313 research outputs found

    Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

    Get PDF
    The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

    The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

    Get PDF
    Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

    Advances in Diagnosis and Management of Atypical Spinal Infections: A Comprehensive Review

    Get PDF
    Atypical spinal infections (ASIs) of the spine are a challenging pathology to management with potentially devastating morbidity and mortality. To identify patients with atypical spinal infections, it is important to recognize the often insidious clinical and radiographic presentations, in the setting of indolent and smoldering organism growth. Trending of inflammatory markers, and culturing of organisms, is essential. Once identified, the spinal infection should be treated with antibiotics and possibly various surgical interventions including decompression and possible fusion depending on spine structural integrity and stability. Early diagnosis of ASIs and immediate treatment of debilitating conditions, such as epidural abscess, correlate with fewer neurological deficits and a shorter duration of medical treatment. There have been great advances in surgical interventions and spinal fusion techniques for patients with spinal infection. Overall, ASIs remain a perplexing pathology that could be successfully treated with early diagnosis and immediate, appropriate medical, and surgical management

    Clinical Outcomes with and without Adherence to Evidence-Based Medicine Guidelines for Lumbar Degenerative Spondylolisthesis Fusion Patients

    Get PDF
    Introduction: Degenerative lumbar spondylolisthesis (DS) patients are treated with instrumented fusion, following EBM guidelines, and typically have excellent clinical outcomes. However, not all lumbar fusion procedures adhere to EBM guidelines, typically due to a lack of prospective data. Objective: This retrospective study compared outcomes of DS lumbar fusion patients treated according to EBM guidelines (EBM concordant) to lumbar fused patients with procedures that did not have clear EBM literature that supported this treatment, the goal being to examine the value of present EBM to guide clinical care. Methods: A total of 125 DS patients were considered EBM concordant, while 21 patients were EBM discordant. Pre- and postsurgical ODI scores were collected. Clinical outcomes were stratified into substantial clinical benefit (SCB ΔODI \u3e10 points), minimal clinical importance benefit (MCID ΔODI ≥ 5 points), no MCID (ΔODI \u3c 5 points), and a group that showed no change or worsening ODI. Fisher\u27s exact and χ2 tests for categorical variables, Student\u27s t-test for continuous variables, and descriptive statistics were used. Statistical tests were computed at the 95% level of confidence. Results: Analysis of 125 degenerative spondylolisthesis patients was performed comparing preoperative and postoperative (6 months) ODI scores. ODI improved by 8 points in the EBM concordant group vs. 2.1 points in the EBM discordant group (p = 0.002). Compliance with EBM guidelines was associated with an odds ratio (OR) of 2.93 for achieving MCID ([CI]: 1.12-7.58, p = 0.027). Conclusions: Patients whose lumbar fusions met EBM criteria had better self-reported outcomes at six months than those who did not meet the requirements. A greater knowledge set is needed to help further support EBM-guided patient care

    HVEM Signalling Promotes Colitis

    Get PDF
    Background Tumor necrosis factor super family (TNFSF) members regulate important processes involved in cell proliferation, survival and differentiation and are therefore crucial for the balance between homeostasis and inflammatory responses. Several members of the TNFSF are closely associated with inflammatory bowel disease (IBD). Thus, they represent interesting new targets for therapeutic treatment of IBD. Methodology/Principal Findings We have used mice deficient in TNFSF member HVEM in experimental models of IBD to investigate its role in the disease process. Two models of IBD were employed: i) chemical-induced colitis primarily mediated by innate immune cells; and ii) colitis initiated by CD4+CD45RBhigh T cells following their transfer into immuno-deficient RAG1-/- hosts. In both models of disease the absence of HVEM resulted in a significant reduction in colitis and inflammatory cytokine production. Conclusions These data show that HVEM stimulatory signals promote experimental colitis driven by innate or adaptive immune cells

    ‘This restless enemy of all fertility’: exploring paradigms of coastal dune management in Western Europe over the last 700 years

    Get PDF
    Drifting sand has inundated settlements and damaged agricultural land along the coasts of Western Europe for the last 700 years. The need to control sand migration has been an important driver of the management of coastal sand dunes and here we analyse original archival materials to provide new insights into historically changing coastal dune management practices. Records of coastal sand movement in Denmark, The Netherlands, Britain, Ireland and France were reviewed and three distinct management approaches were identified. The ways in which these approaches have played out in space and time were examined with particular reference to records from landed estates in Britain and Ireland. We demonstrate how historical evidence can be used to inform contemporary debates on dune management strategy and practice. We propose a new place-based approach to the future management of coastal dunes that can incorporate both expert and locally produced ‘knowledges’ and that is underpinned by an understanding of how both natural forces and human interventions have shaped these dune landscapes over time

    Challenges and opportunities in the design and construction of a GIS-based emission inventory infrastructure for the Niger Delta region of Nigeria

    Get PDF
    © 2017, Springer-Verlag Berlin Heidelberg. Environmental monitoring in middle- and low-income countries is hampered by many factors which include enactment and enforcement of legislations; deficiencies in environmental data reporting and documentation; inconsistent, incomplete and unverifiable data; a lack of access to data; and technical expertise. This paper describes the processes undertaken and the major challenges encountered in the construction of the first Niger Delta Emission Inventory (NDEI) for criteria air pollutants and CO2 released from the anthropogenic activities in the region. This study focused on using publicly available government and research data. The NDEI has been designed to provide a Geographic Information System-based component of an air quality and carbon management framework. The NDEI infrastructure was designed and constructed at 1-, 10- and 20-km grid resolutions for point, line and area sources using industry standard processes and emission factors derived from activities similar to those in the Niger Delta. Due to inadequate, incomplete, potentially inaccurate and unavailable data, the infrastructure was populated with data based on a series of best possible assumptions for key emission sources. This produces outputs with variable levels of certainty, which also highlights the critical challenges in the estimation of emissions from a developing country. However, the infrastructure is functional and has the ability to produce spatially resolved emission estimates

    Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder

    Get PDF
    Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology
    • …
    corecore