A Lesson from COVID-19 in the Importance of Sex Disaggregated Data: Sex Differences in SARS-CoV-2 Infection and Mortality Rates

Background: Emerging surveillance data from the COVID 19 pandemic suggest better outcomes in women. Objective: This analysis aims to determine the magnitude of sex differences in SARS-CoV-2 infection rates and survival at a country level. Methods: Data was sourced from the Global Health 50/50 (GH 50/50) website https://globalhealth5050.org/covid19, housed at University College of London, which collects government reported national surveillance data on confirmed cases of COVID 19 and confirmed deaths. This analysis used data completely disaggregated by sex, cutoff date 5/8/2020. Results: Of 78 countries, with 3,044,513 confirmed cases of COVID 19 and 181,742 deaths, data were completely disaggregated by sex in 36 countries, partially disaggregated in 26, and not disaggregated in 16. In countries, with completely disaggregated data, 1,240, 803 cases of COVID-19 were reported on May 3, 4, 5 or 6, 2020 in 31 countries, and between Feb 28 and April 28 in 5 countries. The average proportion of cases in women was 50.3%: range 22% (Pakistan) to 63% (Netherlands). Deaths were reported in 83,388 individuals. The mean proportion of deaths in women was 39.2% (range 20% to 53%). The mean ratio of deaths (men to women) was 1.62 (range 0.9 to 3.2). Discussion: This analysis of surveillance data from 36 countries shows a sex difference in mortality from COVID-19, with men more likely to die than women. Possible explanations include sex differences in the immune system, gender differences in environmental exposures or access to healthcare, and differences in comorbidities. Additional research to assess potential causes, and collect and analyze data by age, race, and ethnicity as well as sex and gender would be of value. These observations highlight the importance of disaggregating data by sex and gender in order to understand disease susceptibility, prevalence, and outcomes.https://jdc.jefferson.edu/sexandgenderhealth/1017/thumbnail.jp

Uncovering the overlapping community structure of complex networks in nature and society

Many complex systems in nature and society can be described in terms of networks capturing the intricate web of connections among the units they are made of. A key question is how to interpret the global organization of such networks as the coexistence of their structural subunits (communities) associated with more highly interconnected parts. Identifying these a priori unknown building blocks (such as functionally related proteins, industrial sectors and groups of people) is crucial to the understanding of the structural and functional properties of networks. The existing deterministic methods used for large networks find separated communities, whereas most of the actual networks are made of highly overlapping cohesive groups of nodes. Here we introduce an approach to analysing the main statistical features of the interwoven sets of overlapping communities that makes a step towards uncovering the modular structure of complex systems. After defining a set of new characteristic quantities for the statistics of communities, we apply an efficient technique for exploring overlapping communities on a large scale. We find that overlaps are significant, and the distributions we introduce reveal universal features of networks. Our studies of collaboration, word-association and protein interaction graphs show that the web of communities has non-trivial correlations and specific scaling properties.Comment: The free academic research software, CFinder, used for the publication is available at the website of the publication: http://angel.elte.hu/clusterin

Which activities threaten independent living of elderly when becoming problematic : inspiration for meaningful service robot functionality

Purpose: In light of the increasing elderly population and the growing demand for home care, the potential of robot support is given increasing attention. In this paper, an inventory of activities was made that threaten independent living of elderly when becoming problematic. Results will guide the further development of an existing service robot, the Care-O-bot®. Method: A systematic literature search of PubMed was performed, focused on the risk factors for institutionalization. Additionally, focus group sessions were conducted in the Netherlands, United Kingdom and France. In these focus group sessions, problematic activities threatening the independence of elderly people were discussed. Three separate target groups were included in the focus group sessions: (1) elderly persons (n = 41), (2) formal caregivers (n = 40) and (3) informal caregivers (n = 32). Results: Activities within the International Classification of Functioning domains mobility, self-care, and interpersonal interaction and relationships were found to be the most problematic. Conclusions: A distinct set of daily activities was identified that may threaten independent living, but no single activity could be selected as the main activity causing a loss of independence as it is often a combination of problematic activities that is person-specific. Supporting the problematic activities need not involve a robotic solution Read More: http://informahealthcare.com/doi/abs/10.3109/17483107.2013.840861Peer reviewe

