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OBJECTIVES/GOALS: Lupus lesional skin has elevated interferon expression, is highly colonized with Staphylococcus aureus (50%) and has no FDA-approved treatment options. We decided to investigate the effect of topical antibiotics on lupus lesional skin to determine whether it affects inflammatory gene expression. METHODS/STUDY POPULATION: Adult Systemic Lupus Erythematosus (SLE) patients with skin inflammation were recruited for this study from the Michigan Lupus cohort. All patients gave informed consent approved by the University of Michigan IRB. Lesions were swabbed for S. aureus colonization and then skin biopsies were collected from the affected area. Patients were then randomized for either mupirocin treatment or VaselineTM as the control. Product was applied to the lesion thrice daily for 7 days and swab samples and biopsies were collected again. Biopsies were saved at −80 °C. RNA was isolated from the biopsies, checked for quality and RNA-sequencing was performed to determine transcriptomic changes. RESULTS/ANTICIPATED RESULTS: Our preliminary results indicate that a higher number of genes are differentially expressed (DEGs) following treatment with mupirocin (184) than VaselineTM (133). Interestingly the DEGs from the two treatments were almost completely independent with only a few that were DE in both treatments when the data were fitted to a scatter plot. Functional enrichment analysis of the data showed significant downregulation of cytokine and chemokine pathways in the mupirocin but not the VaselineTM treatment group. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary data suggests that inflammatory signaling can be reduced in lesional skin by reducing bacterial load by topical antibiotic treatment in lupus patients. This can be particularly helpful in patients who are recalcitrant to typical treatment protocols for skin inflammation. CONFLICT OF INTEREST DESCRIPTION: J.M.K. received research funding from Celgene and serves on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Eli Lilly and J.E.G. received research funding from AbbVie, SunPharma, Celgene, and Genentech and serves on advisory boards for Novartis, AbbVie, and MiRagen. The other authors have no financial conflicts of interest.
In 2012, an unexpected outbreak of Lambdina fiscellaria (Guenée) (Lepidoptera: Geometridae) occurred in the Laurentian Mountains, Québec, Canada, known for its harsh climate. We wondered whether the eggs were sufficiently cold hardy to survive there and, if so, how long this outbreak would last. Therefore, we assessed the capacity of the eggs to supercool, to tolerate short exposures to low sub-zero temperatures, or to successfully overwinter in the field. The same assays were performed with eggs from the island of Newfoundland, Newfoundland and Labrador, Canada. The mean supercooling point of eggs from the two populations increased from −40.2 °C in mid-February to −33.7 °C in mid-May. These eggs may also die at sub-zero temperatures above their supercooling point, depending on exposure durations. In the fall of 2012 when eggs were put out in the field, < 10% survived in the Laurentian Mountains, whereas > 70% survived further south. In the spring of 2013, no parasitism was detected in the population. However, the two cold waves that swept across the Laurentian Mountains the preceding winter were likely responsible for the collapse of the population. This study demonstrates that L. fiscellaria eggs may succumb to sub-zero temperatures above their supercooling point under field conditions.
From 1977 to 1999, thousands of accurate radial velocities in both hemispheres were made on a large variety of programmes with the two CORAVEL scanners. The data base of ~350000 individual observations will now be made available to complement the Gaia data.
Glacier surface mass-balance measurements on Greenland started more than a century ago, but no compilation exists of the observations from the ablation area of the ice sheet and local glaciers. Such data could be used in the evaluation of modelled surface mass balance, or to document changes in glacier melt independently from model output. Here, we present a comprehensive database of Greenland glacier surface mass-balance observations from the ablation area of the ice sheet and local glaciers. The database spans the 123 a from 1892 to 2015, contains a total of ~3000 measurements from 46 sites, and is openly accessible through the PROMICE web portal (http://www.promice.dk). For each measurement we provide X, Y and Z coordinates, starting and ending dates as well as quality flags. We give sources for each entry and for all metadata. Two thirds of the data were collected from grey literature and unpublished archive documents. Roughly 60% of the measurements were performed by the Geological Survey of Denmark and Greenland (GEUS, previously GGU). The data cover all regions of Greenland except for the southernmost part of the east coast, but also emphasize the importance of long-term time series of which there are only two exceeding 20 a. We use the data to analyse uncertainties in point measurements of surface mass balance, as well as to estimate surface mass-balance profiles for most regions of Greenland.
