886 research outputs found

    Immune cell profiles of metastatic HER2-positive breast cancer patients according to the sites of metastasis

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    Purpose Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2-positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2-targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2-positive breast cancer treated with trastuzumab. Methods We collected all (n = 54) HER2-positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004-3.262), especially when presented as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, patients with liver metastases had low densities of CD3(+) T cells (p = 0.030) and M1-like macrophages in their primary tumours (p = 0.025). Of the other studied markers and sites, patients with pulmonary metastases had low STAB1(+)-immunosuppressive macrophage density in their primary tumours. Conclusion Our results suggest that the site of metastasis is associated with prognosis in HER2-positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.Peer reviewe

    Immune cell profiles of metastatic HER2-positive breast cancer patients according to the sites of metastasis

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    Purpose Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2-positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2-targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2-positive breast cancer treated with trastuzumab. Methods We collected all (n = 54) HER2-positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004-3.262), especially when presented as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, patients with liver metastases had low densities of CD3(+) T cells (p = 0.030) and M1-like macrophages in their primary tumours (p = 0.025). Of the other studied markers and sites, patients with pulmonary metastases had low STAB1(+)-immunosuppressive macrophage density in their primary tumours. Conclusion Our results suggest that the site of metastasis is associated with prognosis in HER2-positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.Peer reviewe

    Xylitol gummy bear snacks: a school-based randomized clinical trial

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    Background: Habitual consumption of xylitol reduces mutans streptococci (MS) levels but the effect on Lactobacillus spp. is less clear. Reduction is dependent on daily dose and frequency of consumption. For xylitol to be successfully used in prevention programs to reduce MS and prevent caries, effective xylitol delivery methods must be identified. This study examines the response of MS, specifically S. mutans/sobrinus and Lactobacillus spp., levels to xylitol delivered via gummy bears at optimal exposures. Methods: Children, first to fifth grade (n = 154), from two elementary schools in rural Washington State, USA, were randomized to xylitol 15.6 g/day (X16, n = 53) or 11.7 g/day (X12, n = 49), or maltitol 44.7 g/ day (M45, n = 52). Gummy bear snacks were pre-packaged in unit-doses, labeled with ID numbers, and distributed three times/day during school hours. No snacks were sent home. Plaque was sampled at baseline and six weeks and cultured on modified Mitis Salivarius agar for S. mutans/sobrinus and Rogosa SL agar for Lactobacillus spp. enumeration. Results: There were no differences in S. mutans/sobrinus and Lactobacillus spp. levels in plaque between the groups at baseline. At six weeks, log10 S. mutans/sobrinus levels showed significant reductions for all groups (p = 0.0001): X16 = 1.13 (SD = 1.65); X12 = 0.89 (SD = 1.11); M45 = 0.91 (SD = 1.46). Reductions were not statistically different between groups. Results for Lactobacillus spp. were mixed. Group X16 and M45 showed 0.31 (SD = 2.35), and 0.52 (SD = 2.41) log10 reductions, respectively, while X12 showed a 0.11 (SD = 2.26) log10 increase. These changes were not significant. Post-study discussions with school staff indicated that it is feasible to implement an in-classroom gummy bear snack program. Parents are accepting and children willing to consume gummy bear snacks daily. Conclusion: Reductions in S. mutans/sobrinus levels were observed after six weeks of gummy bear snack consumption containing xylitol at 11.7 or 15.6 g/day or maltitol at 44.7 g/day divided in three exposures. Lactobacillus spp. levels were essentially unchanged in all groups. These results suggest that a xylitol gummy bear snack may be an alternative to xylitol chewing gum for dental caries prevention. Positive results with high dose maltitol limit the validity of xylitol findings. A larger clinical trial is needed to confirm the xylitol results. Trial registration: [ISRCTN63160504].Supported by Grant No. U54DE14254 from the National Institute of Dental and Craniofacial Research, and Grant No. 90YD0188 from the Office of Head Start

    Effects of User Fee Exemptions on the Provision and Use of Maternal Health Services: A Review of Literature

