The Church and Negro Progress

The marked progress of the Negro in America in which the church has been a factor has been of three general types. The first is intra-group advancement in such phases of life as education and wealth. The second is inter-group adjustments between the Negro population and the white population in such matters as economic relationships, citizenship rights and privileges, interracial contacts and fellowship. There is a third type of progress which touches both the internal and external life of the Negro group such as the cultural contributions of Negroes which have gradually been incorporated into our common life. There are, of course, the emotional attitudes, the growing group solidarity and consciousness, the development of moral customs and similar mental and social factors which the church has profoundly influenced but which are not measurable by the data and objective tests now available

T-Cell Immunity to Influenza in Older Adults: A Pathophysiological Framework for Development of More Effective Vaccines

One of the most profound public health consequences of immune senescence is reflected in an increased susceptibility to influenza and other acute respiratory illnesses, as well as a loss of influenza vaccine effectiveness in older people. Common medical conditions and mental and psychosocial health issues as well as degree of frailty and functional dependence accelerate changes associated with immune senescence. All contribute to the increased risk for complications of influenza infection, including pneumonias, heart diseases, and strokes that lead to hospitalization, disability, and death in the over 65 population. Changes in mucosal barrier mechanisms and both innate and adaptive immune functions converge in the reduced response to influenza infection, and lead to a loss of antibody-mediated protection against influenza with age. The interactions of immune senescence and reduced adaptive immune responses, persistent cytomegalovirus infection, inflammaging (chronic elevation of inflammatory cytokines), and dysregulated cytokine production, pose major challenges to the development of vaccines designed to improve T-cell-mediated immunity. In older adults, the goal of vaccination is more realistically targeted to providing clinical protection against disease rather than to inducing sterilizing immunity to infection. Standard assays of antibody titers correlate with protection against influenza illness but do not detect important changes in cellular immune mechanisms that correlate with vaccine-mediated protection against influenza in older people. This article will discuss: (i) the burden of influenza in older adults and how this relates to changes in T-cell function, (ii) age-related changes in different T-cell subsets and immunologic targets for improved influenza vaccine efficacy in older, and (iii) the development of correlates of clinical protection against influenza disease to expedite the process of new vaccine development for the 65 and older population. Ultimately, these efforts will address the public health need for improved protection against influenza in older adults and vaccine preventable disability

IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans

An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8+ T cell response to that observed in young mice. In humans, IL-2 plus IL-6 also reduces the proportion of apoptotic effector CD8+ T cells to levels resembling those of younger adults. In HLA-A2+ donors, MHC Class I tetramer staining showed that adding both exogenous IL-2 and IL-6 resulted in greater differentiation into influenza-specific effector CD8+ T cells. Since this effect of IL-2/IL-6 supplementation can be reproduced with the addition of Toll-like receptor agonists, it may be possible to exploit this mechanism and design new vaccines to improve the CD8 T cell response to influenza vaccination in older adults

Advances in applied supramolecular technologies

Supramolecular chemistry is a comparatively young field that to date has mainly been focused on building a foundation of fundamental understanding. With much progress in this area, researchers are seeking to apply this knowledge to the development of commercially viable products. In this review we seek to outline historical and recent developments within the field of supramolecular chemistry that have made the transition from laboratory to market, and to bring to light those technologies that we believe have commercial potential. In doing so we hope we may illuminate pathways to market for research currently being conducted

Advanced biological age is associated with improved antibody responses in older high-dose influenza vaccine recipients over four consecutive seasons

Background Biological aging represents a loss of integrity and functionality of physiological systems over time. While associated with an enhanced risk of adverse outcomes such as hospitalization, disability and death following infection, its role in perceived age-related declines in vaccine responses has yet to be fully elucidated. Using data and biosamples from a 4-year clinical trial comparing immune responses of standard- and high-dose influenza vaccination, we quantified biological age (BA) prior to vaccination in adults over 65 years old (n = 292) using a panel of ten serological biomarkers (albumin, alanine aminotransferase, creatinine, ferritin, free thyroxine, cholesterol, high-density lipoprotein, triglycerides, tumour necrosis factor, interleukin-6) as implemented in the BioAge R package. Hemagglutination inhibition antibody titres against influenza A/H1N1, A/H3N2 and B were quantified prior to vaccination and 4-, 10- and 20- weeks post-vaccination. Results Counter to our hypothesis, advanced BA was associated with improved post-vaccination antibody titres against the different viral types and subtypes. However, this was dependent on both vaccine dose and CMV serostatus, as associations were only apparent for high-dose recipients (d = 0.16–0.26), and were largely diminished for CMV positive high-dose recipients. Conclusions These findings emphasize two important points: first, the loss of physiological integrity related to biological aging may not be a ubiquitous driver of immune decline in older adults; and second, latent factors such as CMV infection (prevalent in up to 90% of older adults worldwide) may contribute to the heterogeneity in vaccine responses of older adults more than previously thought

