530 research outputs found

    Specific Class I HLA Supertypes but Not HLA Zygosity or Expression Are Associated with Outcomes following HLA-Matched Allogeneic Hematopoietic Cell Transplant: HLA Supertypes Impact Allogeneic HCT Outcomes

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    Maximizing the probability of antigen presentation to T cells through diversity in HLAs can enhance immune responsiveness and translate into improved clinical outcomes, as evidenced by the association of heterozygosity and supertypes at HLA class I loci with improved survival in patients with advanced solid tumors treated with immune checkpoint inhibitors. We investigated the impact of HLA heterozygosity, supertypes, and surface expression on outcomes in adult and pediatric patients with acute myeloid leukemia (AML), myelodysplastic syndrome, acute lymphoblastic leukemia, and non-Hodgkin lymphoma who underwent 8/8 HLA-matched, T cell replete, unrelated, allogeneic hematopoietic cell transplant (HCT) from 2000 to 2015 using patient data reported to the Center for International Blood and Marrow Transplant Research. HLA class I heterozygosity and HLA expression were not associated with overall survival, relapse, transplant-related mortality (TRM), disease-free survival (DFS), and acute graft-versus-host disease following HCT. The HLA-B62 supertype was associated with decreased TRM in the entire patient cohort (hazard ratio [HR], 0.79; 95% CI, 0.69 to 0.90; P = .00053). The HLA-B27 supertype was associated with worse DFS in patients with AML (HR = 1.21; 95% CI, 1.10 to 1.32; P = .00005). These findings suggest that the survival benefit of HLA heterozygosity seen in solid tumor patients receiving immune checkpoint inhibitors does not extend to patients undergoing allogeneic HCT. Certain HLA supertypes, however, are associated with TRM and DFS, suggesting that similarities in peptide presentation between supertype members play a role in these outcomes. Beyond implications for prognosis following HCT, these findings support the further investigation of these HLA supertypes and the specific immune peptides important for transplant outcomes

    Hepatitis B Sero-Prevalence and Risk Behaviors Among Immigrant Men in a Population-Based Household Survey in Low-Income Neighborhoods of Northern California

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    Background Despite an effective vaccine, 60,000 new HBV infections were reported in the US in 2004; 95% in adults. We evaluate HBV sero-prevalence, risk behaviors and self-reported vaccination among Latino immigrant, Asian immigrant and US born low income men in five northern California counties. Methods Population based, cross sectional survey of HBV sero-prevalence and risk behaviors in men aged 18 to 35 years. Results Among 1,512 men screened, Asian immigrants were most likely to have had prior HBV infection (15.1%) and chronic infection (3.8%) compared to US born (prior 5.1%, chronic 0.6%) and Latino immigrant men (prior 2.0%, chronic 0.3%.) Reported HBV vaccination was lowest for Latino immigrants (12%) compared to Asian immigrants and US born men (35% in both.) Latino immigrants reported less educational attainment, medical insurance coverage and access to a physician in the last six months. Discussion Healthcare providers should routinely screen Asian immigrants for HBV regardless of their self reported vaccination status. Latino immigrants may comprise an important group of under-vaccinated, at risk persons in California. HBV testing and vaccination of immigrants soon after US arrival should be encouraged

    X-ray Absorption and Reflection in Active Galactic Nuclei

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    X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

    Best practice for motor imagery: a systematic literature review on motor imagery training elements in five different disciplines

