Mediating on the Internet \u3cem\u3eToday and Tomorrow \u3c/em\u3e

This paper will examine Internet opportunities for mediators and mediation participants. We will examine current Internet opportunities as well as where all of this may be taking us. The author suggests that there are unique qualities and opportunities for mediators on the Internet, including cost and convenience

Smoking patterns and chronic kidney disease in US Hispanics: Hispanic Community Health Study/Study of Latinos

Intermittent smoking is prevalent among Hispanics, but little is known about whether this smoking pattern associates with increased chronic kidney disease (CKD) risk in this population. The objective of the present study is to identify patterns of exposure associated with CKD in US Hispanics

Indefinite and Bidirectional Near Infrared Nanocrystal Photoswitching

Materials whose luminescence can be switched by optical stimulation drive technologies ranging from superresolution imaging1-4, nanophotonics5, and optical data storage6-8, to targeted pharmacology, optogenetics, and chemical reactivity9. These photoswitchable probes, including organic fluorophores and proteins, are prone to photodegradation, and often require phototoxic doses of ultraviolet (UV) or visible light. Colloidal inorganic nanoparticles have significant stability advantages over existing photoswitchable materials, but the ability to switch emission bidirectionally, particularly with NIR light, has not been reported with nanoparticles. Here, we present 2-way, near-infrared (NIR) photoswitching of avalanching nanoparticles (ANPs), showing full optical control of upconverted emission using phototriggers in the NIR-I and NIR-II spectral regions useful for subsurface imaging. Employing single-step photodarkening10-13 and photobrightening12,14-18, we demonstrate indefinite photoswitching of individual nanoparticles (>1000 cycles over 7 h) in ambient or aqueous conditions without measurable photodegradation. Critical steps of the photoswitching mechanism are elucidated by modeling and by measuring the photon avalanche properties of single ANPs in both bright and dark states. Unlimited, reversible photoswitching of ANPs enables indefinitely rewritable 2D and 3D multi-level optical patterning of ANPs, as well as optical nanoscopy with sub-{\AA} localization superresolution that allows us to distinguish individual ANPs within tightly packed clusters.Comment: 15 pages, 5 figure

Documentation of body mass index and control of associated risk factors in a large primary care network

<p>Abstract</p> <p>Background</p> <p>Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.</p> <p>Methods</p> <p>We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m²), overweight (OW, 25-29.9), and obese (OB, ≥ 30). We measured documentation (yes/no) and control (above/below) of the following three risk factors: blood pressure (BP) ≤130/≤85 mmHg, low-density lipoprotein (LDL) ≤130 mg/dL (3.367 mmol/L), and fasting glucose <100 mg/dL (5.55 mmol/L) or casual glucose <200 mg/dL (11.1 mmol/L).</p> <p>Results</p> <p>BMI was documented in 48,376 patients (61%, range 34-94%), distributed as 30% OB, 34% OW, and 36% NW. Documentation of all three risk factors was higher in obesity (OB = 58%, OW = 54%, NW = 41%, p for trend <0.0001), but control of all three was lower (OB = 44%, OW = 49%, NW = 62%, p = 0.0001). The presence of cardiovascular disease (CVD) or diabetes modified some associations with obesity, and OB patients with CVD or diabetes had low rates of control of all three risk factors (CVD: OB = 49%, OW = 50%, NW = 56%; diabetes: OB = 42%, OW = 47%, NW = 48%, p < 0.0001 for adiposity-CVD or diabetes interaction).</p> <p>Conclusions</p> <p>In a large primary care network BMI documentation has been incomplete and for patients with BMI measured, risk factor control has been poorer in obese patients compared with NW, even in those with obesity and CVD or diabetes. Better knowledge of BMI could provide an opportunity for improved quality in obesity care.</p

Association of 25-hydroxyvitamin D deficiency with NT-pro BNP levels in patients with acute myocardial infarction: a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Nutritional vitamin D deficiency is an emerging risk factor for acute myocardial infarction (AMI) and heart failure. The association of 25-hydroxyvitamin D levels with N-terminal pro B-type natriuretic peptide (NT-proBNP), a robust prognostic marker for post-AMI mortality and heart failure, is unknown and could illuminate a potential pathway for adverse outcomes among post-AMI patients with 25-hydroxyvitamin D deficiency.</p> <p>Methods</p> <p>In a cross-sectional analysis, we studied 238 AMI patients from 21 U.S. centers to test the association of nutritional vitamin D (25-hydroxyvitamin D [25(OH)D]) deficiency with NT-proBNP levels. Levels of 25(OH)D levels were categorized as normal (≥30 ng/mL), insufficient (>20 - <30 ng/mL), deficient (>10 - ≤20 ng/mL), or severely deficient (≤10 ng/mL).</p> <p>Results</p> <p>Low 25(OH)D levels were found in 95.7% of AMI patients. No significant trends for higher mean baseline log NT-proBNP levels in severely deficient (6.9 ± 1.3 pg/mL), deficient (6.9 ± 1.2 pg/mL), and insufficient (6.9 ± 0.9 pg/ml) groups were observed as compared with patients having normal (6.1 ± 1.7 pg/mL) levels, <it>P </it>= 0.17. Findings were similar in the subset of patients who had follow-up NT-proBNP levels drawn at one month. In multivariate regression modeling, after adjusting for multiple covariates, 25(OH)D was not associated with NT-proBNP.</p> <p>Conclusions</p> <p>Potential associations between nutritional vitamin D deficiency and prognosis in the setting of AMI are unlikely to be mediated through NT-proBNP pathways. Future studies should examine other mechanisms, such as inflammation and vascular calcification, by which 25(OH)D deficiency could mediate adverse outcomes post-AMI.</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment