLUSIONS From a technical viewpoint the highest biogas yield is obtained when using MSW whereas optimum calorific value of biogas and electrical power potential is achieved working in co-digestion of various feedstocks. This work was supported by the COST Action CA17133 ‘Imple-menting nature-based solutions for creating a resourceful circular city’ through the Short Term Scientific Missions (STSM) of the 2nd call with the topic of Circular Solutions in Reykjavik. The authors also acknowledge the support of the SORPA facility for providing the real data of waste management and for its interest. The authors especially appreciate the contribution of Thorleifur Thorbjornsson and Bjarni Hjardar.

Packaging is fundamental for food preservation and transportation but generates an environmental burden from its production and end-of-life management. This review evaluates packaging contribution to the environmental performance of seafood products. Life cycle assessment (LCA) studies were evaluated by both qualitative and quantitative analysis. The qualitative analysis assessed how direct (e.g., packaging material) and indirect impacts (e.g., influence on seafood loss and waste) have been considered, while the quantitative analysis evaluated packaging contribution to products? weight and climate change impact. Qualitative analysis revealed that seafood LCAs focus mainly on direct environmental impacts arising from packaging materials, for which some articles conducted sensitivity analysis to assess materials substitution. Recycling was found to be the most common recommendation to diminish direct potential environmental impacts arising from packaging end-of-life. However, standardized recovery rates and other end-of-life options (e.g., reuse), should be considered. Quantitative analysis revealed that cans' production contributes significantly to the overall climate change impact for canned products. On average, it contributes to 42% of a product's climate change impact and 27% of a product's weight. Packaging has a lower contribution when considering freezing, chilling, and other post-harvesting processing. It represents on average less than 5% of a product's climate change impact (less than 1 kg CO2 eq/kg) and 6% of a product's weight. Packaging material production is more relevant to aluminum, tinplate, and glass than for plastic and paper. Therefore, it is essential to accurately include these materials and their associated processes in inventories to improve the environmental assessment of seafood products.

While some papers report an increased risk of COVID-19 and worse outcomes1 in oncological patients, others have found no differences2 . We are not aware of studies assessing risk for COVID-19 and clinical outcomes of patients with Primary Cutaneous Lymphomas (PCL).

Laboratory practical sessions are critical to scientific training in biology but usually fail to promote logical and hypothesis-driven reasoning and rely heavily on the teacher's instructions. This paper describes a 2-day laboratory practicum in which students prepare and analyze larval cuticle preparations of Drosophila segmentation gene mutant strains. Embryonic segmentation involves three major classes of genes according to their loss-of-function phenotypes: the establishment of broad regions by gap genes, the specification of the segments by the pair-rule genes, and the compartments within segments by the segment polarity genes. Students are asked to sort undefined segmentation mutants into gap, pair-rule, or segment polarity categories based on their knowledge of the Drosophila segmentation process and the microscopic anatomical traits they are capable of finding in the sample preparations. This technically simple practicum prompts students to pay attention to detailed observation to detect anatomic markers of intrasegmental compartments and thorax versus abdomen cuticle, and promote their logical reasoning in hypothesizing to which segmentation type a given mutant fits best.

In the context of the COVID-19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID-19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS-CoV-2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow-up of the ophthalmic diseases. With this update (5(th)) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID-19 pandemic.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion. Jaarsma, T (corresponding author), Univ Linkoping, Fac Hlth Sci, Kungsgatan 40, S-60174 Norrkoping, Sweden. tiny.jaarsma@liu.se

An important goal of empirical demand analysis is choice and welfare prediction on counterfactual budget sets arising from potential policy interventions. Such predictions are more credible when made without arbitrary functional‐form/distributional assumptions, and instead based solely on economic rationality, that is, that choice is consistent with utility maximization by a heterogeneous population. This paper investigates nonparametric economic rationality in the empirically important context of binary choice. We show that under general unobserved heterogeneity, economic rationality is equivalent to a pair of Slutsky‐like shape restrictions on choice‐probability functions. The forms of these restrictions differ from Slutsky inequalities for continuous goods. Unlike McFadden–Richter's stochastic revealed preference, our shape restrictions (a) are global, that is, their forms do not depend on which and how many budget sets are observed, (b) are closed form, hence easy to impose on parametric/semi/nonparametric models in practical applications, and (c) provide computationally simple, theory‐consistent bounds on demand and welfare predictions on counterfactual budge sets.

