Now showing items 1-20 of 12844

    • Revisiting the Black Box Society by rethinking the political economy of big data

      Brevini, Benedetta; Pasquale, Frank (SAGE Publications Inc., 2020-01-01)
      The Black Box Society was one of first scholarly accounts to propose a social theory of the use of data in constructing personal reputations, new media audiences, and financial power, by illuminating recurrent patterns of power and exploitation in the digital economy. While many corporations have a direct window into our lives through constant, ubiquitous data collection, our knowledge of their inner workings is often partial and incomplete. Closely guarded by private companies and inaccessible to most researchers or the broader public, too much algorithmic decision-making remains a black box to this day. Much has happened since 2015 that vindicates and challenges the book’s main themes. To answer many of the concerns raised in the volume in light of the most recent developments, we have brought together leading thinkers who have explored the interplay of politics, economics, and culture in domains ordered algorithmically by managers, bureaucrats, and technology workers. While the contributions are diverse, a unifying theme animates them. Each offers a sophisticated critique of the interplay between state and market forces in building or eroding the many layers of our common lives, as well as the privatization of spheres of reputation, search, and finance. Unsatisfied with narrow methodologies of economics or political science, they advance politico-economic analysis. They therefore succeed in unveiling the foundational role that the turn to big data has in organizing economic and social relations.
    • Contraction Phase and Force Differentially Change Motor Evoked Potential Recruitment Slope and Interhemispheric Inhibition in Young Versus Old

      Ermer, Elsa; Harcum, Stacey; Lush, Jaime; Magder, Laurence S.; Whitall, Jill; Wittenberg, George F.; Dimyan, Michael A. (Frontiers Media S.A., 2020-10-06)
      Interhemispheric interactions are important for arm coordination and hemispheric specialization. Unilateral voluntary static contraction is known to increase bilateral corticospinal motor evoked potential (MEP) amplitude. It is unknown how increasing and decreasing contraction affect the opposite limb. Since dynamic muscle contraction is more ecologically relevant to daily activities, we studied MEP recruitment using a novel method and short interval interhemispheric inhibition (IHI) from active to resting hemisphere at 4 phases of contralateral ECR contraction: Rest, Ramp Up [increasing at 25% of maximum voluntary contraction (MVC)], Execution (tonic at 50% MVC), and Ramp Down (relaxation at 25% MVC) in 42 healthy adults. We analyzed the linear portion of resting extensor carpi radialis (ECR) MEP recruitment by stimulating at multiple intensities and comparing slopes, expressed as mV per TMS stimulation level, via linear mixed modeling. In younger participants (age ≤ 30), resting ECR MEP recruitment slopes were significantly and equally larger both at Ramp Up (slope increase = 0.047, p < 0.001) and Ramp Down (slope increase = 0.031, p < 0.001) compared to rest, despite opposite directions of force change. In contrast, Active ECR MEP recruitment slopes were larger in Ramp Down than all other phases (Rest:0.184, p < 0.001; Ramp Up:0.128, p = 0.001; Execution: p = 0.003). Older (age ≥ 60) participants’ resting MEP recruitment slope was higher than younger participants across all phases. IHI did not reduce MEP recruitment slope equally in old compared to young. In conclusion, our data indicate that MEP recruitment slope in the resting limb is affected by the homologous active limb contraction force, irrespective of the direction of force change. The active arm MEP recruitment slope, in contrast, remains relatively unaffected. Older participants had steeper MEP recruitment slopes and less interhemispheric inhibition compared to younger participants.
    • Describing the density of high-level trauma centers in the 15 largest US cities

      Stey, Anne M; Byskosh, Alexandria; Etkin, Caryn; Mackersie, Robert; Stein, Deborah M; Bilimoria, Karl Y; Crandall, Marie L (BMJ Publishing Group, 2020-10-09)
      Background There has been a proliferation of urban high-level trauma centers. The aim of this study was to describe the density of high-level adult trauma centers in the 15 largest cities in the USA and determine whether density was correlated with urban social determinants of health and violence rates. Methods The largest 15 US cities by population were identified. The American College of Surgeons' (ACS) and states' department of health websites were cross-referenced for designated high-level (levels 1 and 2) trauma centers in each city. Trauma centers and associated 20 min drive radius were mapped. High-level trauma centers per square mile and per population were calculated. The distance between high-level trauma centers was calculated. Publicly reported social determinants of health and violence data were tested for correlation with trauma center density. Results Among the 15 largest cities, 14 cities had multiple high-level adult trauma centers. There was a median of one high-level trauma center per every 150 square kilometers with a range of one center per every 39 square kilometers in Philadelphia to one center per596 square kilometers in San Antonio. There was a median of one high-level trauma center per 285 034 people with a range of one center per 175 058 people in Columbus to one center per 870 044 people in San Francisco. The median minimum distance between high-level trauma centers in the 14 cities with multiple centers was 8 kilometers and ranged from 1 kilometer in Houston to 43 kilometers in San Antonio. Social determinants of health, specifically poverty rate and unemployment rate, were highly correlated with violence rates. However, there was no correlation between trauma center density and social determinants of health or violence rates. Discussion High-level trauma centers density is not correlated with social determinants of health or violence rates. Level of evidence VI. Study type Economic/decision.
    • Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017

