Sarcopenia in COPD: a systematic review and meta-analysis

COPD is associated with a progressive loss of muscle mass and function. However, there is an unmet need to define and standardise methods to estimate the prevalence of sarcopenia in COPD patients.We performed a systematic review and meta-analysis of the prevalence of this extrapulmonary manifestation in COPD patients. We searched Embase, Medline (Ovid), CINAHL (EBSCO), Web of Science, Scopus and Google Scholar for studies published up to January 17, 2019, assessing sarcopenia in COPD patients based on low muscle mass and decreased muscle function. Interventional studies, in vitro experiments, protocols or reviews and meta-analyses were excluded. We estimated heterogeneity (I2) and assessed significance (Q) using a Chi-squared test for estimates obtained from random-effects models.4465 articles were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 62 full-text articles. Finally, 10 articles (n=2565 COPD patients) were included in this systematic review and meta-analyses. Overall, the prevalence of sarcopenia in patients with COPD was 21.6% (95% CI 14.6-30.9%, I2=94%), ranging from 8% in population-based to 21% in clinic-based studies, and 63% in COPD patients residing in nursing homes.Sarcopenia is frequently observed in COPD patients, with varying prevalence across population settings. Sarcopenia in COPD should be assessed using standardised tests and cut-off points from sarcopenia consensus criteria for clinical practice and international comparisons

From the Yellow Springs to the Land of Immortality

The Yellow Springs is a vivid metaphorical reference to the final destination of a mortal being and the dwelling place of a departed one in ancient China. In the writings of philosophers, historians, and poets during the long period of Chinese history, the Yellow Springs is not only considered as an underground physical locus where a grave is situated, but also an emotionally charged space invoke grieving, longing, and memory for the departed loved ones. The subterranean dwelling at the Yellow Springs is both a destination for a departed mortal being and an intermediary place to an ideal and imaginative realm, the land of immortality where the soul would enjoy eternity. From the Yellow Springs to the Land of Immortality is an exhibition that highlights sixteen carefully selected artworks from Gettysburg College’s Special Collections; each object embodies the perceptions and ritual practices of the rich funerary culture in the historical period in China, ranging from the late second millennium BCE to the beginning of the early twentieth century. These artifacts represent various artistic traditions and fabrication techniques — including jade carving, bronze casting, glazed pottery making — and most importantly, offer a glimpse of how art and artifacts are employed as a means to connect the living with the soul of the departed one in the Yellow Springs. Archaeo- logical discoveries in the past four decades in China have provided rich information that helps contextualize the sixteen artworks, as well as intimate knowledge about how the objects might “perform” in the life and afterlife of the individuals in the past. The practice of burying goods alongside departed loved ones has had a long tradition in China. The artworks included in this exhibition catalogue, encompassing the major dynasties in Chinese history, epitomize such a practice from a historical point of view. The bronze jue of the Shang dynasty (mid-16th c.-1046 BCE), and the miniature bell, a replica of yong bronze bell of the Zhou dynasty (1045-256 BCE), are not only ceremonial paraphernalia used by elites in ancestral sacrifices during the Bronze Age, but also material manifestations of ritual and music, the very foundations of ancient Chinese civilization. Comparable examples found in Bronze Age tombs illustrate the idea to connect the deceased, often the owner of these ritual objects, to the ancestors in the netherworld as they themselves were transitioned into the role of ancestors through a series of funerary ceremonies. [excerpt]https://cupola.gettysburg.edu/artcatalogs/1034/thumbnail.jp

Decision insight into stakeholder conflict for ERN.

Participatory modeling has become an important tool in facilitating resource decision making and dispute resolution. Approaches to modeling that are commonly used in this context often do not adequately account for important human factors. Current techniques provide insights into how certain human activities and variables affect resource outcomes; however, they do not directly simulate the complex variables that shape how, why, and under what conditions different human agents behave in ways that affect resources and human interactions related to them. Current approaches also do not adequately reveal how the effects of individual decisions scale up to have systemic level effects in complex resource systems. This lack of integration prevents the development of more robust models to support decision making and dispute resolution processes. Development of integrated tools is further hampered by the fact that collection of primary data for decision-making modeling is costly and time consuming. This project seeks to develop a new approach to resource modeling that incorporates both technical and behavioral modeling techniques into a single decision-making architecture. The modeling platform is enhanced by use of traditional and advanced processes and tools for expedited data capture. Specific objectives of the project are: (1) Develop a proof of concept for a new technical approach to resource modeling that combines the computational techniques of system dynamics and agent based modeling, (2) Develop an iterative, participatory modeling process supported with traditional and advance data capture techniques that may be utilized to facilitate decision making, dispute resolution, and collaborative learning processes, and (3) Examine potential applications of this technology and process. The development of this decision support architecture included both the engineering of the technology and the development of a participatory method to build and apply the technology. Stakeholder interaction with the model and associated data capture was facilitated through two very different modes of engagement, one a standard interface involving radio buttons, slider bars, graphs and plots, while the other utilized an immersive serious gaming interface. The decision support architecture developed through this project was piloted in the Middle Rio Grande Basin to examine how these tools might be utilized to promote enhanced understanding and decision-making in the context of complex water resource management issues. Potential applications of this architecture and its capacity to lead to enhanced understanding and decision-making was assessed through qualitative interviews with study participants who represented key stakeholders in the basin