International audience; Despite increasing awareness of issues affecting inclusivity, equity and diversity, change has been slow in science and academia, and gender disparities remain significant. Biogeography has not escaped this pattern. Here, we present a virtual issue compiling some of the most cited papers led by women that have been published in the Journal of Biogeography since 2009 in an effort to equalize visibility of women's influential work. We summarize leading gender disparities and their potential underlying causes, and present our motivation and methodology in compiling this issue. We further provide a blog, website and social media links to highlight the research of the authors whose work is showcased here. Highlighting influential contributions by women biogeographers is a small step towards equalizing visibility across genders. We hope that this virtual issue will also contribute in some way to creating a greater sense of belonging for women biogeographers.

This paper examines the relation between political connections and informed trading by corporate insiders in the context of the Financial Crisis. The unprecedented magnitude of government intervention, the substantial impact of this intervention on firm value, and the political nature of the intervention provide a powerful setting to examine the relation between political connections and informed trading. Consistent with political connections providing corporate insiders with an information advantage, we find strong evidence of a relation between political connections and the informativeness of their trades. Consistent with this relation stemming from private information related to government intervention, we find the relation is strongest during the period in which TARP funds were dispersed, and strongest among politically connected insiders at banks that received TARP funds. Examining insider trades around the announcements of TARP infusions, we find evidence of significant trading thirty days in advance of the announcement, and that these trades predict the market reaction to the announcement. Notably, we find these relations are present only for the trades of politically connected insiders. Overall, our results suggest that politically connected insiders had an information advantage during the Crisis and traded to exploit this advantage.

When we blame one another for moral transgressions, we are doing something: we accuse the other of wrongdoing (“You did this on purpose”), demand an explanation (“How could you?”,“What were you thinking?”), or request an apology or compensation (“You owe me a drink!”). ese speech acts, in turn, invite characteristic responses – explanations, excuses, justifications, apologies – and render others inappropriate. Blame can be public, when spoken out loud, or private, when merely thought. is suggests that there is a moral practice of blaming that we frequently engage in – a socially recognized activity structured by internal norms. My aim in this paper is to investigate its nature.

This research surveys changing attitudes to drawing pedagogy, in the context of digitisation, moves toward student-centred learning in Art and Design Higher Education, and anecdotal reports of declining competence. Based on student, teacher and examiner’s experiences, it has been possible to gain insights into how drawing instruction has changed over the past generation. This paper examines the attitudes, values and concerns of students and educators regarding drawing instruction. The study reveals that, in the UK, drawing skills are considered to be gradually declining, while traditional notions of skill are called into question. Drawing as a means of visual recording, representation and communication remains valued, although no longer essential as it once was; while drawing to augment thought process, is increasingly recognised as an integral skill which enables innovation. The latter is rarely ‘taught’ but relies on core competencies that many lecturers fear are being eroded. Increasing value is placed on drawing ‘as process’, while provision is moving towards individualised instruction requiring students to work independently. While new technologies are a factor, this paper re-frames the issue as an imbalance between creative outcomes and creative process, with a disparity between school and university levels. This paper calls for a renewed emphasis on ‘drawing as process’ as preparation for university, and for further consideration of the core competencies underpinning the use of drawing as a tool of thought, and how these might be standardised.

One of the most used painkillers is acetaminophen (APAP), which is safe at the right dose. However, several studies have described populations susceptible to APAP-induced liver damage, mainly in livers with steatosis. Thus, clinicians should consider the presence of obesity and other chronic liver diseases like nonalcoholic fatty liver disease (NAFLD) when indicating treatment with APAP. Liver damage from this drug is generated through its metabolite N-acetyl-p-benzoquinone imine, which is detoxified with glutathione (GSH). Prior depletion of GSH in steatotic hepatocytes plays a key role in APAP-induced hepatotoxicity in people with obesity and NAFLD. The knowledge about the damage to the liver or APAP in susceptible people like the obese and those with NAFLD is of great relevance for the sanitary sector because it would imply strategies of different therapeutic approach in such patients. This paper reviews the role of APAP in liver damage in the presence of obesity, NAFLD, and nonalcoholic steatohepatitis.

Recently, young COVID-19 patients have presented with erythematous and purpuric acral lesions similar to chilblains(1–3). Despite the scarcity of published cases, this topic has attracted significant mass media attention.(4) Dermatologists have noted that more people than would be expected at this time of year are seeking medical attention for these chilblain-like lesions. Some have suggested that people presenting with this manifestation should be tested and isolated(2). Determining the accuracy of this association is therefore crucial. To establish the real prevalence of COVID-19 in patients with acral skin lesions, we firstly evaluated all the cases of acral lesions presented in dermatology and paediatrics departments and family doctors’ offices in an eastern Spanish region over a three-week period. Then we prospectively performed a SARS-CoV-2 PCR on nasopharyngeal aspirates taken from all available patients to determine whether their cutaneous manifestations were predictive of a positive result. To put our findings into context, we reviewed all the articles published before May 2020 concerning COVID-19 patients with cutaneous lesions. We evaluated 58 patients, whose characteristics are summarized in Table 1. In most cases, lesions were chilblain-like. Fifteen patients had already been tested, and only one had a positive result: an 85-year-old man admitted for severe Covid-19 pneumonia. He had an ulcer on a toe that was finally determined to be vascular in nature. We performed prospective PCR testing in 24 patients. All test results were negative. In total, then, PCR was negative in 38 patients and positive in a single patient whose lesion was very unlikely to be due to COVID-19. Our bibliography search returned 97 articles and we found 2 more through cross-references. Nine of these articles dealt with acral lesions specifically. Their results are summarized in Table 2. Data published in the literature are heterogeneous, as are the methods employed to collect them. The first papers looked at cutaneous manifestations in patients with confirmed SARS-CoV-2 infection.(5–8) This approach cannot reveal whether this dermatologic manifestation is a specific marker of SARS-CoV-2 infection, since patients without COVID-19 are not included. The other approach, which we have followed, is to analyse all patients with acral lesions. This can be done retrospectively, reporting on patients in the sample who have already been tested, or prospectively, performing the test on all available patients, regardless of whether they have symptoms. The retrospective method has a significant risk of confounding bias: due to the scarcity of COVID-19 tests(8), they are usually reserved for patients with COVID-19-related symptoms, who are obviously more likely to test positive. All previous studies including only patients with cutaneous acral lesions (summarized in table 2) have been retrospective, and only a minority of patients were tested. In total, 12 out of at least 49 tested patients were positive (24.5%). Combined with our results, they total 13 positives out of 88 tests (14.8%). There are two possible explanations for the high proportion of negative results: I) A high number of false negatives. II) The lesions are not related to SARS-CoV-2 infection. The low prevalence of an infected contact in our sample, after three weeks of strict confinement in Spain, makes the possibility of being infected in our cohort less likely. The diffusion of this entity by the mass media may have caused patients who would not normally consult to do so.(9) . Other possible explanations include a concomitant parvovirus B19 outbreak(10) or trauma-induced lesions. Our study suggests that acral skin lesions are not a specific marker of SARS-CoV-2 infection. Although larger prospective studies are needed, current evidence indicates that acral skin lesions should not be regarded as a sign of COVID-19 in otherwise asymptomatic patients.

Diabetes and metabolic syndrome are associated with the typical American high glycemia diet and result in accumulation of high levels of advanced glycation end products (AGEs), particularly upon aging. AGEs form when sugars or their metabolites react with proteins. Associated with a myriad of age‐related diseases, AGEs accumulate in many tissues and are cytotoxic. To date, efforts to limit glycation pharmacologically have failed in human trials. Thus, it is crucial to identify systems that remove AGEs, but such research is scanty. Here, we determined if and how AGEs might be cleared by autophagy. Our in vivo mouse and C. elegans models, in which we altered proteolysis or glycative burden, as well as experiments in five types of cells, revealed more than six criteria indicating that p62‐dependent autophagy is a conserved pathway that plays a critical role in the removal of AGEs. Activation of autophagic removal of AGEs requires p62, and blocking this pathway results in accumulation of AGEs and compromised viability. Deficiency of p62 accelerates accumulation of AGEs in soluble and insoluble fractions. p62 itself is subject to glycative inactivation and accumulates as high mass species. Accumulation of p62 in retinal pigment epithelium is reversed by switching to a lower glycemia diet. Since diminution of glycative damage is associated with reduced risk for age‐related diseases, including age‐related macular degeneration, cardiovascular disease, diabetes, Alzheimer's, and Parkinson's, discovery of methods to limit AGEs or enhance p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies., AGEs are toxic compounds formed by non‐enzymatic reactions between sugars and proteins. AGEs are prone to aggregate. Insoluble AGEs are efficiently removed via p62‐selective autophagy. The autophagic removal of AGEs is a conserved pathway, and the lack of p62 leads to accumulation of toxic AGEs in mouse and worms. Enhanced autophagy is protective against glycation‐derived damage. p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies.