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    <p>Abstract</p> <p>Background</p> <p>The literature suggests a beneficial effect of motor imagery (MI) if combined with physical practice, but detailed descriptions of MI training session (MITS) elements and temporal parameters are lacking. The aim of this review was to identify the characteristics of a successful MITS and compare these for different disciplines, MI session types, task focus, age, gender and MI modification during intervention.</p> <p>Methods</p> <p>An extended systematic literature search using 24 databases was performed for five disciplines: Education, Medicine, Music, Psychology and Sports. References that described an MI intervention that focused on motor skills, performance or strength improvement were included. Information describing 17 MITS elements was extracted based on the PETTLEP (physical, environment, timing, task, learning, emotion, perspective) approach. Seven elements describing the MITS temporal parameters were calculated: study duration, intervention duration, MITS duration, total MITS count, MITS per week, MI trials per MITS and total MI training time.</p> <p>Results</p> <p>Both independent reviewers found 96% congruity, which was tested on a random sample of 20% of all references. After selection, 133 studies reporting 141 MI interventions were included. The locations of the MITS and position of the participants during MI were task-specific. Participants received acoustic detailed MI instructions, which were mostly standardised and live. During MI practice, participants kept their eyes closed. MI training was performed from an internal perspective with a kinaesthetic mode. Changes in MI content, duration and dosage were reported in 31 MI interventions. Familiarisation sessions before the start of the MI intervention were mentioned in 17 reports. MI interventions focused with decreasing relevance on motor-, cognitive- and strength-focused tasks. Average study intervention lasted 34 days, with participants practicing MI on average three times per week for 17 minutes, with 34 MI trials. Average total MI time was 178 minutes including 13 MITS. Reporting rate varied between 25.5% and 95.5%.</p> <p>Conclusions</p> <p>MITS elements of successful interventions were individual, supervised and non-directed sessions, added after physical practice. Successful design characteristics were dominant in the Psychology literature, in interventions focusing on motor and strength-related tasks, in interventions with participants aged 20 to 29 years old, and in MI interventions including participants of both genders. Systematic searching of the MI literature was constrained by the lack of a defined MeSH term.</p

    Factors influencing participant enrolment in a diabetes prevention program in general practice: lessons from the Sydney diabetes prevention program

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    Background: The effectiveness of lifestyle interventions in reducing diabetes incidence has been well established. Little is known, however, about factors influencing the reach of diabetes prevention programs. This study examines the predictors of enrolment in the Sydney Diabetes Prevention Program (SDPP), a community-based diabetes prevention program conducted in general practice, New South Wales, Australia from 2008&ndash;2011.Methods: SDPP was an effectiveness trial. Participating general practitioners (GPs) from three Divisions of General Practice invited individuals aged 50&ndash;65 years without known diabetes to complete the Australian Type 2 Diabetes Risk Assessment tool. Individuals at high risk of diabetes were invited to participate in a lifestyle modification program. A multivariate model using generalized estimating equations to control for clustering of enrolment outcomes by GPs was used to examine independent predictors of enrolment in the program. Predictors included age, gender, indigenous status, region of birth, socio-economic status, family history of diabetes, history of high glucose, use of anti-hypertensive medication, smoking status, fruit and vegetable intake, physical activity level and waist measurement.Results: Of the 1821 eligible people identified as high risk, one third chose not to enrol in the lifestyle program. In multivariant analysis, physically inactive individuals (OR: 1.48, P = 0.004) and those with a family history of diabetes (OR: 1.67, P = 0.000) and history of high blood glucose levels (OR: 1.48, P = 0.001) were significantly more likely to enrol in the program. However, high risk individuals who smoked (OR: 0.52, P = 0.000), were born in a country with high diabetes risk (OR: 0.52, P = 0.000), were taking blood pressure lowering medications (OR: 0.80, P = 0.040) and consumed little fruit and vegetables (OR: 0.76, P = 0.047) were significantly less likely to take up the program.Conclusions: Targeted strategies are likely to be needed to engage groups such as smokers and high risk ethnic groups. Further research is required to better understand factors influencing enrolment in diabetes prevention programs in the primary health care setting, both at the GP and individual level.<br /

    The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

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    <p>Abstract</p> <p>Background</p> <p>The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Methods</p> <p>The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from <it>Spodoptera frugiperda</it>. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo.</p> <p>Results</p> <p>An <it>in vitro </it>isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An <it>in vitro </it>glass vial efficacy and mortality study against various life stages of the ticks <it>Ixodes ricinus, Rhipicephalus sanguineus </it>and <it>Dermacentor reticulatus </it>and against the flea (<it>Ctenocephalides felis</it>) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of these actives from a neck collar (compounded with 10% imidacloprid and 4.5% flumethrin) was extensively studied in dogs and cats under laboratory and field conditions. Acaricidal concentrations of the actives were found to be consistently released from the collar matrix for 8 months. None of the collar studies in dogs or cats were associated with any significant collar related adverse event.</p> <p>Conclusion</p> <p>Here we demonstrated the synergism between the pyrethroid flumethrin and the neonicotinoid imidacloprid, both provided in therapeutically relevant doses by a slow release collar matrix system over 8 months. This collar is therefore a convenient and safe tool for a long-term protection against ectoparasites.</p
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