ResearchPad - network-analysis https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A network analysis of research productivity by country, discipline, and wealth]]> https://www.researchpad.co/article/elastic_article_13855 Research productivity has been linked to a country’s intellectual and economic wealth. Further analysis is needed to assess the association between the distribution of research across disciplines and the economic status of countries.MethodsBy using 55 years of data, spanning 1962 to 2017, of Elsevier publications across a large set of research disciplines and countries globally, this manuscript explores the relationship and evolution of relative research productivity across different disciplines through a network analysis. It also explores the associations of those with economic productivity categories, as measured by the World Bank economic classification. Additional analysis of discipline similarities is possible by exploring the cross-country evolution of those disciplines.ResultsResults show similarities in the relative importance of research disciplines among most high-income countries, with larger idiosyncrasies appearing among the remaining countries. This group of high-income countries shows similarities in the dynamics of the relative distribution of research productivity over time, forming a stable research productivity cluster. Lower income countries form smaller, more independent and evolving clusters, and differ significantly from each other and from higher income countries in the relative importance of their research emphases. Country-based similarities in research productivity profiles also appear to be influenced by geographical proximity.ConclusionsThis new form of analyses of research productivity, and its relation to economic status, reveals novel insights to the dynamics of the economic and research structure of countries. This allows for a deeper understanding of the role a country’s research structure may play in shaping its economy, and also identification of benchmark resource allocations across disciplines for developing countries. ]]> <![CDATA[Left powerless: A qualitative social media content analysis of the Dutch #breakthesilence campaign on negative and traumatic experiences of labour and birth]]> https://www.researchpad.co/article/elastic_article_13813 Disrespect and abuse during labour and birth are increasingly reported all over the world. In 2016, a Dutch client organization initiated an online campaign, #genoeggezwegen (#breakthesilence) which encouraged women to share negative and traumatic maternity care experiences. This study aimed (1) to determine what types of disrespect and abuse were described in #genoeggezwegen and (2) to gain a more detailed understanding of these experiences.MethodsA qualitative social media content analysis was carried out in two phases. (1) A deductive coding procedure was carried out to identify types of disrespect and abuse, using Bohren et al.’s existing typology of mistreatment during childbirth. (2) A separate, inductive coding procedure was performed to gain further understanding of the data.Results438 #genoeggezwegen stories were included. Based on the typology of mistreatment during childbirth, it was found that situations of ineffective communication, loss of autonomy and lack of informed consent and confidentiality were most often described. The inductive analysis revealed five major themes: ‘‘lack of informed consent”; ‘‘not being taken seriously and not being listened to”; ‘‘lack of compassion”; ‘‘use of force”; and ‘‘short and long term consequences”. “Left powerless” was identified as an overarching theme that occurred throughout all five main themes.ConclusionThis study gives insight into the negative and traumatic maternity care experiences of Dutch women participating in the #genoeggezwegen campaign. This may indicate that disrespect and abuse during labour and birth do happen in the Netherlands, although the current study gives no insight into prevalence. The findings of this study may increase awareness amongst maternity care providers and the community of the existence of disrespect and abuse in Dutch maternity care, and encourage joint effort on improving care both individually and systemically/institutionally. ]]> <![CDATA[Medusa: Software to build and analyze ensembles of genome-scale metabolic network reconstructions]]> https://www.researchpad.co/article/elastic_article_7734 Uncertainty in the structure and parameters of networks is ubiquitous across computational biology. In constraint-based reconstruction and analysis of metabolic networks, this uncertainty is present both during the reconstruction of networks and in simulations performed with them. Here, we present Medusa, a Python package for the generation and analysis of ensembles of genome-scale metabolic network reconstructions. Medusa builds on the COBRApy package for constraint-based reconstruction and analysis by compressing a set of models into a compact ensemble object, providing functions for the generation of ensembles using experimental data, and extending constraint-based analyses to ensemble scale. We demonstrate how Medusa can be used to generate ensembles and perform ensemble simulations, and how machine learning can be used in conjunction with Medusa to guide the curation of genome-scale metabolic network reconstructions. Medusa is available under the permissive MIT license from the Python Packaging Index (https://pypi.org) and from github (https://github.com/opencobra/Medusa), and comprehensive documentation is available at https://medusa.readthedocs.io/en/latest.

