Science on a Shoestring: Building Nursing Knowledge With Limited Funding

Building the science for nursing practice has never been more important. However, shrunken federal and state research budgets mean that investigators must find alternative sources of financial support and develop projects that are less costly to carry out. New investigators often build beginning programs of research with limited funding. This article provides an overview of some cost-effective research approaches and gives suggestions for finding other sources of funding. Examples of more cost-effective research approaches include adding complementary questions to existing funded research projects; conducting primary analysis of electronic patient records and social media content; conducting secondary analysis of data from completed studies; reviewing and synthesizing previously completed research; implementing community-based participatory research; participating in collaborative research efforts such as inter-campus team research, practice-based research networks (PBRNs), and involving undergraduate and doctoral students in research efforts. Instead of relying on funding from the National Institutes of Health (NIH) and other government agencies, nurse researchers may be able to find support for research from local sources such as businesses, organizations, or clinical agencies. Investigators will increasingly have to rely on these and other creative approaches to fund and implement their research programs if granting agency budgets do not significantly expand

The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial.

INTRODUCTION: Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents. METHODS: In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs. RESULTS: Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly. CONCLUSIONS: The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02178748

Toward the Discovery of Vaccine Adjuvants: Coupling In Silico Screening and In Vitro Analysis of Antagonist Binding to Human and Mouse CCR4 Receptors

BACKGROUND: Adjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. METHODOLOGY: Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of using virtual screening to identify potential small molecule chemokine antagonists. A combination of homology modelling and molecular docking was used to create a model of the CCR4 receptor in order to investigate potential lead compounds that display antagonistic properties. Three-dimensional structure-based virtual screening of the CCR4 receptor identified 116 small molecules that were calculated to have a high affinity for the receptor; these were tested experimentally for CCR4 antagonism. Fifteen of these small molecules were shown to inhibit specifically CCR4-mediated cell migration, including that of CCR4(+) Tregs. SIGNIFICANCE: Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice

Boomerang: Rebounding the consequences of reputation feedback on crowdsourcing platforms

Paid crowdsourcing platforms suffer from low-quality workand unfair rejections, but paradoxically, most workers and requesters have high reputation scores. These inflated scores, which make high-quality work and workers difficult to find,stem from social pressure to avoid giving negative feedback. We introduce Boomerang, a reputation system for crowdsourcing that elicits more accurate feedback by rebounding the consequences of feedback directly back onto the person who gave it. With Boomerang, requesters find that their highly rated workers gain earliest access to their future tasks, and workers find tasks from their highly-rated requesters at the top of their task feed. Field experiments verify that Boomerang causes both workers and requesters to provide feedback that is more closely aligned with their private opinions. Inspired by a game-theoretic notion of incentive-compatibility, Boomerang opens opportunities for interaction design to incentivize honest reporting over strategic dishonesty

Phase Change Material for Thermotherapy of Buruli Ulcer: A Prospective Observational Single Centre Proof-of-Principle Trial

Buruli ulcer is an infection of the subcutaneous tissue leading to chronic necrotizing skin ulcers. The causative pathogen, Mycobacterium ulcerans, grows best at 30°C–33°C and not above 37°C, and this property makes the application of heat a treatment option. We achieved a breakthrough in heat treatment of Buruli ulcer by employing the phase change material sodium acetate trihydrate as a heat application system for thermotherapy, which is widely used in commercial pocket heat pads. It is easy to apply, rechargeable in hot water, non-toxic and non-hazardous to the environment. Six laboratory reconfirmed patients with ulcerative Buruli lesions were included in the proof-of-principle study and treated for four to six weeks. In patients with small ulcers, wounds healed completely without further intervention. Patients with large defects had skin grafting after successful heat treatment. Heat treatment was not associated with marked increases in local inflammation or the development of ectopic lymphoid tissue. One and a half years after completion of treatment, all patients are relapse-free. The reusable phase change material–based heat application device appears perfectly suited for use in remote Buruli ulcer–endemic areas of countries with limited resources and infrastructure

Ready-to-Use Therapeutic Food for Catch-Up Growth in Children after an Episode of Plasmodium falciparum Malaria: An Open Randomised Controlled Trial

Background: Catch-up growth after an infection is essential for children to maintain good nutritional status. To prevent malnutrition, WHO recommends that children are given one additional healthy meal per day during the 2 weeks after onset of illness. We investigated to what extent ready-to-use therapeutic food (RUTF) promotes catch-up growth in children after an acute, uncomplicated episode of Plasmodium falciparum malaria. Methods: We did an open randomised trial of children aged 6–59 months with confirmed malaria who attended a Médecins Sans Frontières-supported outpatient clinic in Katanga Province, Democratic Republic of Congo. All children received a clinical examination and malaria treatment. Patients were then randomly assigned to either an RUTF group, who received daily supplemental RUTF (a high-protein peanut-based paste) for 14 days, or to a control group, who received no supplemental food. Children were weighed at baseline and on days 14 and 28. The primary outcome was mean weight change after 14 days ’ RUTF. Analysis was by intention-to-treat. Results: 93 children received RUTF and 87 received no food supplementation. At day 14, the RUTF group had a mean weight gain of 353 g compared with 189 g in the control group (difference 164 [95%CI 52–277], p = 0.005). However, at day 28 there was no statistically significant difference between the groups (539 g versus 414 g, respectively [p = 0.053]). Similarly, rate of weight gain per kg bodyweight per day was significantly higher at day 14 in the RUTF group (2.4 g/kg pe

Lack of Evidence for the Direct Activation of Endothelial Cells by Adult Female and Microfilarial Excretory-Secretory Products

Lymphangiectasia (dilation of the lymphatic vessel (LV)) is pathognomonic for lymphatic filariasis. In both infected humans and animal models of infection, lymphangiectasia is not restricted to the site of the worm nest, but is found along the infected vessel. These observations argue that soluble products secreted by the worm could be mediating this effect by activating the lymphatic endothelial cells (LEC) lining the vessel. We tested the ability of filarial Excretory-Secretory products to activate LECs, but were unable to detect a direct effect of the Excretory-Secretory products on the activation of LEC as assessed by a variety of approaches including cellular proliferation, cell surface molecule expression and cytokine and growth factor production (although other mediators used as positive controls did induce these effects). Collectively, these results do not support the hypothesis that Excretory-Secretory products directly activate LECs

Necator americanus and Helminth Co-Infections: Further Down-Modulation of Hookworm-Specific Type 1 Immune Responses

Parasitic infections in humans are common in tropical regions and under bad housing and sanitation conditions multiple parasitic infections are the rule rather than the exception. For helminth infections, which are thought to affect almost a quarter of the world's population, most common combinations include soil-transmitted helminths, such as hookworm, roundworm, and whipworm, as well as extra-intestinal infections by schistosomes. In order to develop and test a hookworm vaccine in endemic areas, the understanding of the impact of multiple helminth infections (co-infection) on the immune response against hookworm in infected individuals is crucial. The authors report in their article, that several parameters of the cellular (T cell markers, cytokines, chemokines) and humoral immune response (e.g. IgG4 and IgE antibodies) against hookworm are significantly affected or modulated in individuals co-infected with hookworm, roundworm and/or schistosomes. These results imply that the immune response against components of a hookworm vaccine might be altered by previous contact with other helminth species in endemic areas