South Pacific Paleogene Climate

International Ocean Discovery Program (IODP) Expedition 378 was designed to recover the first comprehensive set of Paleogene sedimentary sections from a transect of sites strategically positioned in the South Pacific to reconstruct key changes in oceanic and atmospheric circulation. These sites would have provided an unparalleled opportunity to add crucial new data and geographic coverage to existing reconstructions of Paleogene climate. In addition to the ~15 month postponement of Expedition 378 and subsequent port changes resulting in a reduction of the number of primary sites, testing and evaluation of the R/V JOIDES Resolution derrick in the weeks preceding the expedition determined that it would not support deployment of drill strings in excess of 2 km. Because of this determination, only 1 of the originally approved 7 primary sites was drilled. Expedition 378 recovered the first continuously cored, multiple-hole Paleogene sedimentary section from the southern Campbell Plateau at Site U1553. This high–southern latitude site builds on the legacy of Deep Sea Drilling Project (DSDP) Site 277, a single, partially spot cored hole, providing a unique opportunity to refine and augment existing reconstructions of the past ~66 My of climate history. This also includes the discovery of a new siliciclastic unit that had never been drilled before. As the world’s largest ocean, the Pacific Ocean is intricately linked to major changes in the global climate system. Previous drilling in the low-latitude Pacific Ocean during Ocean Drilling Program (ODP) Legs 138 and 199 and Integrated Ocean Drilling Program Expeditions 320 and 321 provided new insights into climate and carbon system dynamics, productivity changes across the zone of divergence, time-dependent calcium carbonate dissolution, bio- and magnetostratigraphy, the location of the Intertropical Convergence Zone, and evolutionary patterns for times of climatic change and upheaval. Expedition 378 in the South Pacific Ocean uniquely complements this work with a high-latitude perspective, especially because appropriate high-latitude records are unobtainable in the Northern Hemisphere of the Pacific Ocean. Site U1553 and the entire corpus of shore-based investigations will significantly contribute to the challenges of the “Climate and Ocean Change: Reading the Past, Informing the Future” theme of the IODP Science Plan (How does Earth’s climate system respond to elevated levels of atmospheric CO2? How resilient is the ocean to chemical perturbations?). Furthermore, Expedition 378 will provide material from the South Pacific Ocean in an area critical for high-latitude climate reconstructions spanning the Paleocene to late Oligocene

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5′ and 3′ half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3–6 days before symptom onset and 14–17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized

Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing

We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infection. Previous studies suggested that a single virus established productive infection, but these conclusions were tempered because of limited sampling; now, we have greatly increased our confidence in this observation through modeling the observed earliest sample diversity based on vastly more extensive sampling. Conventional sequencing of HIV-1 from acute/early infection has shown different patterns of escape at different epitopes; we investigated the earliest escapes in exquisite detail. Over 3–6 weeks, ultradeep sequencing revealed that the virus explored an extraordinary array of potential escape routes in the process of evading the earliest CD8 T-lymphocyte responses – using 454 sequencing, we identified over 50 variant forms of each targeted epitope during early immune escape, while only 2–7 variants were detected in the same samples via conventional sequencing. In contrast to the diversity seen within epitopes, non-epitope regions, including the Envelope V3 region, which was sequenced as a control in each subject, displayed very low levels of variation. In early infection, in the regions sequenced, the consensus forms did not have a fitness advantage large enough to trigger reversion to consensus amino acids in the absence of immune pressure. In one subject, a genetic bottleneck was observed, with extensive diversity at the second time point narrowing to two dominant escape forms by the third time point, all within two months of infection. Traces of immune escape were observed in the earliest samples, suggesting that immune pressure is present and effective earlier than previously reported; quantifying the loss rate of the founder virus suggests a direct role for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic shifts in the frequencies of epitope variants during the first weeks of infection revealed a complex interplay between viral fitness and immune escape

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study

<p>Abstract</p> <p>Background</p> <p>Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients.</p> <p>Methods/Design</p> <p>A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Intervention: Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group.</p> <p>Discussion</p> <p>Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group.</p> <p>We will evaluate the effectiveness of this multifactor intervention on patient adherence to inhaled drugs considering that it will be right and feasible to the clinical practice context.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISCTN18841601">ISCTN18841601</a></p