Background During the SARS-CoV2 pandemic, there has been increase in hyperinflammatory presentation in previously healthy children with a variety of cardiac manifestations. Our objective is to describe the cardiac manifestations found in an international cohort of 55 pediatric cases with multi-system inflammatory syndrome (MIS-C) during the SARS-CoV2 pandemic. Methods and Results We reviewed data on previously healthy pediatric patients (=18 years) with structurally normal hearts who presented at hospitals in the United States, United Kingdom, Spain and Pakistan with MIS-C and had consultation with a pediatric cardiologist. Data collected included demographics, clinical presentation, laboratory values, electrocardiographic abnormalities, echocardiographic findings and initial therapies. A total of 55 patients presented with MIS-C. Thirty-five patients (64%) had evidence of decreased left ventricular function, 17 (31%) had valvulitis, 12 (22%) with pericardial effusion and 11 (20%) with coronary abnormalities. Twenty-seven (49%) required ICU admission and 24 (44%) had evidence of shock. Eleven patients (20%) fulfilled complete Kawasaki disease criteria and had lower NT pro-BNP, D-dimer and ferritin levels compared with those who did not fulfill criteria. Electrophysiologic abnormalities occurred in 6 patients and included complete atrioventricular (AV) block, transient AV block and ventricular tachycardia. Conclusions We describe the first international cohort of pediatric patients with MIS-C during the SARS-CoV2 pandemic with a range of cardiac manifestations. This paper brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow-up.

The co‐occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre‐clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time., We describe the co‐occurrence of cancer and heart failure (HF), their potential shared risk factors, and their pathophysiological mechanisms. We advocate intense interaction between cardiologists and oncologists to achieve unifying hypotheses and collaborative pre‐clinical and clinical studies.

Particle image velocimetry (PIV), or digital image correlation (DIC), is a widely used technique tomeasure soil displacements and strains in small-scale geotechnical models. Arrays of single-board computers (SBCs) produced by Raspberry Pi, and their associated 8-MP cameras, are being used at the University of Cambridge to capture the images required for DIC analysis. This alternative to more expensive camera set-ups has numerous advantages. A single expensive and large camera can be replaced—at low cost—by multiple cameras, adding flexibility and affordability to any experimental set-up. Traditionally, the alignment of multiple cameras to each other and the referencing to a known coordinate system required painted or machined markers to be located on the observation windows through which the experiments are viewed. This can obstruct localised soil grain displacement measurements in those areas of the model where such markers are placed. To complement the Raspberry Pi camera system, a markerless calibration method was used during image acquisition. This paper outlines the set-up of four of these small computers and associated cameras, provides an overview of the use of themarkerless referencing system and reviews two different experimental apparatus used tomeasure soil displacement and strain.When the cost of additional cabling, connectors and mounting hardware is considered for this system, the total cost to implement was approximately $125 USD per camera plus one-time costs of $175 USD for system peripherals, which represents outstanding value and enables practically all geotechnical laboratories to develop similar capabilities.

The Neurovisceral Integration Model (NIM) is one of the most influential psychophysiological models addressing the interplay between the autonomic (ANS) and central nervous system (CNS). In their groundbreaking conceptual work, integrating autonomic, attentional, and affective systems into a functional and structural network, Thayer & Lane laid the foundation for empirical research in the past two decades. The present paper provides a principal outline aiming to reflect and further elaborate on the model from a dynamic developmental perspective. The central question at hand is, how does neurovisceral integration develop (early in life)? By reviewing the existing evidence, it is illustrated that key components of the model, both, on a physiological and psychological level, undergo extensive change early in the course of life. This sensitive period of human development seems key for our understanding of the integrated action of the ANS and CNS in emotion across the lifespan. Early life events may interfere with the fine-tuned interplay of this shared neural circuitry resulting in long-term dysfunction and psychiatric illness. In the absence of longitudinal data covering the entire co-development of the ANS and CNS from early childhood to adolescence into early adulthood, it is suggested, that vagal activity and its normative increase in adolescence is a key premise for normative brain development on a structural and functional level, subsequent psychological functioning and adaptive regulation. Implications from this dynamic perspective and suggestions for future research in the field of developmental psychophysiology are discussed.

Horizontal gene transfer (HGT) is widespread among prokaryotes driving their evolution. In this paper, we review the potential impact in humans of the HGT between prokaryotes living in close association with humans in two scenarios: horizontal transfer in human microbiomes and transfer between microbes living in human managed environments. Although our vision is focused on the possible impact of these transfers in the propagation of antibiotic resistance genes or pathogenicity determinants, we also discuss possible human physiological adaptations via gene transfer between resident and occasional bacteria in the human microbiome., The authors thank the two anonymous referees for their valuable comments. LB is supported by the grant CGL2016-75262-P of Spain DGI. RP is supported by a postdoctoral contract (Submodality 5.2.A) funded by the Research Plan of the University of Cordoba.

