On invariant Gibbs measures for the generalized KdV equations

International audienceWe consider the defocusing generalized KdV equations on the circle. In particular, we construct global-in-time solutions with initial data distributed according to the Gibbs measure and show that the law of the random solutions, at any time, is again given by the Gibbs measure. In handling a nonlinearity of an arbitrary high degree, we make use of the Hermite polynomials and the white noise functional

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

If you build it, they still may not come: outcomes and process of implementing a community-based integrated knowledge translation mapping innovation

<p>Abstract</p> <p>Background</p> <p>Maps and mapping tools through geographic information systems (GIS) are highly valuable for turning data into useful information that can help inform decision-making and knowledge translation (KT) activities. However, there are several challenges involved in incorporating GIS applications into the decision-making process. We highlight the challenges and opportunities encountered in implementing a mapping innovation as a KT strategy within the non-profit (public) health sector, reflecting on the processes and outcomes related to our KT innovations.</p> <p>Methods</p> <p>A case study design, whereby the case is defined as the data analyst and manager dyad (a two-person team) in selected Ontario Early Year Centres (OEYCs), was used. Working with these paired individuals, we provided a series of interventions followed by one-on-one visits to ensure that our interventions were individually tailored to personal and local decision-making needs. Data analysis was conducted through a variety of qualitative assessments, including field notes, interview data, and maps created by participants. Data collection and data analysis have been guided by the Ottawa Model of Research Use (OMRU) conceptual framework.</p> <p>Results</p> <p>Despite our efforts to remove all barriers associated with our KT innovation (maps), our results demonstrate that both individual level and systemic barriers pose significant challenges for participants. While we cannot claim a causal association between our project and increased mapping by participants, participants did report a moderate increase in the use of maps in their organization. Specifically, maps were being used in decision-making forums as a way to allocate resources, confirm tacit knowledge about community needs, make financially-sensitive decisions more transparent, evaluate programs, and work with community partners.</p> <p>Conclusions</p> <p>This project highlights the role that maps can play and the importance of communicating the importance of maps as a decision support tool. Further, it represents an integrated knowledge project in the community setting, calling to question the applicability of traditional KT approaches when community values, minimal resources, and partners play a large role in decision making. The study also takes a unique perspective--where research producers and users work as dyad-pairs in the same organization--that has been under-explored to date in KT studies.</p

Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial

BACKGROUND: The antibacterial, anti-inflammatory, and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-to-moderate disease are not available. We assessed whether azithromycin is effective in reducing hospital admission in patients with mild-to-moderate COVID-19. METHODS: This prospective, open-label, randomised superiority trial was done at 19 hospitals in the UK. We enrolled adults aged at least 18 years presenting to hospitals with clinically diagnosed, highly probable or confirmed COVID-19 infection, with fewer than 14 days of symptoms, who were considered suitable for initial ambulatory management. Patients were randomly assigned (1:1) to azithromycin (500 mg once daily orally for 14 days) plus standard care or to standard care alone. The primary outcome was death or hospital admission from any cause over the 28 days from randomisation. The primary and safety outcomes were assessed according to the intention-to-treat principle. This trial is registered at ClinicalTrials.gov (NCT04381962) and recruitment is closed. FINDINGS: 298 participants were enrolled from June 3, 2020, to Jan 29, 2021. Three participants withdrew consent and requested removal of all data, and three further participants withdrew consent after randomisation, thus, the primary outcome was assessed in 292 participants (145 in the azithromycin group and 147 in the standard care group). The mean age of the participants was 45·9 years (SD 14·9). 15 (10%) participants in the azithromycin group and 17 (12%) in the standard care group were admitted to hospital or died during the study (adjusted OR 0·91 [95% CI 0·43-1·92], p=0·80). No serious adverse events were reported. INTERPRETATION: In patients with mild-to-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospital admission or death. Our findings do not support the use of azithromycin in patients with mild-to-moderate COVID-19. FUNDING: National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford and Pfizer

Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial

Background Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. Methods Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. Results There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). Conclusions We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma

Perceptions of newly admitted undergraduate medical students on experiential training on community placements and working in rural areas of Uganda

<p>Abstract</p> <p>Background</p> <p>Uganda has an acute problem of inadequate human resources partly due to health professionals' unwillingness to work in a rural environment. One strategy to address this problem is to arrange health professional training in rural environments through community placements. Makerere University College of Health Sciences changed training of medical students from the traditional curriculum to a problem-based learning (PBL) curriculum in 2003. This curriculum is based on the SPICES model (student-centered, problem-based, integrated, community-based and services oriented). During their first academic year, students undergo orientation on key areas of community-based education, after which they are sent in interdisciplinary teams for community placements. The objective was to assess first year students' perceptions on experiential training through community placements and factors that might influence their willingness to work in rural health facilities after completion of their training.</p> <p>Methods</p> <p>The survey was conducted among 107 newly admitted first year students on the medical, nursing, pharmacy and medical radiography program students, using in-depth interview and open-ended self-administered questionnaires on their first day at the college, from October 28-30, 2008. Data was collected on socio-demographic characteristics, motivation for choosing a medical career, prior exposure to rural health facilities, willingness to have part of their training in rural areas and factors that would influence the decision to work in rural areas.</p> <p>Results</p> <p>Over 75% completed their high school from urban areas. The majority had minimal exposure to rural health facilities, yet this is where most of them will eventually have to work. Over 75% of the newly admitted students were willing to have their training from a rural area. Perceived factors that might influence retention in rural areas include the local context of work environment, support from family and friends, availability of continuing professional training for career development and support of co-workers and the community.</p> <p>Conclusion</p> <p>Many first year students at Makerere University have limited exposure to health facilities in rural areas and have concerns about eventually working there.</p

Deriving stage at diagnosis from multiple population-based sources: colorectal and lung cancer in England.

BACKGROUND: Stage at diagnosis is a strong predictor of cancer survival. Differences in stage distributions and stage-specific management help explain geographic differences in cancer outcomes. Stage information is thus essential to improve policies for cancer control. Despite recent progress, stage information is often incomplete. Data collection methods and definition of stage categories are rarely reported. These inconsistencies may result in assigning conflicting stage for single tumours and confound the interpretation of international comparisons and temporal trends of stage-specific cancer outcomes. We propose an algorithm that uses multiple routine, population-based data sources to obtain the most complete and reliable stage information possible. METHODS: Our hierarchical approach derives a single stage category per tumour prioritising information deemed of best quality from multiple data sets and various individual components of tumour stage. It incorporates rules from the Union for International Cancer Control TNM classification of malignant tumours. The algorithm is illustrated for colorectal and lung cancer in England. We linked the cancer-specific Clinical Audit data (collected from clinical multi-disciplinary teams) to national cancer registry data. We prioritise stage variables from the Clinical Audit and added information from the registry when needed. We compared stage distribution and stage-specific net survival using two sets of definitions of summary stage with contrasting levels of assumptions for dealing with missing individual TNM components. This exercise extends a previous algorithm we developed for international comparisons of stage-specific survival. RESULTS: Between 2008 and 2012, 163 915 primary colorectal cancer cases and 168 158 primary lung cancer cases were diagnosed in adults in England. Using the most restrictive definition of summary stage (valid information on all individual TNM components), colorectal cancer stage completeness was 56.6% (from 33.8% in 2008 to 85.2% in 2012). Lung cancer stage completeness was 76.6% (from 57.3% in 2008 to 91.4% in 2012). Stage distribution differed between strategies to define summary stage. Stage-specific survival was consistent with published reports. CONCLUSIONS: We offer a robust strategy to harmonise the derivation of stage that can be adapted for other cancers and data sources in different countries. The general approach of prioritising good-quality information, reporting sources of individual TNM variables, and reporting of assumptions for dealing with missing data is applicable to any population-based cancer research using stage. Moreover, our research highlights the need for further transparency in the way stage categories are defined and reported, acknowledging the limitations, and potential discrepancies of using readily available stage variables

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres