Hemodynamic responses to low-load blood flow restriction and unrestricted high-load resistance exercise in older women

Introduction: Blood flow restriction (BFR) during low-load resistance exercise increases muscle size similarly to high-load training, and may be an alternative to lifting heavy weights for older people at risk of sarcopenia. However, few studies have addressed the safety of such exercise in older people, or whether this is impacted by the actual exercises performed during training. This study aimed to compare the acute hemodynamic and perceptual responses during low-load BFR exercise to unrestricted low-load and high-load exercise in older women, and to determine whether these responses depend on the type of exercise performed. Methods: Fifteen older women (63–75 year) were assessed for maximal strength (1RM) in the leg press and leg extension. Participants then completed three protocols using these exercises in a randomized order: (1) low-load exercise (LL); (2) low-load exercise with BFR (LLBFR), and; (3) high-load exercise (HL). Blood pressure was assessed at baseline and after each set, and impedance cardiography measured cardiovascular function during trials. Rating of perceived exertion (RPE) and muscle soreness scores were obtained throughout trials. Results: Baseline hemodynamic values were consistent between trials. Systolic, diastolic, and mean arterial pressures were higher in LLBFR compared with HL and LL (p = 0.021). The LL condition resulted in lower heart rate (p = 0.002) and rate-pressure product (p = 0.011) responses compared with LLBFR and HL. The leg press generally conferred greater hemodynamic and perceptual demands than the leg extension for all conditions (p = 0.002). RPE was lower during LL compared with LLBFR and HL (p = 0.008), and there were no between-condition differences in perceived muscle soreness. Conclusion: The blood pressure data indicate that LLBFR causes greater stress on the vasculature than LL and HL exercise, and that the leg press was generally more demanding than the leg extension. While additional cardiovascular measures were similar between LLBFR and HL conditions, caution should be advised when prescribing BFR exercise for individuals with compromised cardiac or vascular function. Nevertheless, LLBFR and HL exercise were perceived similarly, indicating that BFR training may be viable for healthy older people

The reach of citizenship: Locating the politics of industrial air pollution in Durban and beyond

This paper develops a relational understanding of the geographies of citizenship action, using the example of environmental activism in Durban as an empirical reference point. We argue that citizenship involves an interactive dynamic shaped by different actors' capacities to project authority and influence over distance by enacting different modalities of spatial reach. Post-apartheid environmental politics illustrates how the relationship between the subjects of environmental rights and agents of obligation is both de-territorialised and re-territorialised by the activities of environmental activists. We examine the politics of attributing responsibility for urban industrial pollution in Durban, and identify two modalities of spatial reach through which environmental rights have been given weight. We conclude by emphasising that forms of transnational activism, while indicative in some respects of emergent styles of cosmopolitan citizenship, remain oriented by the goals of realizing national citizenship rights

The Balloon-Borne Large Aperture Submillimeter Telescope (BLAST) 2005: A 10 deg^2 Survey of Star Formation in Cygnus X

We present Cygnus X in a new multi-wavelength perspective based on an unbiased BLAST survey at 250, 350, and 500 micron, combined with rich datasets for this well-studied region. Our primary goal is to investigate the early stages of high mass star formation. We have detected 184 compact sources in various stages of evolution across all three BLAST bands. From their well-constrained spectral energy distributions, we obtain the physical properties mass, surface density, bolometric luminosity, and dust temperature. Some of the bright sources reaching 40 K contain well-known compact H II regions. We relate these to other sources at earlier stages of evolution via the energetics as deduced from their position in the luminosity-mass (L-M) diagram. The BLAST spectral coverage, near the peak of the spectral energy distribution of the dust, reveals fainter sources too cool (~ 10 K) to be seen by earlier shorter-wavelength surveys like IRAS. We detect thermal emission from infrared dark clouds and investigate the phenomenon of cold ``starless cores" more generally. Spitzer images of these cold sources often show stellar nurseries, but these potential sites for massive star formation are ``starless" in the sense that to date there is no massive protostar in a vigorous accretion phase. We discuss evolution in the context of the L-M diagram. Theory raises some interesting possibilities: some cold massive compact sources might never form a cluster containing massive stars; and clusters with massive stars might not have an identifiable compact cold massive precursor.Comment: 42 pages, 31 Figures, 6 table

Conflicts of Interest in Sell-side Research and The Moderating Role of Institutional Investors

Because sell-side analysts are dependent on institutional investors for performance ratings and trading commissions, we argue that analysts are less likely to succumb to investment banking or brokerage pressure in stocks highly visible to institutional investors. Examining a comprehensive sample of analyst recommendations over the 1994-2000 period, we find that analysts’ recommendations relative to consensus are positively associated with investment banking relationships and brokerage pressure, but negatively associated with the presence of institutional investor owners. The presence of institutional investors is also associated with more accurate earnings forecasts and more timely re-ratings following severe share price falls

Certifications of citizenship: the history, politics and materiality of identity documents in South Asian states and diasporas

Experiences in the post-partition Indian subcontinent refute the conventional expectation that the 'possession of citizenship enables the acquisition of documents certifying it' (Jayal, 2013, 71). Instead, identity papers of various types play a vital part in certifying and authenticating claims to citizenship. This is particularly important in a context where the history of state formation, continuous migration flows and the rise of right-wing majoritarian politics has created an uncertain situation for individuals deemed to be on the ‘margins’ of the state. The papers that constitute this special issue bring together a range of disciplinary perspectives in order to investigate the history, politics and materiality of identity documents, and to dismantle citizenship as an absolute and fixed notion, seeking instead to theorise the very mutable ‘hierarchies’ and ‘degrees’ of citizenship. Collectively they offer a valuable lens onto how migrants, refugees and socio-economically marginal individuals negotiate their relationship with the state, both within South Asia and in South Asian diaspora communities. This introduction examines the wider context of the complex intersections between state-issued identity documents and the nature of citizenship and draws out cross-cutting themes across the papers in this collection

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

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

Impedance Responses Reveal β2-Adrenergic Receptor Signaling Pluridimensionality and Allow Classification of Ligands with Distinct Signaling Profiles

The discovery that drugs targeting a single G protein-coupled receptor (GPCR) can differentially modulate distinct subsets of the receptor signaling repertoire has created a challenge for drug discovery at these important therapeutic targets. Here, we demonstrate that a single label-free assay based on cellular impedance provides a real-time integration of multiple signaling events engaged upon GPCR activation. Stimulation of the β2-adrenergic receptor (β2AR) in living cells with the prototypical agonist isoproterenol generated a complex, multi-featured impedance response over time. Selective pharmacological inhibition of specific arms of the β2AR signaling network revealed the differential contribution of Gs-, Gi- and Gβγ-dependent signaling events, including activation of the canonical cAMP and ERK1/2 pathways, to specific components of the impedance response. Further dissection revealed the essential role of intracellular Ca2+ in the impedance response and led to the discovery of a novel β2AR-promoted Ca2+ mobilization event. Recognizing that impedance responses provide an integrative assessment of ligand activity, we screened a collection of β-adrenergic ligands to determine if differences in the signaling repertoire engaged by compounds would lead to distinct impedance signatures. An unsupervised clustering analysis of the impedance responses revealed the existence of 5 distinct compound classes, revealing a richer signaling texture than previously recognized for this receptor. Taken together, these data indicate that the pluridimensionality of GPCR signaling can be captured using integrative approaches to provide a comprehensive readout of drug activity