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<![CDATA[Mechanism to prevent the abuse of IPv6 fragmentation in OpenFlow networks]]> https://www.researchpad.co/article/elastic_article_7717 OpenFlow makes a network highly flexible and fast-evolving by separating control and data planes. The control plane thus becomes responsive to changes in topology and load balancing requirements. OpenFlow also offers a new approach to handle security threats accurately and responsively. Therefore, it is used as an innovative firewall that acts as a first-hop security to protect networks against malicious users. However, the firewall provided by OpenFlow suffers from Internet protocol version 6 (IPv6) fragmentation, which can be used to bypass the OpenFlow firewall. The OpenFlow firewall cannot identify the message payload unless the switch implements IPv6 fragment reassembly. This study tests the IPv6 fragmented packets that can evade the OpenFlow firewall, and proposes a new mechanism to guard against attacks carried out by malicious users to exploit IPv6 fragmentation loophole in OpenFlow networks. The proposed mechanism is evaluated in a simulated environment by using six scenarios, and results exhibit that the proposed mechanism effectively fixes the loophole and successfully prevents the abuse of IPv6 fragmentation in OpenFlow networks.

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<![CDATA["Clicks, likes, shares and comments" a systematic review of breast cancer screening discourse in social media]]> https://www.researchpad.co/article/N8d8d3073-6769-4a60-aed8-e2beb958c228

Background

Unsatisfactory participation rate at population based organised breast cancer screening is a long standing problem. Social media, with 3.2 billion users in 2019, is potentially an important site of breast cancer related discourse. Determining whether these platforms might be used as channels by screening providers to reach under-screened women may have considerable public health significance.

Objectives

By systematically reviewing original research studies on breast cancer related social media discourse, we had two aims: first, to assess the volume, participants and content of breast screening social media communication and second, to find out whether social media can be used by screening organisers as a channel of patient education.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After searching PubMed, ScienceDirect, Web of Science, Springer and Ebsco, 17 studies were found that met our criteria. A systematic narrative framework was used for data synthesis. Owing to the high degree of heterogeneity in social media channels, outcomes and measurement included in this study, a meta-analytic approach was not appropriate.

Results

The volume of breast cancer related social media discourse is considerable. The majority of participants are lay individuals as opposed to healthcare professionals or advocacy groups. The lay misunderstandings surrounding the harms and benefits of mammography is well mirrored in the content of social media discourse. Although there is criticism, breast cancer screening sentiment on the social media ranges from the neutral to the positive. Social media is suitable for offering peer emotional support for potential participants.

Conclusion

Dedicated breast screening websites operated by screening organisers would ensure much needed quality controlled information and also provide space for reliable question and answer forums, the sharing of personal experience and the provision of peer and professional support.

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<![CDATA[Mapping the coevolution, leadership and financing of research on viral vectors, RNAi, CRISPR/Cas9 and other genomic editing technologies]]> https://www.researchpad.co/article/N5b989351-f842-4a35-9237-928ff4c9c806

Genomic editing technologies are developing rapidly, promising significant developments for biomedicine, agriculture and other fields. In the present investigation, we analyzed and compared the process of innovation for six genomic technologies: viral vectors, RNAi, TALENs, meganucleases, ZFNs and CRISPR/Cas including the profile of the main research institutions and their funders, to understand how innovation evolved and what institutions influenced research trajectories. A Web of Science search of papers on viral vectors RNAi, CRISPR/Cas, TALENs, ZFNs and meganucleases was used to build a citation network of 16,746 papers. An analysis of network clustering combined with text mining was performed. For viral vectors, a long-term process of incremental innovation was identified, which was largely publicly funded in the United States and the European Union. The trajectory of RNAi research included clusters related to the study of RNAi as a biological phenomenon and its use in functional genomics, biomedicine and pest control. A British philanthropic organization and a US pharmaceutical company played a key role in the development of basic RNAi research and clinical application respectively, in addition to government and academic institutions. In the case of CRISPR/Cas research, basic science discoveries led to the technical improvements, and these two in turn provided the information required for the development of biomedical, agricultural, livestock and industrial applications. The trajectory of CRISPR/Cas research exhibits a geopolitical division of the investigation efforts between the US, as the main producer and funder of basic research and technical improvements, and Chinese research institutions increasingly leading applied research. Our results reflect a change in the model for financing science, with reduced public financing for basic science and applied research on publicly funded technological developments in the US, and the emergence of China as a scientific superpower, with implications for the development of applications of genomic technologies.

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<![CDATA[Mental health problems and social media exposure during COVID-19 outbreak]]> https://www.researchpad.co/article/Nb7fad802-34c4-4007-a6dc-8e780c86cbf8

Huge citizens expose to social media during a novel coronavirus disease (COVID-19) outbroke in Wuhan, China. We assess the prevalence of mental health problems and examine their association with social media exposure. A cross-sectional study among Chinese citizens aged≥18 years old was conducted during Jan 31 to Feb 2, 2020. Online survey was used to do rapid assessment. Total of 4872 participants from 31 provinces and autonomous regions were involved in the current study. Besides demographics and social media exposure (SME), depression was assessed by The Chinese version of WHO-Five Well-Being Index (WHO-5) and anxiety was assessed by Chinese version of generalized anxiety disorder scale (GAD-7). multivariable logistic regressions were used to identify associations between social media exposure with mental health problems after controlling for covariates. The prevalence of depression, anxiety and combination of depression and anxiety (CDA) was 48.3% (95%CI: 46.9%-49.7%), 22.6% (95%CI: 21.4%-23.8%) and 19.4% (95%CI: 18.3%-20.6%) during COVID-19 outbroke in Wuhan, China. More than 80% (95%CI:80.9%-83.1%) of participants reported frequently exposed to social media. After controlling for covariates, frequently SME was positively associated with high odds of anxiety (OR = 1.72, 95%CI: 1.31–2.26) and CDA (OR = 1.91, 95%CI: 1.52–2.41) compared with less SME. Our findings show there are high prevalence of mental health problems, which positively associated with frequently SME during the COVID-19 outbreak. These findings implicated the government need pay more attention to mental health problems, especially depression and anxiety among general population and combating with “infodemic” while combating during public health emergency.

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<![CDATA[Would you like to participate in this trial? The practice of informed consent in intrapartum research in the last 30 years]]> https://www.researchpad.co/article/Na45ec8a9-d35b-4ecd-a654-0f10371697fd

Background

Informed consent is the cornerstone of the ethical conduct and protection of the rights and wellbeing of participants in clinical research. Therefore, it is important to identify the most appropriate moments for the participants to be informed and to give consent, so that they are able to make a responsible and autonomous decision. However, the optimal timing of consent in clinical research during the intrapartum period remains controversial, and currently, there is no clear guidance.

Objective

We aimed to describe practices of informed consent in intrapartum care clinical research in the last three decades, as reported in uterotonics for postpartum haemorrhage prevention trials.

Methods

This is a secondary analysis of the studies included in the Cochrane review entitled “Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis” published in 2018. All the reports included in the Cochrane network meta-analysis were eligible for inclusion in this analysis, except for those reported in languages other than English, French or Spanish. We extracted and synthesized data on the time each of the components of the informed consent process occurred.

Results

We assessed data from 192 studies, out of 196 studies included in the Cochrane review. The majority of studies (59.9%, 115 studies) reported that women were informed about the study, without specifying the timing. When reported, most studies informed women at admission to the facility for childbirth. Most of the studies reported that consent was sought, but only 59.9% reported the timing, which in most of the cases, was at admission for childbirth. Among these, 32 studies obtained consent in the active phase of labour, 17 in the latent phase and in 10 studies the labour status was unknown. Women were consented antenatally in 6 studies and in 8 studies the consent was obtained indistinctly during antenatal care or at admission. Most of the studies did not specified who was the person who sought the informed consent.

Conclusion

Practices of informed consent in trials on use of uterotonics for prevention of postpartum haemorrhage showed variability and substandard reporting. Informed consent sought at admission for childbirth was the most frequent approach implemented in these trials.

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<![CDATA[Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2]]> https://www.researchpad.co/article/N35618ab8-cca5-47c4-ba7f-8d3941adbaaf

Background

The molecular changes involved in Alzheimer’s disease (AD) progression remain unclear since we cannot easily access antemortem human brains. Some non-mammalian vertebrates such as the zebrafish preserve AD-relevant transcript isoforms of the PRESENILIN genes lost from mice and rats. One example is PS2V, the alternative transcript isoform of the PSEN2 gene. PS2V is induced by hypoxia/oxidative stress and shows increased expression in late onset, sporadic AD brains. A unique, early onset familial AD mutation of PSEN2, K115fs, mimics the PS2V coding sequence suggesting that forced, early expression of PS2V-like isoforms may contribute to AD pathogenesis. Here we use zebrafish to model the K115fs mutation to investigate the effects of forced PS2V-like expression on the transcriptomes of young adult and aged adult brains.