Landowners and game reserve managers are often faced with the decision whether to undertake consumptive (such as hunting) and/or non-consumptive (such as tourism) use of wildlife resources on their properties. Here a theoretical model was used to examine cases where the game reserve management allocated the amount of land devoted to hunting (trophy hunting) and tourism, based on three scenarios: (1) hunting is separated from tourism but wildlife is shared; (2) hunting and tourism co-exist; and (3) hunting and tourism are separated by a fence. The consumptive and non-consumptive uses are not mutually exclusive; careful planning is needed to ensure that multiple management objectives can be met. Further, the analysis indicates that the two uses may be undertaken in the same area. Whether they are spatially, or temporally separated depends on the magnitude of the consumptive use. When consumptive use is not dominant, the two are compatible in the same shared area, provided the wildlife population is sufficiently large.
Deflection missions to near-Earth asteroids will encounter non-negligible uncertainties in the physical and orbital parameters of the target object. In order to reliably assess future impact threat mitigation operations such uncertainties have to be quantified and incorporated into the mission design. The implementation of deflection demonstration missions offers the great opportunity to test our current understanding of deflection relevant uncertainties and their consequences, e.g., regarding kinetic impacts on asteroid surfaces. In this contribution, we discuss the role of uncertainties in the NEOTωIST asteroid deflection demonstration concept, a low-cost kinetic impactor design elaborated in the framework of the NEOShield project. The aim of NEOTωIST is to change the spin state of a known and well characterized near-Earth object, in this case the asteroid (25143) Itokawa. Fast events such as the production of the impact crater and ejecta are studied via cube-sat chasers and a flyby vehicle. Long term changes, for instance, in the asteroid's spin and orbit, can be assessed using ground based observations. We find that such a mission can indeed provide valuable constraints on mitigation relevant parameters. Furthermore, the here proposed kinetic impact scenarios can be implemented within the next two decades without threatening Earth's safety.
Objectives: The aim of this study was to explore stakeholders’ points of views regarding the applicability and relevance of a framework for user involvement in health technology assessment (HTA) at the local level. We tested this framework in the context of the assessment of alternative measures to restraint and seclusion among hospitalized adults and those living in long-term-care facilities.
Methods: Twenty stakeholders (health managers, user representatives, and clinicians) from seven regions of Quebec participated in a semi-structured interview. A thematic analysis of the transcribed interviews was performed.
Results: The findings highlighted the relevance and applicability of the framework to this specific HTA. According to interviewees, direct participation of users in the HTA process allows them to be part of the decision-making process. User consultation makes it possible to consider the views of a wide variety of people, such as marginalized and vulnerable groups, who do not necessarily meet the requirements for participating in HTA committees. However, some user representatives emphasized that user consultation should be integrated into a more holistic and participatory perspective. The most frequent barrier associated with user involvement in HTA was the top-down health system, which takes little account of the user's perspective.
Conclusions: The proposed framework was seen as a reference tool for making practitioners and health managers aware of the different mechanisms of user involvement in HTA and providing a structured way to classify and describe strategies. However, there is a need for more concrete instruments to guide practice and support decision making on specific strategies for user involvement in HTA at the local level.
Detailed structural studies of two lithiated metal oxides, Li2CuO2 and nanoscale LiCoO2, have been carried out using ex situ high-energy X-ray diffraction (XRD) and in situ X-ray absorption spectroscopy (XAS) with the objective of understanding structural changes that might cause capacity loss during cycling. XRD on the cuprate was studied at various states of charge and phase composition, and the bulk state was determined by Rietveld refinement and pair density function (PDF) analysis. Results showed a largely irreversible structural change of the material upon oxidation of Cu2+ as well as CuO formation. The in-situ XAS of the LiCoO2 was analyzed through a difference method to extract the changes in the local structure that occur upon cycling in both the near edge (XANES) and extended region (EXAFS). Results suggest that cycling causes site exchange of the Co and Li ions near the surface of the nanoscale LiCoO2.
