Structure-based programming of lymph-node targeting in molecular vaccines

In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes1, 2. Here we translate this ‘albumin hitchhiking’ approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.David H. Koch Institute for Integrative Cancer Research at MIT (Koch Institute Support (core) Grant P30-CA14051)National Cancer Institute (U.S.)National Institutes of Health (U.S.) (grant AI091693)National Institutes of Health (U.S.) (grant AI104715)National Institutes of Health (U.S.) (AI095109)United States. Dept. of Defense (contract W911NF-13-D-0001)United States. Dept. of Defense (contract W911NF-07-D-0004)Ragon Institute of MGH, MIT, and Harvar

Improving Outcomes in Infants of HIV-Infected Women in a Developing Country Setting

Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis.Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant

A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis

Introduction: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. Methods: A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. Results: In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Conclusion: Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. Systematic review: PROSPERO registration number: CRD 4201300500

Sandy coastlines under threat of erosion

Sandy beaches occupy more than one-third of the global coastline(1) and have high socioeconomic value related to recreation, tourism and ecosystem services(2). Beaches are the interface between land and ocean, providing coastal protection from marine storms and cyclones(3). However the presence of sandy beaches cannot be taken for granted, as they are under constant change, driven by meteorological(4,5), geological(6) and anthropogenic factors(1,7). A substantial proportion of the world's sandy coastline is already eroding(1,7), a situation that could be exacerbated by climate change(8,9). Here, we show that ambient trends in shoreline dynamics, combined with coastal recession driven by sea level rise, could result in the near extinction of almost half of the world's sandy beaches by the end of the century. Moderate GHG emission mitigation could prevent 40% of shoreline retreat. Projected shoreline dynamics are dominated by sea level rise for the majority of sandy beaches, but in certain regions the erosive trend is counteracted by accretive ambient shoreline changes; for example, in the Amazon, East and Southeast Asia and the north tropical Pacific. A substantial proportion of the threatened sandy shorelines are in densely populated areas, underlining the need for the design and implementation of effective adaptive measures. Erosion is a major problem facing sandy beaches that will probably worsen with climate change and sea-level rise. Half the world's beaches, many of which are in densely populated areas, could disappear by the end of the century under current trends; mitigation could lessen retreat by 40%.info:eu-repo/semantics/publishedVersio

The ability of societies to adapt to twenty-first-century sea-level rise

Against the background of potentially substantial sea-level rise, one important question is to what extent are coastal societies able to adapt? This question is often answered in the negative by referring to sinking islands and submerged megacities. Although these risks are real, the picture is incomplete because it lacks consideration of adaptation. This Perspective explores societies' abilities to adapt to twenty-first-century sea-level rise by integrating perspectives from coastal engineering, economics, finance and social sciences, and provides a comparative analysis of a set of cases that vary in terms of technological limits, economic and financial barriers to adaptation and social conflicts

A global reference for caesarean section rates (C-Model): a multicountry cross-sectional study.

OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems

Uniendo ingeniería y ecología: la protección costera basada en ecosistemas

En un contexto de crecientes impactos y riesgos socio-económicos en las costas del planeta, la protección costera basada en ecosistemas surge como un nuevo paradigma que une los principios de protección, sostenibilidad y resiliencia, a la vez que proporciona múltiples beneficios. Este artículo ofrece una perspectiva sobre qué son y cómo se pueden utilizar las defensas naturales en el diseño, planificación y gestión de costas. La política pública muestra un creciente interés por su implementación general y el cuerpo de conocimiento y experiencia alrededor de la también denominada infraestructura ?verde? es creciente, pero aún existen importantes barreras que salvar. Una de ellas es estandarizar su diseño en términos ingenieriles, así como reconocer los aspectos que los diferencian respecto a enfoques tradicionales. La adaptación climática y la reducción de riesgos son áreas en las que su utilización puede ser más significativa, debido a la variedad de servicios que ofrecen. Tanto desde el punto de vista técnico como económico, existen argumentos sólidos para evitar la degradación de los ecosistemas, avanzando su restauración y conservación, como también desde la perspectiva de la defensa de las costas.In a context of increasing socio-economic impacts and risks in the coastal areas of the planet, coastal protection based on ecosystem features becomes a new paradigm that combines the principles of conservation, sustainability and resilience, while providing multiple benefits. This paper provides a perspective on what these are and how they can be used in the design, planning and management of the coastal zones. Policy-makers are calling for further uptake and implementation across the board and the body of knowledge and experience around the socalled ?green? infrastructure is growing, but there are still major barriers for a widespread uptake. One of them is to standardize designs in engineering terms, recognizing the different characteristics compared to traditional engineering solutions. Climate adaptation and risk reduction are areas where its use may be more significant, for the variety of services they offer. Both technically and economically, there are strong arguments to prevent degradation of ecosystems and to advance in their restoration and conservation, as well as from a coastal defense perspective

The dynamics of expanding mangroves in New Zealand

In contrast to the global trend of mangrove decline, New Zealand mangroves are rapidly expanding, facilitated by elevated sediment inputs in coastal waters as a consequence of large-scale land use changes following European settlement. New Zealand mangroves are at the southern limit of the global mangrove extent, which limits the tree height of Avicennia marina var. australasica, the only mangrove species present. Mangroves in New Zealand thrive in the sheltered environments of infilling drowned river valleys with abundant supply of fine terrigenous sediments, showing various stages of mangrove succession and expansion dynamics. Bio-physical interactions and carbon dynamics in these expanding temperate mangrove systems show similarities to, but also differ from those in tropical mangrove forests, for instance due to the limited height and complexity of the mangrove communities. Likewise, ecosystem services provided by New Zealand mangroves deviate from those offered by tropical mangroves. In particular, the association of mangrove expansion with the accumulation of (the increased supply of) fine sediments and the consequent change of estuarine ecosystems, has provoked a negative perception of mangrove expansion and subsequently led to mangrove clearance. Over recent decades, a body of knowledge has been developed regarding the planning and decision making relating to mangrove removal, yet there are still effects that are unknown, for example with respect to the post-clearance recovery of the original sandflat ecosystems. In this chapter we discuss the dynamics of New Zealand’s expanding mangroves from a range of viewpoints, with the aim of elucidating the possible contributions of expanding mangroves to coastal ecosystem services, now and in the future. This chapter also reviews current policies and practice regarding mangrove removal in New Zealand and addresses the (un)known effects of mangrove clearance. These combined insights may contribute to the development of integrated coastal management strategies that recognise the full potential of expanding mangrove ecosystems

Salt Marsh Accretion and Storm Tide Variation: an Example from a Barrier Island in the North Sea

We reconstruct past accretion rates of a salt marsh on the island of Sylt, Germany, using measurements of the radioisotopes 210Pb and 137Cs, as well as historical aerial photographs. Results from three cores indicate accretion rates varying between 1 and 16 mm year−1. Comparisons with tide gauge data show that high accretion rates during the 1980s and 1990s coincide with periods of increased storm activity. We identify a critical inundation height of 18 cm below which the strength of a storm seems to positively influence salt marsh accretion rates and above which the frequency of storms becomes the major factor. In addition to sea level rise, we conclude that in low marsh zones subject to higher inundation levels, mean storm strength is the major factor affecting marsh accretion, whereas in high marsh zones with lower inundation levels, it is storm frequency that impacts marsh accretion