Immune mechanisms of protection: can adjuvants rise to the challenge?

For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens

Ecosystem development after mangrove wetland creation : plant–soil change across a 20-year chronosequence

This paper is not subject to U.S. copyright. The definitive version was published in Ecosystems 15 (2012): 848-866, doi:10.1007/s10021-012-9551-1.Mangrove wetland restoration and creation efforts are increasingly proposed as mechanisms to compensate for mangrove wetland losses. However, ecosystem development and functional equivalence in restored and created mangrove wetlands are poorly understood. We compared a 20-year chronosequence of created tidal wetland sites in Tampa Bay, Florida (USA) to natural reference mangrove wetlands. Across the chronosequence, our sites represent the succession from salt marsh to mangrove forest communities. Our results identify important soil and plant structural differences between the created and natural reference wetland sites; however, they also depict a positive developmental trajectory for the created wetland sites that reflects tightly coupled plant-soil development. Because upland soils and/or dredge spoils were used to create the new mangrove habitats, the soils at younger created sites and at lower depths (10–30 cm) had higher bulk densities, higher sand content, lower soil organic matter (SOM), lower total carbon (TC), and lower total nitrogen (TN) than did natural reference wetland soils. However, in the upper soil layer (0–10 cm), SOM, TC, and TN increased with created wetland site age simultaneously with mangrove forest growth. The rate of created wetland soil C accumulation was comparable to literature values for natural mangrove wetlands. Notably, the time to equivalence for the upper soil layer of created mangrove wetlands appears to be faster than for many other wetland ecosystem types. Collectively, our findings characterize the rate and trajectory of above- and below-ground changes associated with ecosystem development in created mangrove wetlands; this is valuable information for environmental managers planning to sustain existing mangrove wetlands or mitigate for mangrove wetland losses

Isotopic and molecular distributions of biochemicals from fresh and buried Rhizophora mangle leaves†

Rhizophora mangle L. (red mangrove) is the dominant species of mangrove in the Americas. At Twin Cays, Belize (BZ) red mangroves are present in a variety of stand structures (tall >5 m in height, transition ~2–4 m and dwarf ~1–1.5 m). These height differences are coupled with very different stable carbon and nitrogen isotopic values[1] (mean tall δ(13)C = -28.3‰, δ(15)N = 0‰; mean tall δ(13)C = -25.3‰, δ(15)N = -10‰). To determine the utility of using these distinct isotopic compositions as 'biomarkers' for paleoenvironmental reconstruction of mangrove ecosystems and nutrient availability, we investigated the distribution and isotopic (δ(13)C and δ(15)N) composition of different biochemical fractions (water soluble compounds, free lipids, acid hydrolysable compounds, individual amino acids, and the residual un-extractable compounds) in fresh and preserved red mangrove leaves from dwarf and tall trees. The distribution of biochemicals are similar in dwarf and tall red mangrove leaves, suggesting that, regardless of stand structure, red mangroves use nutrients for biosynthesis and metabolism in a similar manner. However, the δ(13)C and δ(15)N of the bulk leaf, the biochemical fractions, and seven amino acids can be used to distinguish dwarf and tall trees at Twin Cays, BZ. The data support the theory that the fractionation of carbon and nitrogen occurs prior to or during uptake in dwarf and tall red mangrove trees. Stable carbon and nitrogen isotopes could, therefore, be powerful tools for predicting levels of nutrient limitation at Twin Cays. The δ(13)C and δ(15)N of biochemical fractions within preserved leaves, reflect sedimentary cycling and nitrogen immobilization. The δ(15)N of the immobilized fraction reveals the overlying stand structure at the time of leaf deposition. The isotopic composition of preserved mangrove leaves could yield significant information about changes in ecosystem dynamics, nutrient limitation and past stand structure in mangrove paleoecosystems

Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. / Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. / Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from 66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. / Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds

Ecosystem Resilience and Threshold Response in the Galápagos Coastal Zone

Background: The Intergovernmental Panel on Climate Change (IPCC) provides a conservative estimate on rates of sea-level rise of 3.8 mm yr⁻¹ at the end of the 21st century, which may have a detrimental effect on ecologically important mangrove ecosystems. Understanding factors influencing the long-term resilience of these communities is critical but poorly understood. We investigate ecological resilience in a coastal mangrove community from the Galápagos Islands over the last 2700 years using three research questions: What are the 'fast and slow' processes operating in the coastal zone? Is there evidence for a threshold response? How can the past inform us about the resilience of the modern system?Methodology/Principal Findings: Palaeoecological methods (AMS radiocarbon dating, stable carbon isotopes (δ13C)) were used to reconstruct sedimentation rates and ecological change over the past 2,700 years at Diablas lagoon, Isabela, Galápagos. Bulk geochemical analysis was also used to determine local environmental changes, and salinity was reconstructed using a diatom transfer function. Changes in relative sea level (RSL) were estimated using a glacio-isostatic adjustment model. Non-linear behaviour was observed in the Diablas mangrove ecosystem as it responded to increased salinities following exposure to tidal inundations. A negative feedback was observed which enabled the mangrove canopy to accrete vertically, but disturbances may have opened up the canopy and contributed to an erosion of resilience over time. A combination of drier climatic conditions and a slight fall in RSL then resulted in a threshold response, from a mangrove community to a microbial mat.Conclusions/Significance: Palaeoecological records can provide important information on the nature of non-linear behaviour by identifying thresholds within ecological systems, and in outlining responses to 'fast and slow' environmental change between alternative stable states. This study highlights the need to incorporate a long-term ecological perspective when designing strategies for maximizing coastal resilience.</p

Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1

Peer reviewedPublisher PD

Long-term psychosocial functioning after Ilizarov limb lengthening during childhood: 37 patients followed for 2–14 years

Background and purpose Few studies have been concerned with the patient's perception of the outcome of limb lengthening. We describe the psychological and social functioning after at least 2 years of follow-up in patients who had had a leg length discrepancy and who had undergone an Ilizarov limb lengthening procedure

No evidence for an association between the -36A>C phospholamban gene polymorphism and a worse prognosis in heart failure

Background: In Brazil, heart failure leads to approximately 25,000 deaths per year. Abnormal calcium handling is a hallmark of heart failure and changes in genes encoding for proteins involved in the re-uptake of calcium might harbor mutations leading to inherited cardiomyopathies. Phospholamban (PLN) plays a prime role in cardiac contractility and relaxation and mutations in the gene encoding PLN have been associated with dilated cardiomyopathy. In this study, our objective was to determine the presence of the -36A>C alteration in PLN gene in a Brazilian population of individuals with HF and to test whether this alteration is associated with heart failure or with a worse prognosis of patients with HF. Methods: We genotyped a cohort of 881 patients with HF and 1259 individuals from a cohort of individuals from the general population for the alteration -36A>C in the PLN gene. Allele and genotype frequencies were compared between groups (patients and control). In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotypic groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the -36A>C were compared regarding mortality incidence in HF patients. Results: No significant association was found between the study polymorphism and HF in our population. In addition, no association between PLN -36A>C polymorphism and demographic, clinical and functional characteristics and mortality incidence in this sample of HF patients was observed. Conclusion: Our data do not support a role for the PLN -36A>C alteration in modulating the heart failure phenotype, including its clinical course, in humans

A framework for developing an evidence-based, comprehensive tobacco control program

BACKGROUND: Tobacco control is an area where the translation of evidence into policy would seem to be straightforward, given the wealth of epidemiological, behavioural and other types of research available. Yet, even here challenges exist. These include information overload, concealment of key (industry-funded) evidence, contextualization, assessment of population impact, and the changing nature of the threat. METHODS: In the context of Israel's health targeting initiative, Healthy Israel 2020, we describe the steps taken to develop a comprehensive tobacco control strategy. We elaborate on the following: a) scientific issues influencing the choice of tobacco control strategies; b) organization of existing evidence of effectiveness of interventions into a manageable form, and c) consideration of relevant philosophical and political issues. We propose a framework for developing a plan and illustrate this process with a case study in Israel. RESULTS: Broad consensus exists regarding the effectiveness of most interventions, but current recommendations differ in the emphasis they place on different strategies. Scientific challenges include integration of complex and sometimes conflicting information from authoritative sources, and lack of estimates of population impact of interventions. Philosophical and political challenges include the use of evidence-based versus innovative policymaking, the importance of individual versus governmental responsibility, and whether and how interventions should be prioritized.The proposed framework includes: 1) compilation of a list of potential interventions 2) modification of that list based on local needs and political constraints; 3) streamlining the list by categorizing interventions into broad groupings of related interventions; together these groupings form the basis of a comprehensive plan; and 4) refinement of the plan by comparing it to existing comprehensive plans. CONCLUSIONS: Development of a comprehensive tobacco control plan is a complex endeavour, involving crucial decisions regarding intervention components. "Off the shelf" plans, which need to be adapted to local settings, are available from a variety of sources, and a multitude of individual recommendations are available. The proposed framework for adapting existing approaches to the local social and political climate may assist others planning for smoke-free societies. Additionally, this experience has implications for development of evidence-based health plans addressing other risk factors

Hepatitis C infection: eligibility for antiviral therapies

peer reviewedBackground Current treatments of chronic hepatitis C virus (HCV) are effective, but expensive and susceptible to induce significant side effects. Objectives To evaluate the proportion of HCV patients who are eligible for a treatment. Methods In a database comprising 1726 viraemic HCV patients, the files of 299 patients who presented to the same hepatologist for an initial appointment between 1996 and 2003 were reviewed. Results Patients' characteristics were age 43.1 +/- 15.6 years, 53% male and 92% Caucasian. The main risk factors were transfusion (43%) and drug use (22%). Genotypes were mostly genotype 1 (66%), genotype 3 (12%) and genotype 2 (10%). These characteristics were not different from those of the whole series of 1726 patients. A total of 176 patients (59%) were not treated, the reasons for non-treatment being medical contraindications (34%), non-compliance (25%) and normal transaminases (24%). In addition, 17% of patients declined therapy despite being considered as eligible, mainly due to fear of adverse events. Medical contraindications were psychiatric (27%), age (22%), end-stage liver disease (15%), willingness for pregnancy (13%), cardiac contraindication (7%) and others (16%). Only 123 patients (41%) were treated. A sustained viral response was observed in 41%. The treatment was interrupted in 16% for adverse events. Conclusions The majority of HCV patients are not eligible for treatment. This implies that, with current therapies, only 17% of patients referred for chronic HCV become sustained responders. Some modifications of guidelines could extend the rate of treatment (patients with normal transaminases), but an important barrier remains the patients' and the doctors' fear of adverse events