Chemical communication plays an essential role in several social and reproductive behaviors of many animals. In lizards, the main sources of semiochemicals are femoral or pre-anal gland secretions and feces. In male lizards Psammodromus algirus, there are age-related differences in the chemical composition of femoral gland secretions and in the reproductive strategies, with older males defending territories and females, while younger males adopting sneak-mating strategies. Females flee more often from mating advances of young males than from those of old males, which are more successful in obtaining matings. This suggests that age discrimination of males may be important for females. We tested here whether females showed differential chemosensory responses to chemical cues (femoral gland secretion and feces) of males of two age classes, and whether females use information from substrate scent marks of males of different ages to select where to stay. We found that females elicited more tongue-flicks to the secretion and feces of old males than to control or secretion and feces of young males. Also, the time spent by females on a scented paper depended on the treatment, suggesting that females tended to spend more time on scent marks made with femoral secretions of old males. Adult females seemed capable to discriminate between young and old males based on chemical cues alone and showed more interest in scents of old males. However, substrate scent marks did not seem to entirely determine site selection by females, suggesting that females might need additional cues to perform the choice. These results can be explained by the different age-dependent reproductive strategies of males, which can affect differentially to females., Financial support was provided by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2017/19640‐0) and by the Ministerio de Economía y Competitividad project MINECO CGL2014‐53523‐P.

This essay considers why Jewish antiquity largely fell outside the purview of ancient historians in the Germanies for over half a century, between 1820 and 1880, and examines the nature of those portraits that did, in fact, arise. To do so, it interrogates discussions of Jewish antiquity in this half century against the background of those political and national values that were consolidating across the German states. Ultimately, the paper claims ancient Jewish history did not provide a compelling model for the dominant (Protestant) German scholars of the age, which then prompted the decline of antique Judaism as a field of interest. This investigation into the political and national dimensions of ancient history both supplements previous lines of inquiry and complicates accounts that assign too much explanatory power to a regnant anti-Judaism or anti-Semitism in the period and place. Firstly, the analysis considers those reasons why so little attention was granted to Jewish history by ancient historians in the first place, as opposed to its relative prominence before ca. 1820. Second, the essay examines representations of ancient Judaism as fashioned by those historians who did consider the subject in this period. Surveying works composed not only for the upper echelons of scholarship but also for adolescents, women, and the laity, it scrutinizes a series of arguments advanced and assumptions embedded in universal histories, histories of the ancient world, textbooks of history, and dedicated histories to either Greece or Rome. Finally, the paper asserts the Jewish past did not conform to the values of cultural ascendancy, political autonomy, national identity, and religious liberty increasingly hallowed across the Germanies of the 19th century, on the one hand, and inscribed into the very enterprise of historiography, on the other. The perceived national and political failures of ancient Jews – alongside the ethnic or religious ones discerned by others – thus made antique Judaism an unattractive object of study in this period.

The discovery of a rare fly in a North London cemetery marks my entry point into a wider reflection on the value and significance of urban biodiversity. Using different indices of ecological endangerment, along with a critical reading of new materialist insights, this paper explores the cultural, political, and scientific significance of saproxylic (rotten wood) invertebrate communities in an urban context. The paper brings the fields of urban ecology and post-humanism into closer dialogue to illuminate aspects to urban nature that have not been systematically explored within existing analytical frameworks. We consider a series of intersecting worlds, both human and non-human, as part of a glimpse into saproxylic dimensions to urban nature under a putative transition to a new geo-environmental epoch., European Research Council

Although the notion that HRM activities are necessary conditions for achieving certain outcomes is widespread in HRM research, most empirical studies follow an additive sufficiency logic. That is, they analyse whether HRM activities increase an outcome, assuming that they can compensate for one another. However, this does not correspond to the idea of necessity where single HRM activities are required for an outcome to occur and cannot be compensated when absent. We discuss the differences between sufficiency and necessity logics in terms of theory, methodology, and practical relevance. Also, we suggest using a new approach and analysis technique in HRM research: necessary condition analysis. We illustrate the application of the method by analysing data on the relationship between ability‐, motivation‐, and opportunity‐enhancing HRM practices (i.e., high‐performance work practices) and employee performance. This illustrative example highlights that necessary conditions require particular theoretical attention and suitable empirical methods. The paper concludes by showing the value of studying necessary conditions, because such analyses allow straightforward recommendations to be given of high relevance for HRM practice, which differ from and add to recommendations based on additive sufficiency logic and analyses.

