Evidence for covert attention switching from eye-movements. Reply to commentaries on Liechty et al., 2003

We argue that our research objectives in Liechty, Pieters, and Wedel (2003) are to provide generalizable insights into covert visual attention to complex, multimodal stimuli in their natural context, through inverse inference from eye-movement data. We discuss the most important issues raised by Feng (2003) and Reichle and Nelson (2003), in particular the task definition, inclusion of ad features, object-based versus space-based attention and the evidence for the where and what streams.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45760/1/11336_2005_Article_BF02295611.pd

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams

Hippo signaling is deranged in idiopathic pulmonary fibrosis and correlates with disease severity.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no cure. It is clinically characterized by a progressive and rapid decline in lung function and histologically by excess deposition of extracellular matrix. Recently, Yes associated protein (YAP) and transcriptional co-regulator with PDZ-binding domain (TAZ), co-transcriptional activators of the Hippo pathway, were identified as having increased nuclear localization in IPF, correlating with increased stiffness. Cell type(s) with dysregulated YAP/TAZ activity in vivo were not determined. Therefore, we sought to characterize YAP/TAZ signaling and investigate potential causes for its dysregulation in IPF. Materials and Methods: Normal and fibrotic (IPF or bleomycin-treated murine) lung tissue was assessed for YAP/TAZ localization by immunofluorescence. Gene set enrichment analysis (GSEA) and principal component analysis (PCA) for Hippo pathway components was performed on human lung tissue microarrays from the Lung Gene Research Consortium (LGRC). We assessed the contribution of different cell types using GSEA of microarrays from whole murine lung (Scotton et al. JCI 2009), primary fibroblasts (mFb: Tsuki et al. Am J Path 2013) and primary alveolar type II cells (mATII; Königshoff et al. JCI 2009). Potential downstream fibrotic targets of YAP/TAZ in mATII cells isolated from fibrotic tissue were found using mass spectrometry proteomics of secretomes and siRNA against YAP/TAZ. Results: We found upregulated, nuclear TAZ in human IPF, located predominantly in hyperplastic epithelial regions. GSEA confirmed upregulation of YAP/TAZ target genes in IPF. We found both murine epithelial and fibroblasts to be enriched for YAP/TAZ targets, but enhanced regulation in epithelial cells. More than 90% of the YAP/TAZ targets identified in the mATII secretome were upregulated in vitro from fibrotic mATII cells. Using an siRNA approach, we identified Ctgf and Pai1 to be regulated by YAP/TAZ in mATII cells. We found that Hippo pathway components are significantly down in IPF patients and fibrotic murine lungs. Correspondingly, IPF patients can be segregated from normal patients with high accuracy using Hippo components in PCA. We also found that several negative regulators of YAP/TAZ transcriptional activity, including Amotl2 and Lats2, significantly correlated with disease severity.   Conclusion: YAP/TAZ transcriptional activity is enhanced in mATII isolated from the bleomycin model of fibrosis and they regulate Ctgf and Pai1, both well-known markers of IPF. Hippo signaling components segregate patients with IPF using PCA and significantly correlate with disease severity. Pharmaceutical targeting of YAP/TAZ and or restoration of Hippo signaling may represent a new therapeutic strategy for IPF. &nbsp