Merging DNA metabarcoding and ecological network analysis to understand and build resilient terrestrial ecosystems

Summary 1. Significant advances in both mathematical and molecular approaches in ecology offer unprecedented opportunities to describe and understand ecosystem functioning. Ecological networks describe interactions between species, the underlying structure of communities and the function and stability of ecosystems. They provide the ability to assess the robustness of complex ecological communities to species loss, as well as a novel way of guiding restoration. However, empirically quantifying the interactions between entire communities remains a significant challenge. 2. Concomitantly, advances in DNA sequencing technologies are resolving previously intractable questions in functional and taxonomic biodiversity and provide enormous potential to determine hitherto difficult to observe species interactions. Combining DNA metabarcoding approaches with ecological network analysis presents important new opportunities for understanding large-scale ecological and evolutionary processes, as well as providing powerful tools for building ecosystems that are resilient to environmental change. 3. We propose a novel ‘nested tagging’ metabarcoding approach for the rapid construction of large, phylogenetically structured species-interaction networks. Taking tree–insect–parasitoid ecological networks as an illustration, we show how measures of network robustness, constructed using DNA metabarcoding, can be used to determine the consequences of tree species loss within forests, and forest habitat loss within wider landscapes. By determining which species and habitats are important to network integrity, we propose new directions for forest management. 4. Merging metabarcoding with ecological network analysis provides a revolutionary opportunity to construct some of the largest, phylogenetically structured species-interaction networks to date, providing new ways to: (i) monitor biodiversity and ecosystem functioning; (ii) assess the robustness of interacting communities to species loss; and (iii) build ecosystems that are more resilient to environmental change

Functional Polycentrism and Urban Network Development in the Greater South East UK: Evidence from Commuting Patterns, 1981-2001

In contemporary literature on changing urban systems, it is often argued that the traditional central place conceptualisation is outdated and should be replaced by a network view that emphasises the increasing criss-crossing pattern of interdependencies between spatial units. This paper tests for urban network development by looking at commuting patterns in the Greater South East UK. The analysis is based on census commuting interaction data for three points in time during the past three decades (1981, 1991, and 2001). Although the empirical results indicate that the Greater South East UK can still not be characterized as a polycentric urban region or integrated urban network, there is some evidence for urban network development at the local, intra-urban, level as well as a decentralization of the system at the regional, inter-urban, level

Merging DNA metabarcoding and ecological network analysis to understand and build resilient terrestrial ecosystems

1. Significant advances in both mathematical and molecular approaches in ecology offer unprecedented opportunities to describe and understand ecosystem functioning. Ecological networks describe interactions between species, the underlying structure of communities and the function and stability of ecosystems. They provide the ability to assess the robustness of complex ecological communities to species loss, as well as a novel way of guiding restoration. However, empirically quantifying the interactions between entire communities remains a significant challenge. 2. Concomitantly, advances in DNA sequencing technologies are resolving previously intractable questions in functional and taxonomic biodiversity and provide enormous potential to determine hitherto difficult to observe species interactions. Combining DNA metabarcoding approaches with ecological network analysis presents important new opportunities for understanding large-scale ecological and evolutionary processes, as well as providing powerful tools for building ecosystems that are resilient to environmental change. 3. We propose a novel ‘nested tagging’ metabarcoding approach for the rapid construction of large, phylogenetically structured species-interaction networks. Taking tree–insect–parasitoid ecological networks as an illustration, we show how measures of network robustness, constructed using DNA metabarcoding, can be used to determine the consequences of tree species loss within forests, and forest habitat loss within wider landscapes. By determining which species and habitats are important to network integrity, we propose new directions for forest management. 4. Merging metabarcoding with ecological network analysis provides a revolutionary opportunity to construct some of the largest, phylogenetically structured species-interaction networks to date, providing new ways to: (i) monitor biodiversity and ecosystem functioning; (ii) assess the robustness of interacting communities to species loss; and (iii) build ecosystems that are more resilient to environmental change

S100A8 & S100A9: alarmin mediated inflammation in tendinopathy

Alarmins S100A8 and S100A9 are endogenous molecules released in response to environmental triggers and cellular damage. They are constitutively expressed in immune cells such as monocytes and neutrophils and their expression is upregulated under inflammatory conditions. The molecular mechanisms that regulate inflammatory pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. Based on our previous investigations highlighting tendinopathy as an alarmin mediated pathology we sought evidence of S100A8 & A9 expression in a human model of tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate release of inflammatory mediators and matrix synthesis in human tenocytes. Immunohistochemistry and quantitative RT-PCR showed S100A8 & A9 expression was significantly upregulated in tendinopathic tissue compared with control. Furthermore, treating primary human tenocytes with exogenous S100A8 & A9 significantly increased protein release of IL-6, IL-8, CCL2, CCL20 and CXCL10; however, no alterations in genes associated with matrix remodelling were observed at a transcript level. We propose S100A8 & A9 participate in early pathology by modulating the stromal microenvironment and influencing the inflammatory profile observed in tendinopathy. S100A8 and S100A9 may participate in a positive feedback mechanism involving enhanced leukocyte recruitment and release of pro-inflammatory cytokines from tenocytes that perpetuates the inflammatory response within the tendon in the early stages of disease

Employing external facilitation to implement cognitive behavioral therapy in VA clinics: a pilot study

<p>Abstract</p> <p>Background</p> <p>Although for more than a decade healthcare systems have attempted to provide evidence-based mental health treatments, the availability and use of psychotherapies remains low. A significant need exists to identify simple but effective implementation strategies to adopt complex practices within complex systems of care. Emerging evidence suggests that facilitation may be an effective integrative implementation strategy for adoption of complex practices. The current pilot examined the use of external facilitation for adoption of cognitive behavioral therapy (CBT) in 20 Department of Veteran Affairs (VA) clinics.</p> <p>Methods</p> <p>The 20 clinics were paired on facility characteristics, and 23 clinicians from these were trained in CBT. A clinic in each pair was randomly selected to receive external facilitation. Quantitative methods were used to examine the extent of CBT implementation in 10 clinics that received external facilitation compared with 10 clinics that did not, and to better understand the relationship between individual providers' characteristics and attitudes and their CBT use. Costs of external facilitation were assessed by tracking the time spent by the facilitator and therapists in activities related to implementing CBT. Qualitative methods were used to explore contextual and other factors thought to influence implementation.</p> <p>Results</p> <p>Examination of change scores showed that facilitated therapists averaged an increase of 19% [95% CI: (2, 36)] in self-reported CBT use from baseline, while control therapists averaged a 4% [95% CI: (-14, 21)] increase. Therapists in the facilitated condition who were not providing CBT at baseline showed the greatest increase (35%) compared to a control therapist who was not providing CBT at baseline (10%) or to therapists in either condition who were providing CBT at baseline (average 3%). Increased CBT use was unrelated to prior CBT training. Barriers to CBT implementation were therapists' lack of control over their clinic schedule and poor communication with clinical leaders.</p> <p>Conclusions</p> <p>These findings suggest that facilitation may help clinicians make complex practice changes such as implementing an evidence-based psychotherapy. Furthermore, the substantial increase in CBT usage among the facilitation group was achieved at a modest cost.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

An action research approach to facilitating the adoption of a foot health assessment tool in India

Background: India has a diabetes population that is growing and alongside this, the incidence of limb threatening foot problems is increasing. Foot health care provision does not yet meet this demand. In one locality in India, clinicians had an unstructured approach to foot health assessments resulting in poor adoption of evidence based guidelines from the West and a persistence of serious foot complications. There was the perception that existing assessment tools did not take into account the local cultural, organizational and professional needs and there was a lack of ownership of any potential solution to the problem. Therefore, the aim of this work was to facilitate the ownership and development of a foot health assessment tool for use in the Indian context. In order to achieve this an action research approach was chosen. Methods: Participants were facilitated through the action and implementation phases of the action research cycle by the researchers. The action phase included generating a list of potential items for inclusion in the tool from a review of the literature to provide an evidence based foundation for the foot health assessment tool. A modified Delphi method was used to further refine the contents of the tool. Members of the Delphi Panel (n=8) were experts in their field of medicine and experts in delivering health care within services in India. Results: The outcome of the study was the adoption of a locally developed foot health assessment tool (Salford Indian Foot Health Assessment Tool, SIFT). It contains thirteen sections, which reflect the risk factors identified for assessing foot health agreed by the participants to fit the Indian context. The SIFT is supported with evidence based guidelines from the West and a training program was delivered by the researchers in order to support its implementation into clinical practice. Conclusion: An action research approach has facilitated the development and implementation of a locally created and owned foot health assessment tool. This in turn has resulted in the integration of evidence-based guidelines from the West with consideration to local cultural, organizational and professional needs and ultimately the needs of their patients. Further work is underway evaluating the outcomes of the SIFT in practice. Keywords: Diabetes; Action research; Foot health assessment

The assessment and management of diabetes related lower limb problems in India - an action research approach to integrating best practice

Background: In this article the authors explore the current issues and barriers related to achieving successful outcomes to diabetic foot complications in India. This was achieved by engaging clinicians in taking ownership of the problems and facilitating them in the identification of solutions to action change in clinical practice. Methods: This was accomplished through facilitating participants in this study via a process of problem identification and planning, the first phases of an action research cycle approach. The methods of data collection were focus groups, observations and individual conversations. The data were analysed using a thematic framework. Findings: Based on the practitioner's experiences and opinions, key themes were identified. These themes had the potential to inform the changes needed in clinical practice, to overcome barriers and embed ownership of the solutions. Five themes were identified highlighting: concerns over a fragmented service; local recognition of need; lack of standardised care pathways; lack of structured assessment and an absence of annual foot screening. Combined, the issues identified were thought to be important in preventing timely assessment and management of foot problems. Conclusion: It was unanimously agreed that a formalised process of foot assessment should be developed and implemented as part of the subsequent phases of the action research process, which the authors intended to take forward and report in a further paper. The aim of which is to guide triage, education, care pathways, audit and evaluation of outcomes. Facilitation of the clinicians in developing a program and screening tool to implement and teach these skills to others could be an important step in reducing the number of high-risk cases that are often resulting in the amputation of limbs