Lymphatic Migration of Immune Cells.

Lymphatic vessels collect interstitial fluid that has extravasated from blood vessels and return it to the circulatory system. Another important function of the lymphatic network is to facilitate immune cell migration and antigen transport from the periphery to draining lymph nodes. This migration plays a crucial role in immune surveillance, initiation of immune responses and tolerance. Here we discuss the significance and mechanisms of lymphatic migration of innate and adaptive immune cells in homeostasis, inflammation and cancer

Lymphatic Migration of Immune Cells

Lymphatic vessels collect interstitial fluid that has extravasated from blood vessels and return it to the circulatory system. Another important function of the lymphatic network is to facilitate immune cell migration and antigen transport from the periphery to draining lymph nodes. This migration plays a crucial role in immune surveillance, initiation of immune responses and tolerance. Here we discuss the significance and mechanisms of lymphatic migration of innate and adaptive immune cells in homeostasis, inflammation and cancer

Closing the (service) gap: exploring partnerships between Aboriginal and mainstream health services

Background: Although effective partnerships between Aboriginal and mainstream health services are critical to improve Aboriginal health outcomes, many factors can cause these partnerships to be tenuous and unproductive. Understanding the elements of best practice for successful partnerships is essential. Methods: A literature review was conducted in 2009 using keyword searches of electronic databases. Sourced literature was assessed for relevance regarding the benefits, challenges, lessons learnt and factors contributing to successful Aboriginal and mainstream partnerships. Key themes were collated. Results: Although there is much literature regarding general partnerships generally, few specifically examine Aboriginal and mainstream health service partnerships. Twenty-four sources were reviewed in detail. Benefits include broadening service capacity and improving the cultural security of healthcare. Challenges include the legacy of Australia’s colonial history, different approaches to servicing clients and resource limitations. Recommendations for success include workshopping tensions early, building trust and leadership. Conclusion: Although successful partnerships are crucial to optimise Aboriginal health outcomes, failed collaborations risk inflaming sensitive Aboriginal–non-Aboriginal relationships. Factors supporting successful partnerships remind us to develop genuine, trusting relationships that are tangibly linked to the Aboriginal community. Failure to invest in this relational process and push forward with ‘business as usual’ can ultimately have negative ramifications on client outcomes. What is known about the topic? Partnerships between different health services have long been recognised as beneficial for broadening service capacity and using resources more effectively to improve client care. The current policy climate particularly recognises partnerships between Aboriginal and mainstream services as offering multiple benefits for improving the cultural and clinical capacity of health service delivery to Aboriginal clients. Yet many challenges face these arrangements, including tensions stemming from historical and current race relations, different ways of working and ongoing Aboriginal disadvantage. What does this paper add? Although partnerships between Aboriginal and mainstream services are strongly advocated for, there is a paucity of research on the challenges in these arrangements and practical suggestions on how to make such partnerships genuinely successful. This paper analyses the results from research, case studies, reports and reviews to identify the factors that challenge and enhance partnerships between Aboriginal and mainstream health services. The collation of this information also enables indicators of best practice to be presented. What are the implications for practitioners? Although there are considerable challenges for Aboriginal and mainstream health services entering into partnerships, this paper offers health service practitioners and managers a summary of lessons learnt and a ‘checklist’ of best practice indicators to assist them in developing, implementing and sustaining a successful collaborative arrangement

T Follicular Helper Cells Have Distinct Modes of Migration and Molecular Signatures in Naive and Memory Immune Responses

SummaryB helper follicular T (Tfh) cells are critical for long-term humoral immunity. However, it remains unclear how these cells are recruited and contribute to secondary immune responses. Here we show that primary Tfh cells segregate into follicular mantle (FM) and germinal center (GC) subpopulations that display distinct gene expression signatures. Restriction of the primary Tfh cell subpopulation in the GC was mediated by downregulation of chemotactic receptor EBI2. Following collapse of the GC, memory T cells persisted in the outer follicle where they scanned CD169+ subcapsular sinus macrophages. Reactivation and intrafollicular expansion of these follicular memory T cells in the subcapsular region was followed by their extrafollicular dissemination via the lymphatic flow. These data suggest that Tfh cells integrate their antigen-experience history to focus T cell help within the GC during primary responses but act rapidly to provide systemic T cell help after re-exposure to the antigen

Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic.

Abstract We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after≥5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL≤1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures

Legal and Ethical Implications of Mobile Live-Streaming Video Apps

The introduction of mobile apps such as Meerkat, Periscope, and Facebook Live has sparked enthusiasm for live-streaming video. This study explores the legal and ethical implications of mobile live-streaming video apps through a review of public-policy considerations and the computing literature as well as analyses of a mix of quantitative and qualitative user data. We identify lines of research inquiry for five policy challenges and two areas of the literature in which the impact of these apps is so far unaddressed. The detailed data gathered from these inquiries will significantly contribute to the design and development of tools, signals or affordances to address the concerns that our study identifies. We hope our work will help shape the fields of ubiquitous computing and collaborative and social computing, jurisprudence, public policy and applied ethics in the future

Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer.

Abstract Detection, treatment, and prediction of outcome for men with prostate cancer increasingly depend on a molecular understanding of tumor development and behavior. We characterized primary prostate cancer by monitoring expression levels of more than 8900 genes in normal and malignant tissues. Patterns of gene expression across tissues revealed a precise distinction between normal and tumor samples, and revealed a striking group of about 400 genes that were overexpressed in tumor tissues. We ranked these genes according to their differential expression in normal and cancer tissues by selecting for highly and specifically overexpressed genes in the majority of cancers with correspondingly low or absent expression in normal tissues. Several such genes were identified that act within a variety of biochemical pathways and encode secreted molecules with diagnostic potential, such as the secreted macrophage inhibitory cytokine, MIC-1. Other genes, such as fatty acid synthase, encode enzymes known as drug targets in other contexts, which suggests new therapeutic approaches

The Changing Face of Winter: Lessons and Questions From the Laurentian Great Lakes

Among its many impacts, climate warming is leading to increasing winter air temperatures, decreasing ice cover extent, and changing winter precipitation patterns over the Laurentian Great Lakes and their watershed. Understanding and predicting the consequences of these changes is impeded by a shortage of winter-period studies on most aspects of Great Lake limnology. In this review, we summarize what is known about the Great Lakes during their 3–6 months of winter and identify key open questions about the physics, chemistry, and biology of the Laurentian Great Lakes and other large, seasonally frozen lakes. Existing studies show that winter conditions have important effects on physical, biogeochemical, and biological processes, not only during winter but in subsequent seasons as well. Ice cover, the extent of which fluctuates dramatically among years and the five lakes, emerges as a key variable that controls many aspects of the functioning of the Great Lakes ecosystem. Studies on the properties and formation of Great Lakes ice, its effect on vertical and horizontal mixing, light conditions, and biota, along with winter measurements of fundamental state and rate parameters in the lakes and their watersheds are needed to close the winter knowledge gap. Overcoming the formidable logistical challenges of winter research on these large and dynamic ecosystems may require investment in new, specialized research infrastructure. Perhaps more importantly, it will demand broader recognition of the value of such work and collaboration between physicists, geochemists, and biologists working on the world\u27s seasonally freezing lakes and seas

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London