This paper reports on the study of a subsidy programme that was established in Quebec for alternate housing models (AHMs), which allows private and community organisations to offer housing services within the framework of a partnership with public health-care services. The research objectives were: (a) to compare how facility characteristics and services provided by AHMs and nursing homes (NHs) differ; (b) to examine the personal characteristics of residents living in AHMs; and (c) to compare residents with similar characteristics within AHMs and NHs in terms of unmet needs, quality of care, satisfaction with care and services, and psycho-social adaptation to the residence. A cross-sectional study was undertaken with individually matched groups to assess whether AHMs meet the needs of elders in a way similar to NHs. Overall, residents in both groups had moderate to severe levels of disability and about 60 per cent had mild to severe cognitive problems. While their general features were heterogeneous, the AHMs were more comfortable and homelike than the NHs. The quality of and satisfaction with care was appropriate in both settings, although AHMs performed better. Only one-quarter of residents in both settings, however, evidenced a good level of psycho-social adaptation to their residence. This partnership approach is a good strategy to provide a useful range of housing types in communities that can respond to the needs of elders with moderate to severe disabilities.
This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04–6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2 learners in the location of cluster repair and the sometimes-exceptional treatment of s+stop clusters. We also provide evidence that accuracy rates and repairs used in early L2 cluster production show L1 influences. We conclude that early L2 learners represent a unique learner group, whose study is crucial to the understanding of phonological development.
Background: While antipsychotic (AP) medications are frequently used in long-term care, current evidence suggests that the risks may offset the benefits, necessitating periodic reassessment of their use. The aims of this present study were: (1) to assess rates of AP use five years after our first intervention to determine the long-term impact; and (2) to implement an updated AP reduction educational intervention program at the same center five years later in order to determine whether AP use could be further reduced.
Methods: Participants were residents with dementia receiving AP medication. The educational program component included separate lectures on pharmacologic and non-pharmacologic treatment of behavioral and psychological symptoms of dementia (BPSD). Completion of the Nursing Home Behavior Problems Scale (NHBPS), physician interviews concerning AP treatment plans for subjects with dementia, and AP administration and dose assessment occurred both at baseline and again between four to five months after the educational program.
Results: Of 308 long-term residents with dementia, 53 (17.2%) were receiving regular APs, primarily for agitation, aggressivity, other behavioral problems and psychosis. Of these, six died and one was transferred, leaving 46 participants. At five months, ten (21.7%) residents were no longer receiving APs and seven (15.2%) were on a lower dose; thus, 17 (37.0%) were either discontinued or on a lower dose. There was no worsening of NHBPS scores.
Conclusion: Despite the low prevalence (17.2%) of AP users at the beginning of the current study compared to that observed five years prior (30.5%), it is still possible to further decrease the proportion of users.
Résumé. Notre contribution vise à analyser l'impact des instruments juridiques sur la fabrique des politiques publiques de la mémoire dans la France contemporaine. Il s'agit de montrer en quoi les instruments juridiques peuvent développer des effets propres sur les politiques de la mémoire qui n'étaient pas prévus initialement. C'est le cas lorsque la Cour de cassation décide, lors du procès Barbie en 1983, de donner une extension juridique à la notion de crime contre l'humanité, qui va au-delà de la reconnaissance des crimes perpétrés durant le judéocide. La reconnaissance originaire de la mémoire de la Shoah, adossée juridiquement à la notion d'imprescriptibilité du crime contre l'humanité, tient lieu de matrice cognitive pour la défense d'autres causes mémorielles (mémoire de l'esclavage et reconnaissance du génocide arménien, entre autres).
Abstract. Our contribution aims at analyzing the impact of legal instruments on public policy of memory in contemporary France. This is to show how legal instruments can develop specific effects on the politics of memory that were not originally foreseen. This is the case when “La Cour de Cassation” decided, at the Klaus Barbie trial in 1983, to give an extension to the legal concept of crimes against humanity that goes beyond the recognition of crimes perpetrated during the Holocaust. The recognition memory of the Holocaust, legally backed at the notion of crimes against humanity, acts as a cognitive matrix for the defense of other memories (memory of slavery, recognition of the Armenian Genocide …).
Objectives: The aim of this study was to review international experiences of patient or public involvement in the field of health technology assessment (HTA).
Methods: A systematic review of the scientific literature was conducted. A literature search was performed across nine databases. Other literature was identified through citation tracking, government websites (HTA agencies), and Internet search engines. Characteristics of the studies, description of the activities related to patient or public involvement, impact of these activities on the HTA process, and factors facilitating or limiting involvement were abstracted independently by two reviewers.
Results: A total of 1,441 potentially relevant papers were identified by the main search strategy. Among these, seventeen papers met the inclusion criteria; other search strategies identified seven additional documents. The findings reveal that patient or public involvement in HTA activities was reported in two domains, research and HTA process. In the research domain, patients are consulted to gather evidence about their perspectives, experiences, or preferences about a health technology. These perspectives could add key dimensions to the evaluation of health technologies that might otherwise be overlooked. In the domain of the HTA process, patients or public representatives participate in different stages of this process: prioritization, evidence assessment, or dissemination of findings.
Conclusions: There are few published examples of experiences involving patients and the public in HTA. These examples show that patients' or the public's perspectives could add important dimensions to the evaluation of health technologies. However, there is a need to develop more systematic approaches to considering patients' and the public's perspectives in HTA.
The objective of the present review was to summarise the existing European published and ‘grey’ literature on the effectiveness of school-based interventions to promote a healthy diet in children (6–12 years old) and adolescents (13–18 years old). Eight electronic databases, websites and contents of key journals were systematically searched, reference lists were screened, and authors and experts in the field were contacted for studies evaluating school-based interventions promoting a healthy diet and aiming at primary prevention of obesity. The studies were included if they were published between 1 January 1990 and 31 December 2007 and reported effects on dietary behaviour or on anthropometrics. Finally, forty-two studies met the inclusion criteria: twenty-nine in children and thirteen in adolescents. In children, strong evidence of effect was found for multicomponent interventions on fruit and vegetable intakes. Limited evidence of effect was found for educational interventions on behaviour, and for environmental interventions on fruit and vegetable intakes. Interventions that specifically targeted children from lower socio-economic status groups showed limited evidence of effect on behaviour. In adolescents, moderate evidence of effect was found for educational interventions on behaviour and limited evidence of effect for multicomponent programmes on behaviour. In children and adolescents, effects on anthropometrics were often not measured, and therefore evidence was lacking or delivered inconclusive evidence. To conclude, evidence was found for the effectiveness of especially multicomponent interventions promoting a healthy diet in school-aged children in European Union countries on self-reported dietary behaviour. Evidence for effectiveness on anthropometrical obesity-related measures is lacking.
Several studies have demonstrated the efficacy of falls-prevention programs designed for community-dwelling seniors using randomized designs. However, little is known about the feasibility of implementing these programs under natural conditions and about the success of these programs when delivered under such conditions. The objectives of this paper are to (a) describe a multifactorial falls-prevention program (called Stand Up!) designed for independent community-dwelling seniors and (b) present the results of an analysis of the practicability of implementing this program in community-based settings. The program was implemented in the context of an effectiveness study in 10 community-based organizations in the Montreal metropolitan area. Data pertaining to the reach and delivery of the program as well as participation level show that a falls-prevention program addressing multiple risk factors can be successfully implemented in community-based settings.
We present the first results of an accelerator mass spectrometry (AMS) radiocarbon intercomparison program on 3 different charcoal samples collected in one of the hearths of the Megaceros gallery of Chauvet Cave (Ardèche, France). This cave, rich in parietal decoration, is important for the study of the appearance and evolution of prehistoric art because certain drawings have been 14C dated to the Aurignacian period at the beginning of the Upper Paleolithic. The new dates indicate an age of about 32,000 BP, which is consistent with this attribution and in agreement with the results from the same sector of the cave measured previously at the Laboratoire des Sciences du Climat et de l'Environnement (LSCE). Six laboratories were involved in the intercomparison. Samples were measured in 4 AMS facilities: Center for Isotope Research, Groningen University, the Netherlands; the Oxford Radiocarbon Accelerator Unit, UK; the Centre de datation par le carbone 14, Univ. Claude Bernard Lyon 1, France (measured by AMS facilities of Poznań University, Poland); and the LSCE, UMR CEA-CNRS-UVSQ, France (measured by the Leibniz-Labor of Christian-Albrechts-Universität Kiel, Germany).