Methods

We edited the zebrafish genome to model the K115fs mutation. To explore its effects at the molecular level, we analysed the brain transcriptome and proteome of young (6-month-old) and aged (24-month-old) wild type and heterozygous mutant female sibling zebrafish. Finally, we used gene co-expression network analysis (WGCNA) to compare molecular changes in the brains of these fish to human AD.

Results

Young heterozygous mutant fish show transcriptional changes suggesting accelerated brain aging and increased glucocorticoid signalling. These early changes precede a transcriptional ‘inversion’ that leads to glucocorticoid resistance and other likely pathological changes in aged heterozygous mutant fish. Notably, microglia-associated immune responses regulated by the ETS transcription factor family are altered in both our zebrafish mutant model and in human AD. The molecular changes we observe in aged heterozygous mutant fish occur without obvious histopathology and possibly in the absence of Aβ.

Conclusions

Our results suggest that forced expression of a PS2V-like isoform contributes to immune and stress responses favouring AD pathogenesis. This highlights the value of our zebrafish genetic model for exploring molecular mechanisms involved in AD pathogenesis.

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<![CDATA[Exponential random graph model parameter estimation for very large directed networks]]> https://www.researchpad.co/article/N437fb42a-ebf8-44aa-9399-d12b1354408e

Exponential random graph models (ERGMs) are widely used for modeling social networks observed at one point in time. However the computational difficulty of ERGM parameter estimation has limited the practical application of this class of models to relatively small networks, up to a few thousand nodes at most, with usually only a few hundred nodes or fewer. In the case of undirected networks, snowball sampling can be used to find ERGM parameter estimates of larger networks via network samples, and recently published improvements in ERGM network distribution sampling and ERGM estimation algorithms have allowed ERGM parameter estimates of undirected networks with over one hundred thousand nodes to be made. However the implementations of these algorithms to date have been limited in their scalability, and also restricted to undirected networks. Here we describe an implementation of the recently published Equilibrium Expectation (EE) algorithm for ERGM parameter estimation of large directed networks. We test it on some simulated networks, and demonstrate its application to an online social network with over 1.6 million nodes.

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<![CDATA[Incidence of statin use in older adults with and without cardiovascular disease and diabetes mellitus, January 2008- March 2018]]> https://www.researchpad.co/article/N40ec07ea-30b4-4753-a09f-b8fe9ef6ec46

Background

Data from randomized controlled trials and observational studies on older adults who take statins for primary prevention of atherosclerotic cardiovascular disease are limited. To determine the incidence of statin use in older adults with and without cardiovascular disease (CVD) and/or diabetes (DM), we conducted a descriptive observational study.

Methods

The cohort consisted of health plan members in the NIH Collaboratory Distributed Research Network aged >75 years who had continuous drug and medical benefits for ≥183 days during the study period, January 1, 2008- March 31, 2018. We defined DM and CVD using diagnosis codes, and identified statins using dispensing data. Statin use was considered incident if a member had no evidence of statin exposure in the claims during the previous 183 days, and the use was considered long-term if statins were supplied for ≥180 days. Incidence rates were reported among members with and without CVD and/or diabetes, and stratified by year, sex, and age group.

Results

Among 757,569 eligible members, 109,306 older adults initiated statins and 54,624 became long-term users. Health plan members with CVD had the highest incidence of statin use (143.9 initiators per 1,000 member-years for CVD & DM; 114.5 initiators per 1,000 member-years for CVD & No DM). Among health plan members without CVD, those with DM had rates of statin use that were over two times higher than members without DM (76.1 versus 34.5 initiators per 1,000 member-years, respectively). Statin initiation remained steady throughout 2008–2016, was slightly higher in males, and declined with increasing age.

Conclusion

Incidence of statin use varied by CVD and DM comorbidity, and was lowest among those without CVD. These results highlight the potential clinical equipoise to conduct large pragmatic clinical trials to generate evidence that could be used to inform future blood cholesterol guidelines.

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<![CDATA[Algorithmic bias amplifies opinion fragmentation and polarization: A bounded confidence model]]> https://www.researchpad.co/article/5c8823d7d5eed0c484639133

The flow of information reaching us via the online media platforms is optimized not by the information content or relevance but by popularity and proximity to the target. This is typically performed in order to maximise platform usage. As a side effect, this introduces an algorithmic bias that is believed to enhance fragmentation and polarization of the societal debate. To study this phenomenon, we modify the well-known continuous opinion dynamics model of bounded confidence in order to account for the algorithmic bias and investigate its consequences. In the simplest version of the original model the pairs of discussion participants are chosen at random and their opinions get closer to each other if they are within a fixed tolerance level. We modify the selection rule of the discussion partners: there is an enhanced probability to choose individuals whose opinions are already close to each other, thus mimicking the behavior of online media which suggest interaction with similar peers. As a result we observe: a) an increased tendency towards opinion fragmentation, which emerges also in conditions where the original model would predict consensus, b) increased polarisation of opinions and c) a dramatic slowing down of the speed at which the convergence at the asymptotic state is reached, which makes the system highly unstable. Fragmentation and polarization are augmented by a fragmented initial population.

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<![CDATA[Individual-based network model for Rift Valley fever in Kabale District, Uganda]]> https://www.researchpad.co/article/5c8823c9d5eed0c484638ffb

Rift Valley fever (RVF) is a zoonotic disease, that causes significant morbidity and mortality among ungulate livestock and humans in endemic regions. In East Africa, the causative agent of the disease is Rift Valley fever virus (RVFV) which is primarily transmitted by multiple mosquito species in Aedes and Mansonia genera during both epizootic and enzootic periods in a complex transmission cycle largely driven by environmental and climatic factors. However, recent RVFV activity in Uganda demonstrated the capability of the virus to spread into new regions through livestock movements, and underscored the need to develop effective mitigation strategies to reduce transmission and prevent spread among cattle populations. We simulated RVFV transmission among cows in 22 different locations of the Kabale District in Uganda using real world livestock data in a network-based model. This model considered livestock as a spatially explicit factor in different locations subjected to specific vector and environmental factors, and was configured to investigate and quantitatively evaluate the relative impacts of mosquito control, livestock movement, and diversity in cattle populations on the spread of the RVF epizootic. We concluded that cattle movement should be restricted for periods of high mosquito abundance to control epizootic spreading among locations during an RVF outbreak. Importantly, simulation results also showed that cattle populations with heterogeneous genetic diversity as crossbreeds were less susceptible to infection compared to homogenous cattle populations.

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<![CDATA[Exploit fully automatic low-level segmented PET data for training high-level deep learning algorithms for the corresponding CT data]]> https://www.researchpad.co/article/5c8823d0d5eed0c484639091

We present an approach for fully automatic urinary bladder segmentation in CT images with artificial neural networks in this study. Automatic medical image analysis has become an invaluable tool in the different treatment stages of diseases. Especially medical image segmentation plays a vital role, since segmentation is often the initial step in an image analysis pipeline. Since deep neural networks have made a large impact on the field of image processing in the past years, we use two different deep learning architectures to segment the urinary bladder. Both of these architectures are based on pre-trained classification networks that are adapted to perform semantic segmentation. Since deep neural networks require a large amount of training data, specifically images and corresponding ground truth labels, we furthermore propose a method to generate such a suitable training data set from Positron Emission Tomography/Computed Tomography image data. This is done by applying thresholding to the Positron Emission Tomography data for obtaining a ground truth and by utilizing data augmentation to enlarge the dataset. In this study, we discuss the influence of data augmentation on the segmentation results, and compare and evaluate the proposed architectures in terms of qualitative and quantitative segmentation performance. The results presented in this study allow concluding that deep neural networks can be considered a promising approach to segment the urinary bladder in CT images.

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<![CDATA[Electrical synapses regulate both subthreshold integration and population activity of principal cells in response to transient inputs within canonical feedforward circuits]]> https://www.researchpad.co/article/5c7d95e0d5eed0c484734e89

As information about the world traverses the brain, the signals exchanged between neurons are passed and modulated by synapses, or specialized contacts between neurons. While neurotransmitter-based synapses tend to exert either excitatory or inhibitory pulses of influence on the postsynaptic neuron, electrical synapses, composed of plaques of gap junction channels, continuously transmit signals that can either excite or inhibit a coupled neighbor. A growing body of evidence indicates that electrical synapses, similar to their chemical counterparts, are modified in strength during physiological neuronal activity. The synchronizing role of electrical synapses in neuronal oscillations has been well established, but their impact on transient signal processing in the brain is much less understood. Here we constructed computational models based on the canonical feedforward neuronal circuit and included electrical synapses between inhibitory interneurons. We provided discrete closely-timed inputs to the circuits, and characterize the influence of electrical synapse strength on both subthreshold summation and spike trains in the output neuron. Our simulations highlight the diverse and powerful roles that electrical synapses play even in simple circuits. Because these canonical circuits are represented widely throughout the brain, we expect that these are general principles for the influence of electrical synapses on transient signal processing across the brain.

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<![CDATA[Latent influence networks in global environmental politics]]> https://www.researchpad.co/article/5c8acc3cd5eed0c48498f26a

International environmental treaties are the key means by which states overcome collective action problems and make specific commitments to address environmental issues. However, systematically assessing states’ influence in promoting global environmental protection has proven difficult. Analyzing newly compiled data with a purpose-built statistical model, we provide a novel measurement of state influence within the scope of environmental politics and find strong influences among states and treaties. Specifically, we report evidence that states are less likely to ratify when states within their region ratify, and results suggesting that countries positively influence other countries at similar levels of economic development. By examining several prominent treaties, we illustrate the complex nature of influence: a single act of ratification can dramatically reshape global environmental politics. More generally, our findings and approach provide an innovative means to understand the evolution and complexity of international environmental protection.

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<![CDATA[Matching response to need: What makes social networks fit for providing bereavement support?]]> https://www.researchpad.co/article/5c8accc6d5eed0c48498ff77

The objectives of this study were to explore the goodness of fit between the bereaved peoples’ needs and the support offered by their social networks; to ascertain whether this support was experienced as helpful or unhelpful by bereaved people; and to explore both the types of social networks that offer effective support and the characteristics of the communities that encourage and nurture such networks. This study was based on qualitative interviews from twenty bereaved people, in Western Australia, interviewed in 2013. A framework analysis of these interviews was undertaken using a deductive approach based on the goodness of fit framework. Much of this support is provided informally in community settings by a range of people already involved in the everyday lives of those recently bereaved; and that support can be helpful or unhelpful depending on its amount, timing, function and structure. Improving the fit between the bereaved person’s needs and the support offered may thus involve identifying and enhancing the caring capacity of existing networks. An important strategy for achieving this is to train community members in mapping and developing these naturally occurring networks. Some such networks will include relationships of long standing, others may be circles of care formed during a period of caring. Peer support bereavement networks develop from these existing networks and may also recruit new members who were not part of the caring circle. The findings endorse social models of bereavement care that fit within a public health approach rather than relying solely on professional care. As exemplified by Compassionate Communities policies and practices, establishing collaboration between community networks and professional services is vital for effective and sustainable bereavement care.

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<![CDATA[Indirect treatment comparisons including network meta-analysis: Lenvatinib plus everolimus for the second-line treatment of advanced/metastatic renal cell carcinoma]]> https://www.researchpad.co/article/5c8823dbd5eed0c484639163

Background

In the absence of clinical trials providing direct efficacy results, this study compares different methods of indirect treatment comparison (ITC), and their respective impacts on efficacy estimates for lenvatinib (LEN) plus everolimus (EVE) combination therapy compared to other second-line treatments for advanced/metastatic renal cell carcinoma (a/mRCC).

Methods

Using EVE alone as the common comparator, the Bucher method for ITC compared LEN + EVE with cabozantinib (CAB), nivolumab (NIV), placebo (PBO) and axitinib (AXI). Hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) estimated the impact of applying three versions of the LEN+EVE trial data in separate ITCs. Last, to overcome exchangeability bias and potential violations to the proportional hazards assumption, a network meta-analysis using fractional polynomials was performed.