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    User fee removal has been put forward as an approach to increasing priority health service utilization, reducing impoverishment, and ultimately reducing maternal and neonatal mortality. However, user fees are a source of facility revenue in many low-income countries, often used for purchasing drugs and supplies and paying incentives to health workers. This paper reviews evidence on the effects of user fee exemptions on maternal health service utilization, service provision, and outcomes, including both supply-side and demand-side effects. We reviewed 19 peer-reviewed research articles addressing user fee exemptions and maternal health services or outcomes published since 1990. Studies were identified through a USAIDcommissioned call for evidence, key word search, and screening process. Teams of reviewers assigned criteria- based quality scores to each paper and prepared structured narrative reviews. The grade of the evidence was found to be relatively weak, mainly from short-term, non-controlled studies. The introduction of user fee exemptions appears to have resulted in increased rates of facility-based deliveries and caesarean sections in some contexts. Impacts on maternal and neonatal mortality have not been conclusively demonstrated; exemptions for delivery care may contribute to modest reductions in institutional maternal mortality but the evidence is very weak. User fee exemptions were found to have negative, neutral, or inconclusive effects on availability of inputs, provider motivation, and quality of services. The extent to which user fee revenue lost by facilities is replaced can directly affect service provision and may have unintended consequences for provider motivation. Few studies have looked at the equity effects of fee removal, despite clear evidence that fees disproportionately burden the poor. This review highlights potential and documented benefits (increased use of maternity services) as well as risks (decreased provider motivation and quality) of user fee exemption policies for maternal health services. Governments should link user fee exemption policies with the replacement of lost revenue for facilities as well as broader health system improvements, including facility upgrades, ensured supply of needed inputs, and improved human resources for health. Removing user fees may increase uptake but will not reduce mortality proportionally if the quality of facility-based care is poor. More rigorous evaluations of both demand- and supply-side effects of mature fee exemption programmes are needed

    Survey of rehabilitation support for children 0-15 years in a rural part of Kenya

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    Abstract Purpose: Information regarding the nature, availability and distribution of rehabilitation services for children with disabilities across developing countries is scarce, and data that do exist are of variable quality. If planning and development are to progress, information about service provision is vital. The aim was to establish the scope and nature of rehabilitation support available to children with disabilities (0-15 years) and their families in rural Kenya. Method: A comprehensive sample comprising service provision in the health and special education sectors was established. Non-governmental and community-based organisations were also included. A survey of rehabilitation services was conducted through examination of service-related documentation and key informant interviews with the heads of services. Results: Rehabilitation comprised hospital-based occupational therapy, physiotherapy and orthopaedic technology; and seven special education establishments plus an education assessment resource centre. There was one non-government organisation and one community-based organisation relevant to children with disabilities. Activities focused on assessment, diagnosis and raising community awareness. Provision was challenged by inadequate staffing, resources and transport. Government funding was supplemented variously by donations and self-sufficiency initiatives. Rehabilitation approaches appeared to be informed by professional background of practitioner, rather than the needs of child. Service documentation revealed use of inconsistent recording methods. Conclusions: The data highlight the challenges of rehabilitation, demanding greater investment in personnel and their training, more material resources, improved access to the community and better recording mechanisms. Implications for Rehabilitation There needs to be greater investment in rehabilitation provision in developing countries. Consideration of community-based initiatives is required to support better access for all. In order to argue the case for improved resources, better skills and mechanisms for recording, monitoring and evaluating practice are needed

    Triangular-shaped landforms reveal subglacial drainage routes in SW Finland

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    The aim of this study is to present the first evidence of triangular-shaped till landforms and related erosional features indicative of subglacial drainage within the ice stream bed of the Scandinavian ice sheet in Finland. Previously unidentified grouped patterns of Quaternary deposits with triangular landforms can be recognized from LiDAR-based DEMs. The triangular landforms occur as segments within geomorphologically distinguishable routes that are associated with eskers. The morphological and sedimentological characteristics as well as the distribution of the triangular landforms are interpreted to involve the creep of saturated deforming till, flow and pressure fluctuations of subglacial meltwater associated with meltwater erosion. There are no existing models for the formation of this kind of large-scale drainage systems, but we claim that they represent an efficient drainage system for sub glacial meltwater transfer under high pressure conditions. Our hypothesis is that the routed, large-scale subglacial drainage systems described herein form a continuum between channelized (eskers) and more widely spread small-scale distributed subglacial drainage. Moreover, the transition from the conduit dominated drainage to triangular-shaped subglacial landforms takes place about 50-60 km from the ice margin. We provide an important contribution towards a more realistic representation of ice sheet hydrological drainage systems that could be used to improve paleoglaciological models and to simulate likely responses of ice sheets to increased meltwater production. (C) 2017 Elsevier Ltd. All rights reserved
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