Global Networks of Trade and Bits

Considerable efforts have been made in recent years to produce detailed topologies of the Internet. Although Internet topology data have been brought to the attention of a wide and somewhat diverse audience of scholars, so far they have been overlooked by economists. In this paper, we suggest that such data could be effectively treated as a proxy to characterize the size of the "digital economy" at country level and outsourcing: thus, we analyse the topological structure of the network of trade in digital services (trade in bits) and compare it with that of the more traditional flow of manufactured goods across countries. To perform meaningful comparisons across networks with different characteristics, we define a stochastic benchmark for the number of connections among each country-pair, based on hypergeometric distribution. Original data are thus filtered by means of different thresholds, so that we only focus on the strongest links, i.e., statistically significant links. We find that trade in bits displays a sparser and less hierarchical network structure, which is more similar to trade in high-skill manufactured goods than total trade. Lastly, distance plays a more prominent role in shaping the network of international trade in physical goods than trade in digital services.Comment: 25 pages, 6 figure

Collaborative Enhancement of Antibody Binding to Distinct PECAM-1 Epitopes Modulates Endothelial Targeting

Antibodies to platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitate targeted drug delivery to endothelial cells by “vascular immunotargeting.” To define the targeting quantitatively, we investigated the endothelial binding of monoclonal antibodies (mAbs) to extracellular epitopes of PECAM-1. Surprisingly, we have found in human and mouse cell culture models that the endothelial binding of PECAM-directed mAbs and scFv therapeutic fusion protein is increased by co-administration of a paired mAb directed to an adjacent, yet distinct PECAM-1 epitope. This results in significant enhancement of functional activity of a PECAM-1-targeted scFv-thrombomodulin fusion protein generating therapeutic activated Protein C. The “collaborative enhancement” of mAb binding is affirmed in vivo, as manifested by enhanced pulmonary accumulation of intravenously administered radiolabeled PECAM-1 mAb when co-injected with an unlabeled paired mAb in mice. This is the first demonstration of a positive modulatory effect of endothelial binding and vascular immunotargeting provided by the simultaneous binding a paired mAb to adjacent distinct epitopes. The “collaborative enhancement” phenomenon provides a novel paradigm for optimizing the endothelial-targeted delivery of therapeutic agents

The frontiers of participatory public engagement

Currently missing from critical literature on public engagement with academic research is a public-centric analysis of the wider contemporary context of developments in the field of public engagement and participation. Drawing on three differently useful strands of the existing theoretical literature on the public, this article compares a diverse sample of 100 participatory public engagement initiatives in order to first, analyse a selection of the myriad ways that the public is being constituted and supported across this contemporary field and second, identify what socio-cultural researchers might learn from these developments. Emerging from this research is a preliminary map of the field of public engagement and participation. This map highlights relationships and divergences that exist among diverse forms of practice and brings into clearer view a set of tensions between different contemporary approaches to public engagement and participation. Two ‘frontiers’ of participatory public engagement that socio-cultural researchers should attend are also identified. At the first, scholars need to be critical regarding the particular versions of the public that their preferred approach to engagement and participation supports and concerning how their specific identifications with the public relate to those being addressed across the wider field. At the second frontier, researchers need to consider the possibilities for political intervention that public engagement and participation practice could open out, both in the settings they are already working and also in the much broader, rapidly developing and increasingly complicated contemporary field of public engagement and participation that this article explores

Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

FISH as an effective diagnostic tool for the management of challenging melanocytic lesions

<p>Abstract</p> <p>Background</p> <p>The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies can be classified as benign (nevus) or malignant (melanoma) using well-established histopathologic criteria, there exists a cohort for which the prediction of clinical behaviour and invasive or metastatic potential is difficult if not impossible to ascertain on the basis of morphological features alone. Multiple studies have shown that there is significant disagreement between pathologists and even expert dermatopathologists in the diagnosis of this subgroup of difficult melanocytic lesions.</p> <p>Methods</p> <p>A four probe FISH assay was utilized to analyse a cohort of 500 samples including 157 nevus, 176 dysplastic nevus and 167 melanoma specimens.</p> <p>Results</p> <p>Review of the lesions determined the assay identified genetic abnormalities in a total of 83.8% of melanomas, and 1.9% of nevus without atypia, while genetic abnormalities were identified in 6.3%, 6.7%, and 10.3% of nevus identified with mild, moderate and severe atypia, respectively.</p> <p>Conclusions</p> <p>Based on this study, inheritable genetic damage/instability identified by FISH testing is a hallmark of a progressive malignant process, and a valuable diagnostic tool for the identification of high risk lesions.</p