Characterization of the physical capacity in children of the Chilean national program of cystic fibrosis

Introduction: Cystic fibrosis (CF) is an inherited, progressive, multisystem disease. Better physical capacity may slow disease progression, thus improving prognosis and survival. The objective of this research was to evaluate the physical capacity of children admitted to the National CF Program of the Metropolitan Region, Chile. Patients and Method: A multicenter, cross-sectional study design was used. The inclusion criteria were children aged 6 to 12 years enrolled in the National CF Program; Tanner sexual maturity stage I, no respiratory exacerbations in the last 30 days, and no musculoskeletal pathologies. The maximum aerobic capacity was assessed through the peak oxygen uptake (VO2 peak) and determined with an incremental protocol in a magnetic cycle ergometer connected to an ergo-spirometer with which, at the same time, respiratory gases, oxygen consumption and carbon dioxide production values every 30 seconds, anaerobic threshold, and maximum workload were analyzed. The values of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and forced expiratory flows between 25% and 75% of vital capacity were assessed through ergo-spirometry. At the beginning of the ergo-spirometry, arterial oxygen saturation, respiratory rate, heart rate, blood pressure, tidal volume and the perception of lower extremity fatigue and dyspnea were recorded using the modified Borg scale. The test lasted approximately 10 minutes. Results: The clinical records of 43 children collected from six health centers were reviewed. Out of these, 29 children met inclusion criteria, and 23 were recruited. Two children were unable to participate, reducing the final subject group to 21 (13 males, 8 females). The mean age was 8.8 ± 2 years; weight 30.5 ± 10.9 kg; height 1.32 ± 0.11 m; and body mass index 17.1 ± 3.5 (z-score 0.01 ± 1.34). More than half of the children (61%) had normal weight. The obtained VO2 peak was 43.7 ± 6.5 ml/min/kg (106.7 ± 19.8% of the predictive values). Only 10% of the children had values lower than those predicted by sex and age. No correlations were found between VO2 peak and anthropometric and pulmonary function variables. Conclusion: Most of the evaluated children (90%) had physical capacity similar to healthy subjects by sex and age

A modified Delphi study of screening for fetal alcohol spectrum disorders in Australia

Background: There is little reliable information on the prevalence of fetal alcohol spectrum disorders (FASD) in Australia and no coordinated national approach to facilitate case detection. The aim of this study was to identify health professionals’ perceptions about screening for FASD in Australia. Method: A modified Delphi process was used to assess perceptions of the need for, and the process of, screening for FASD in Australia. We recruited a panel of 130 Australian health professionals with experience or expertise in FASD screening or diagnosis. A systematic review of the literature was used to develop Likert statements on screening coverage, components and assessment methods which were administered using an online survey over two survey rounds. Results: Of the panel members surveyed, 95 (73%) responded to the questions on screening in the first survey round and, of these, 81 (85%) responded to the second round. Following two rounds there was consensus agreement on the need for targeted screening at birth (76%) and in childhood (84%). Participants did not reach consensus agreement on the need for universal screening at birth (55%) or in childhood (40%). Support for targeted screening was linked to perceived constraints on service provision and the need to examine the performance, costs and benefits of screening. For targeted screening of high risk groups, we found highest agreement for siblings of known cases of FASD (96%) and children of mothers attending alcohol treatment services (93%). Participants agreed that screening for FASD primarily requires assessment of prenatal alcohol exposure at birth (86%) and in childhood (88%), and that a checklist is needed to identify the components of screening and criteria for referral at birth (84%) and in childhood (90%). Conclusions: There is an agreed need for targeted but not universal screening for FASD in Australia, and sufficient consensus among health professionals to warrant development and evaluation of standardised methods for targeted screening and referral in the Australian context. Participants emphasised the need for locally-appropriate, evidence-based approaches to facilitate case detection, and the importance of ensuring that screening and referral programs are supported by adequate diagnostic and management capacity

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

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

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

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

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types