Limits to consistent on-line forecasting for ergodic time series

This study concerns problems of time-series forecasting under the weakest of assumptions. Related results are surveyed and are points of departure for the developments here, some of which are new and others are new derivations of previous findings. The contributions in this study are all negative, showing that various plausible prediction problems are unsolvable, or in other cases, are not solvable by predictors which are known to be consistent when mixing conditions hold

Barriers and facilitators to recruitment of physicians and practices for primary care health services research at one centre

<p>Abstract</p> <p>Background</p> <p>While some research has been conducted examining recruitment methods to engage physicians and practices in primary care research, further research is needed on recruitment methodology as it remains a recurrent challenge and plays a crucial role in primary care research. This paper reviews recruitment strategies, common challenges, and innovative practices from five recent primary care health services research studies in Ontario, Canada.</p> <p>Methods</p> <p>We used mixed qualitative and quantitative methods to gather data from investigators and/or project staff from five research teams. Team members were interviewed and asked to fill out a brief survey on recruitment methods, results, and challenges encountered during a recent or ongoing project involving primary care practices or physicians. Data analysis included qualitative analysis of interview notes and descriptive statistics generated for each study.</p> <p>Results</p> <p>Recruitment rates varied markedly across the projects despite similar initial strategies. Common challenges and creative solutions were reported by many of the research teams, including building a sampling frame, developing front-office rapport, adapting recruitment strategies, promoting buy-in and interest in the research question, and training a staff recruiter.</p> <p>Conclusions</p> <p>Investigators must continue to find effective ways of reaching and involving diverse and representative samples of primary care providers and practices by building personal connections with, and buy-in from, potential participants. Flexible recruitment strategies and an understanding of the needs and interests of potential participants may also facilitate recruitment.</p

Apolipoprotein E controls the development of monocyte-derived alveolar macrophages upon pulmonary inflammatory adaptation

The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal β-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high dimensional imaging, and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of Apolipoprotein E (ApoE) -dependent monocyte-derived alveolar macrophages (ApoE+CD11b+ AM). ApoE+CD11b+ AMs expressed high levels of CD11b, ApoE, Gpnmb, and Ccl6, were glycolytic, highly phagocytic, and produced large amounts of interleukin 6 upon restimulation. Functional differences were cell intrinsic and myeloid cell-specific ApoE ablation inhibited Ly6c+ monocyte to ApoE+CD11b+ AM differentiation dependent on M-CSF secretion, promoting ApoE+CD11b+ AM cell death and thus impeding ApoE+CD11b+ AM maintenance. In vivo, β-glucan-elicited ApoE+CD11b+ AMs limited the bacterial burden of Legionella pneumophilia post-infection and improved the disease outcome in vivo and ex vivo in a murine lung fibrosis model. Collectively these data identify ApoE+CD11b+ AMs generated uponenvironmental cues, under the control of ApoE signaling, as an essential determinant for lung adaptation enhancing tissue resilience