A comparative study on the self‐assembly of sexiphenyl‐dicarbonitrile on highly oriented pyrolytic graphite and single‐layer graphene on Cu(111) is presented. Despite an overall low molecule–substrate interaction, the close‐packed structures exhibit a peculiar shift repeating every four to five molecules. This shift has hitherto not been reported for similar systems and is hence a unique feature induced by the graphitic substrates.

1. In a previous series of papers (Sutherland et al., 2018), we summarise the use of a range of social science methods in conservation decision making. Moon et al. (submitted) claim that the special issue risks narrowing the scope of social science research and suggest that we presented a limited perspective on the field. They thereby criticise the special issue for not doing something that it never intended to do in the first instance. We did not claim that the list of articles covered in the special issue is a comprehensive list (which it obviously is not) and we are unclear why anyone would think it is. 2. While we consider the Moon et al. (submitted) paper to be a useful contribution for conservation scientists as a supplementary paper, it serves less as a critique to the special issue. Moon et al.’s (submitted) paper makes very few direct and substantive criticisms of points raised in the special issue. We respond to areas of contention referring specifically to research philosophy, bias, and data reporting. 3. Moon et al. (submitted) criticise the set of papers for perpetuating an objectivist view of the world. We believe that it would be rather disconcerting for the research community if there were no social truths to discover. Rather, social science research methods conducted in specific places can be good ways of exploring how truths vary in different contexts. 4. We also note that Moon et al. (submitted) completely missed the point we were trying to make about psychological biases, which are quite different to the issues associated with researcher bias highlighted by them. 5. We encourage readers to pay close attention to the use of social science methods in conservation science. We reiterate, however, that the main purpose of the special issue was to ensure that social science methodologies for decision making are accessible for all conservation scientists to use, regardless of disciplinary background.

This paper investigates whether maintaining a reputation for consistently beating analysts’ earnings expectations can motivate executives to move from “within GAAP” earnings management to “outside of GAAP” earnings manipulation. We analyze firms subject to SEC enforcement actions and find that these firms consistently beat analysts’ quarterly earnings forecasts in the three years prior to the manipulation period and continue to do so by smaller “beats” during the manipulation period. We find that manipulating firms beat expectations around 86 percent of the time in the twelve quarters prior to the manipulation period (versus 75 percent for control firms) and that manipulation often ends with a miss in expectations. We document that executives of manipulating firms face strong stock market and CEO pressure to perform. Prior to the manipulation period, these firms have high analyst optimism, growing institutional interest, and high market valuations, along with powerful CEOs. Further, we find that maintaining a reputation for beating expectations is more important than CEO overconfidence and is incremental to CEO equity incentives for explaining manipulation. Our results suggest that pressure to maintain a reputation for beating analysts’ expectations can encourage aggressive accounting and, ultimately, earnings manipulation.

The solution of a structure of human Rab27a suffering from severe anisotropy and translational noncrystallographic symmetry was aided by identifying diffraction measurements with low information content., Data pathologies caused by effects such as diffraction anisotropy and translational noncrystallographic symmetry (tNCS) can dramatically complicate the solution of the crystal structures of macromolecules. Such problems were encountered in determining the structure of a mutant form of Rab27a, a member of the Rab GTPases. Mutant Rab27a constructs that crystallize in the free form were designed for use in the discovery of drugs to reduce primary tumour invasiveness and metastasis. One construct, hRab27aMut, crystallized within 24 h and diffracted to 2.82 Å resolution, with a unit cell possessing room for a large number of protein copies. Initial efforts to solve the structure using molecular replacement by Phaser were not successful. Analysis of the data set revealed that the crystals suffered from both extreme anisotropy and strong tNCS. As a result, large numbers of reflections had estimated standard deviations that were much larger than their measured intensities and their expected intensities, revealing problems with the use of such data at the time in Phaser. By eliminating extremely weak reflections with the largest combined effects of anisotropy and tNCS, these problems could be avoided, allowing a molecular-replacement solution to be found. The lessons that were learned in solving this structure have guided improvements in the numerical analysis used in Phaser, particularly in identifying diffraction measurements that convey very little information content. The calculation of information content could also be applied as an alternative to ellipsoidal truncation. The post-mortem analysis also revealed an oversight in accounting for measurement errors in the fast rotation function. While the crystal of mutant Rab27a is not amenable to drug screening, the structure can guide new modifications to obtain more suitable crystal forms.

Over two decades, the checklist has risen to prominence in healthcare improvement. This paper contributes to the debate between its proponents and critics, making the case for an STS-informed understanding of the checklist that demonstrates the limitations of both the ‘checklist-as-panacea’ and ‘checklist-as-socially-determined’ positions. Attending to the checklist as a socio-material object endowed with affordances that call upon clinicians to act (Hutchby 2001, Allen 2012), the study revisits the efforts of a recent improvement initiative, the Enhanced Peri-Operative Care for High-risk patients (EPOCH) trial. Rather than a singularised simple tool, this study discusses four different and relationally enacted logics of the checklist as a stop and check tool, a clinical prompt, an audit tool, and a clinical record. Each logic is associated with specific temporality, beneficiaries, relationship to material forms, and interpellates (Law 2002) clinicians to initiate specific actions which can conflict. The paper seeks to make the case for intervention to improve such tools and consciously account for the consequences of their design and materiality and calls for supporting such settings and arrangements in which incoherences collected in tools can be locally negotiated.

OBJECTIVE: The collection and use of ordinal variables are common in many psychological and psychiatric studies. Although the models for continuous variables have similarities to those for ordinal variables, there are advantages when a model developed for modeling ordinal data is used such as avoiding "floor" and "ceiling" effects and avoiding to assign scores, as it happens in continuous models, which can produce results sensitive to the score assigned. This paper introduces and focuses on the application of the ordered stereotype model, which was developed for modeling ordinal outcomes and is not so popular as other models such as linear regression and proportional odds models. This paper aims to compare the performance of the ordered stereotype model with other more commonly used models among researchers and practitioners. METHODS: This article compares the performance of the stereotype model against the proportional odd and linear regression models, with three, four, and five levels of ordinal categories and sample sizes 100, 500, and 1000. This paper also discusses the problem of treating ordinal responses as continuous using a simulation study. The trend odds model is also presented in the application. RESULTS: Three types of models were fitted in one real-life example, including ordered stereotype, proportional odds, and trend odds models. They reached similar conclusions in terms of the significance of covariates. The simulation study evaluated the performance of the ordered stereotype model under four cases. The performance varies depending on the scenarios. CONCLUSIONS: The method presented can be applied to several areas of psychiatry dealing with ordinal outcomes. One of the main advantages of this model is that it breaks with the assumption of levels of the ordinal response are equally spaced, which might be not true.

The Galileo E6 band operates at a nonprimary frequency band within the L-band. This presents challenging situations in the vicinity of other, legitimate, radiolocation services. This is the case for Air Traffic Control (ATC) radar, which is seen as an in-band–pulsed interference by a GNSS receiver. This paper provides a detailed study of the impact of such interference, as well as localization approaches. Particularly, the paper describes the ATC jamming event captured on a GNSS permanent station, its effects on a real receiver, and how it was tracked to localize the source of interference. An ultra low-cost array-based solution is prototyped, based on commercial off-the-shelf devices, that implements a two-element array. Experimental results are shown and discussed using real data, validating the localization performance of the prototype. © 2019 Institute of Navigation

To help prevent anaemia, it is a requisite for blood donors to undergo a haemoglobin test to ensure levels are not too low before donation. It is therefore important to have an accurate testing device and strategy to ensure donors are not being inappropriately bled. A recent study in blood donors used a selective testing strategy where if a donor’s haemoglobin level is below the level required for donation, then another reading is taken and if this occurs again, a third and final reading is used. This strategy can reduce the average number of readings required per donor compared to taking three measurements for all donors. However, the final decision-making measurement will on average be higher than a single measurement. In this paper, a selective testing strategy is compared against other strategies. Individual-level biases are derived for the selective strategy and are shown to depend on how close a donor’s true haemoglobin level is to the donation threshold and the magnitude of error in the testing device. A simulation study was conducted using the distribution of haemoglobin levels from a large donor population to investigate the effects different strategies have on population performance. We consider scenarios based on varying the measurement device bias and error, including differential biases that depend on the underlying haemoglobin level. Discriminatory performance is shown to be affected when using the selective testing strategies, especially when measurement error is large and when differential bias is present in the device. We recommend that the average of a number of readings should be used in preference to selective testing strategies if multiple measurements are available.