Results

Bucher ITCs demonstrated LEN + EVE superiority over EVE for PFS, indirect superiority to NIV, AXI, and PBO, and no difference to CAB. For OS, LEN + EVE was superior to EVE and indirectly superior to PBO, applying original HOPE 205 data. Using European Medicines Agency data, LEN + EVE was directly superior to EVE for OS. Fractional polynomial HRs for PFS and OS substantially overlapped with Bucher estimates, demonstrating LEN+EVE superiority over EVE, alone, NIV, and CAB. However, there were no statistically significant results as the credible intervals for HR crossed 1.0.

Conclusions

Comparing three Bucher ITCs, LEN + EVE demonstrated superior PFS when indirectly compared to NIV, AXI, and PBO, and mixed results for OS. While fractional polynomial modelling for PFS and OS failed to find statistically significant differences in LEN + EVE efficacy, the overall HR trends were comparable.

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<![CDATA[An efficient resource utilization scheme within PMIPv6 protocol for urban vehicular networks]]> https://www.researchpad.co/article/5c8acc80d5eed0c48498f8b1

Recently, the mobility management of urban vehicular networks has become great challenges for researchers due to its unique mobility requirements imposed by mobile users when accessing different services in a random fashion. To provide a ubiquitous Internet and seamless connectivity, the Internet Engineering Task Force (IETF) has proposed a Proxy Mobile IPv6 (PMIPv6) protocol. This is meant to address the signaling of the mobility transparent to the Mobile Node (MN) and also guarantee session continuity while the MN is in motion. However, performing a handoff by tens of thousands of MNs may harm the performance of the system significantly due to the high signaling overhead and the insufficient utilization of so-called Binding Cash Entry (BCE) at the Local Mobility Anchor (LMA). To address these issues, we propose an efficient scheme within the PMIPv6 protocol, named AE-PMIPv6 scheme, to effectively utilize the BCE at the LMA. This is primarily achieved by merging the BCEs of the MNs, thus, reducing the signaling overhead. Better utilization of the BCEs has been attained by employing virtual addresses and addressing pool mechanisms for the purpose of binding information of the MNs that are moving together towards the same network at a specific time, during their handoff process. Results obtained from our simulation demonstrates the superiority of AE-PMIPv6 scheme over E-PMIPv6 scheme. The AE-PMIPv6 succeeds in minimizing the signaling overhead, reduces the handover time and at the same time efficiently utilize the buffer resources.

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<![CDATA[HCV transmission in high-risk communities in Bulgaria]]> https://www.researchpad.co/article/5c882406d5eed0c4846395b0

Background

The rate of HIV infection in Bulgaria is low. However, the rate of HCV-HIV-coinfection and HCV infection is high, especially among high-risk communities. The molecular epidemiology of those infections has not been studied before.

Methods

Consensus Sanger sequences of HVR1 and NS5B from 125 cases of HIV/HCV coinfections, collected during 2010–2014 in 15 different Bulgarian cities, were used for preliminary phylogenetic evaluation. Next-generation sequencing (NGS) data of the hypervariable region 1 (HVR1) analyzed via the Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to evaluate genetic heterogeneity and possible transmission linkages. Links between pairs that were below and above the established genetic distance threshold, indicative of transmission, were further examined by generating k-step networks.

Results

Preliminary genetic analyses showed predominance of HCV genotype 1a (54%), followed by 1b (20.8%), 2a (1.4%), 3a (22.3%) and 4a (1.4%), indicating ongoing transmission of many HCV strains of different genotypes. NGS of HVR1 from 72 cases showed significant genetic heterogeneity of intra-host HCV populations, with 5 cases being infected with 2 different genotypes or subtypes and 6 cases being infected with 2 strains of same subtype. GHOST revealed 8 transmission clusters involving 30 cases (41.7%), indicating a high rate of transmission.

Four transmission clusters were found in Sofia, three in Plovdiv, and one in Peshtera. The main risk factor for the clusters was injection drug use. Close genetic proximity among HCV strains from the 3 Sofia clusters, and between HCV strains from Peshtera and one of the two Plovdiv clusters confirms a long and extensive transmission history of these strains in Bulgaria.

Conclusions

Identification of several HCV genotypes and many HCV strains suggests a frequent introduction of HCV to the studied high-risk communities. GHOST detected a broad transmission network, which sustains circulation of several HCV strains since their early introduction in the 3 cities. This is the first report on the molecular epidemiology of HIV/HCV coinfections in Bulgaria.

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