Part of the debate about the ‘productivity puzzle’ concerns potential mismeasurement of GDP due to digital activities. This paper discusses some measurement issues arising from digitally-enabled substitutions in activity across the conventional production boundary. Production boundary issues are not new, as conventionally defined GDP statistics account for the monetary cost but not the time cost of consumption and production. This means changes in the way time is allocated between market and home production affect measured growth and productivity. Just as technological innovation in domestic appliances led to a substitution from home production into market consumption in the second half of the 20th century, today’s digital innovations are driving some reverse substitution out of the market into home production. Statistical agencies do not currently collect the data needed to measure the scale of the switch, but the available evidence suggests it may be enough to make a contribution to understanding the puzzling behaviour of measured productivity

AIM: To identify the gait parameters used to assess gait disorders in children with bilateral spastic cerebral palsy (CP) and evaluate their responsiveness to treatments. METHOD: A systematic search within PubMed, Web of Science, and Scopus (in English, 2000-2016) for randomized controlled trials of children with bilateral spastic CP who were assessed by instrumented gait analysis (IGA) was performed. Data related to participants and study characteristics, risk of bias, and outcome measures were collected. A list of gait parameters responsive to clinical interventions was obtained. RESULTS: Twenty-one articles met the inclusion criteria. Eighty-nine gait parameters were identified, 56 of which showed responsiveness to treatments. Spatiotemporal and kinematic parameters were widely used compared to kinetic and surface electromyography data. The majority of responsive gait parameters were joint angles at the sagittal plane (flexion-extension). INTERPRETATION: The IGA yields responsive outcome measures for the gait assessment of children with bilateral spastic CP. Spatiotemporal and kinematic (at sagittal plane) parameters are the gait parameters used most frequently. Further research is needed to establish the relevant gait parameters for each clinical problem. WHAT THIS PAPER ADDS: Fifty-six responsive gait parameters for children with bilateral spastic cerebral palsy were identified. Most responsive gait parameters belong to joint angles time-series at sagittal plane. Spatiotemporal and kinematic parameters are widely used compared to kinetic and surface electromyography parameters.

This paper investigates the determinants of internal mobility across Spanish provinces of both foreigners and natives over the decade 2004-14. Building on an extended gravity model, our econometric strategy controls for multilateral resistance to migration by including different fixed effects structures. Additionally, the paper allows for some nonlinearities in the key economic determinants of migration, wages and unemployment. The main finding is that the impact of economic factors on internal migration is higher for foreigners than for natives; furthermore, the effect of these factors on internal migration is clearly nonlinear for the group of natives, while this only happens for foreigners when dyadic fixed effects of origin-destination are considered. Finally, the paper shows that the nature of the amenities with the greatest impact on internal movements differs between the two groups: foreigners look for social services and cultural amenities, whereas natives are more attracted by good climate conditions.

We study the upscaling and prediction of large-scale solute dispersion in heterogeneous porous media with focus on preasymptotic or anomalous features such as tailing in breakthrough curves and spatial concentration profiles as well as nonlinear evolution of the spatial variance of the concentration distribution. Spatial heterogeneity in the hydraulic medium properties is represented in a stochastic modeling approach. Direct numerical Monte Carlo simulations of flow and advective particle motion combined with a Markov model for streamwise particle velocities give insight in the mechanisms of preasymptotic and asymptotic solute transport in terms of the statistical signatures of the medium and flow heterogeneity. Based on the representation of equidistantly sampled particle velocities as a Markov process, we derive an upscaled continuous time random walk approach that can be conditioned on the flow velocities and thus hydraulic conductivity in the injection region. In this modeling framework, we identify the Eulerian velocity distribution, advective tortuosity, and the correlation length of particle velocities as the key quantities for large-scale transport prediction. Thus, the upscaled model predicts the spatial concentration profiles, their first and second centered moments, and the breakthrough curves obtained from direct numerical Monte Carlo simulations in spatially heterogeneous conductivity fields. The presented approach allows to relate the medium and flow properties to large-scale preasymptotic and asymptotic solute dispersion. ©2019. American Geophysical Union. All Rights Reserved., The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007‐2013) ERC Grant Agreement 617511 (MHetScale). The data presented in the paper can be accessed at the GitLab ( https://gitlab.com/marco.dentz/darcy‐simulations‐data ).

Horizontal gene transfer (HGT) is widespread among prokaryotes driving their evolution. In this paper, we review the potential impact in humans of the HGT between prokaryotes living in close association with humans in two scenarios: horizontal transfer in human microbiomes and transfer between microbes living in human managed environments. Although our vision is focused on the possible impact of these transfers in the propagation of antibiotic resistance genes or pathogenicity determinants, we also discuss possible human physiological adaptations via gene transfer between resident and occasional bacteria in the human microbiome. The authors thank the two anonymous referees for their valuable comments. LB is supported by the grant CGL2016-75262-P of Spain DGI. RP is supported by a postdoctoral contract (Submodality 5.2.A) funded by the Research Plan of the University of Cordoba.