      James, Spencer Lewis; Memiah, Peter T. N. (BMJ Publishing Group, 2020-10-01)
      BACKGROUND: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. METHODS: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). FINDINGS: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). INTERPRETATION: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care. © Author(s) (or their employer(s)) 2020.
    • Clinical features and survival outcomes in IgD myeloma: a study by Asia Myeloma Network (AMN)

      Liu, Jin; Hu, Xiaoxia; Jia, Yanchun; Lu, Jin; Lee, Jae Hoon; Kim, Kihyun; Chen, Wenming; Liu, Aijun; Liu, Yang; Chen, Qi; et al. (Springer Nature, 2020-10-20)
    • Coronavirus Vigilance and the Holidays

      Jarrell, Bruce E. (2020-10-22)
    • Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

      James, Spencer Lewis; Memiah, Peter T.N. (BMJ Publishing Group, 2020-10-01)
      BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future. © Author(s)
    • Cardiac Biomarkers and Risk of Mortality in CKD (the CRIC Study)

      Wang, Ke; Zelnick, Leila R.; Anderson, Amanda; Cohen, Jordana; Dobre, Mirela; Deo, Rajat; Feldman, Harold; Go, Alan; Hsu, Jesse; Jaar, Bernard; et al. (Elsevier Ltd., 2020-01-01)
      Introduction: Cardiovascular disease (CVD) is the leading cause of mortality among individuals with chronic kidney disease (CKD). Cardiac biomarkers of myocardial distention, injury, and inflammation may signal unique pathways underlying CVD in CKD. In this analysis, we studied the association of baseline levels and changes in 4 traditional and novel cardiac biomarkers with risk of all-cause, CV, and non-CV mortality in a large cohort of patients with CKD. Methods: Among 3664 adults with CKD enrolled in the Chronic Renal Insufficiency Cohort Study, we conducted a cohort study to examine the associations of baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac high-sensitivity troponin T (hsTnT), growth differentiation factor−15 (GDF-15), and soluble ST-2 (sST-2) with risks of all-cause and cardiovascular (CV) mortality. Among a subcohort of 842 participants, we further examined the associations between change in biomarker levels over 2 years with risk of all-cause mortality. We used Cox proportional hazards regression models and adjusted for demographics, kidney function measures, cardiovascular risk factors, and medication use. Results: After adjustment, elevated baseline levels of each cardiac biomarker were associated with increased risk of all-cause mortality: NT-proBNP (hazard ratio [HR] = 1.92, 95% confidence interval [CI] = 1.73−2.12); hsTnT (HR = 1.62, 95% CI = 1.48, 1.78]); GDF-15 (HR = 1.61, 95% CI = 1.46−1.78]); and sST-2 (HR = 1.26, CI = 1.16−1.37). Higher baseline levels of all 4 cardiac biomarkers were also associated with increased risk of CV. Declines in NT-proBNP (adjusted HR = 0.55, 95% CI = 0.36−0.86) and sST2 (HR = 0.55, 95% CI = 0.36−0.86]) over 2 years were associated with lower risk of all-cause mortality. Conclusion: In a large cohort of CKD participants, elevations of NT-proBNP, hsTnT, GDF-15, and sST-2 were independently associated with greater risks of all-cause and CV mortality.
    • Repeated sampling facilitates within- and between-subject modeling of the human sperm transcriptome to identify dynamic and stress-responsive sncRNAs

      Morgan, Christopher P; Shetty, Amol C; Chan, Jennifer C; Berger, Dara S; Ament, Seth A; Epperson, C Neill; Bale, Tracy L (Springer Nature, 2020-10-15)
      Epidemiological studies from the last century have drawn strong associations between paternal life experiences and offspring health and disease outcomes. Recent studies have demonstrated sperm small non-coding RNA (sncRNA) populations vary in response to diverse paternal insults. However, for studies in retrospective or prospective human cohorts to identify changes in paternal germ cell epigenetics in association with offspring disease risk, a framework must first be built with insight into the expected biological variation inherent in human populations. In other words, how will we know what to look for if we don’t first know what is stable and what is dynamic, and what is consistent within and between men over time? From sperm samples from a ‘normative’ cohort of healthy human subjects collected repeatedly from each subject over 6 months, 17 healthy male participants met inclusion criteria and completed donations and psychological evaluations of perceived stress monthly. sncRNAs (including miRNA, piRNA, and tRNA) isolated from mature sperm from these samples were subjected to Illumina small RNA sequencing, aligned to subtype-specific reference transcriptomes, and quantified. The repeated measures design allowed us to define both within- and between-subject variation in the expression of 254 miRNA, 194 tRNA, and 937 piRNA in sperm over time. We developed screening criteria to identify a subset of potential environmentally responsive ‘dynamic’ sperm sncRNA. Implementing complex modeling of the relationships between individual dynamic sncRNA and perceived stress states in these data, we identified 5 miRNA (including let-7f-5p and miR-181a-5p) and 4 tRNA that are responsive to the dynamics of prior stress experience and fit our established mouse model. In the current study, we aligned repeated sampling of human sperm sncRNA expression data with concurrent measures of perceived stress as a novel framework that can now be applied across a range of studies focused on diverse environmental factors able to influence germ cell programming and potentially impact offspring development. © 2020, The Author(s).
    • Endovascular model of ischemic stroke in swine guided by real-time MRI

      Golubczyk, D; Kalkowski, L; Kwiatkowska, J; Zawadzki, M; Holak, P; Glodek, J; Milewska, K; Pomianowski, A; Janowski, M; Adamiak, Z; et al. (Springer Nature, 2020-10-14)
      Modeling stroke in animals is essential for testing efficacy of new treatments; however, previous neuroprotective therapies, based on systemic delivery in rodents failed, exposing the need for model with improved clinical relevance. The purpose of this study was to develop endovascular approach for inducing ischemia in swine. To achieve that goal, we used intra-arterial administration of thrombin mixed with gadolinium and visualized the occlusion with real-time MRI. Placement of the microcatheter proximally to rete allowed trans-catheter perfusion of the ipsilateral hemisphere as visualized by contrast-enhanced perfusion MR scans. Dynamic T2*w MRI facilitated visualization of thrombin + Gd solution transiting through cerebral vasculature and persistent hyperintensities indicated occlusion. Area of trans-catheter perfusion dynamically quantified on representative slice before and after thrombin administration (22.20 ± 6.31 cm2 vs. 13.28 ± 4.71 cm2 respectively) indicated significantly reduced perfusion. ADC mapping showed evidence of ischemia as early as 27 min and follow-up T2w scans confirmed ischemic lesion (3.14 ± 1.41 cm2). Animals developed contralateral neurological deficits but were ambulatory. Our study has overcome long lasting challenge of inducing endovascular stroke model in pig. We were able to induce stroke using minimally invasive endovascular approach and observe in real-time formation of the thrombus, blockage of cerebral perfusion and eventually stroke lesion.
    • Improving Access and Quality of Health Care in the United States: Shared Goals Among Patient Advocates

      Oehrlein, Elisabeth M; Harris, Jason; Balch, Alan; Furlong, Pat; Hargis, Eric; Woolley, Mary; Perfetto, Eleanor (Adis, 2020-10-21)
    • Novel dose–response analyses of treprostinil in pulmonary arterial hypertension and its effects on six-minute walk distance and hospitalizations

      Ramani, Gautam; Cassady, Steven; Shen, Eric; Broderick, Meredith; Wasik, Allie; Sui, Qun; Nelsen, Andrew (SAGE Publications Inc., 2020-01-01)
      Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension. Apart from the inhaled formulation, there is neither a target dose nor a ceiling dose to guide clinicians using treprostinil; doses are individualized for each patient based upon tolerability and clinical improvement. Using combined data from the pivotal subcutaneous and oral treprostinil studies, we evaluated the effect of treprostinil dose on hospitalization and exercise capacity to better define the treprostinil dose–response relationship. Data from the pivotal subcutaneous and oral treprostinil studies were combined by converting oral doses to weight-based continuous doses (ng/kg/min) accounting for patient weight and bioavailability. Patients were divided into dose tertiles (lowest, middle, highest 33%) and retrospectively analyzed. Analysis 1 assessed the effect of dose on pulmonary arterial hypertension-related and all-cause hospitalizations. Analysis 2 evaluated the effects of dose on six-minute walk distance, Borg dyspnea score, and World Health Organization functional class. Results showed that, in Analysis 1, higher doses of treprostinil were associated with significantly longer times to first pulmonary arterial hypertension-related and all-cause hospitalization. In Analysis 2, there was a trend toward improvements in six-minute walk distance with higher doses. In patients with pulmonary arterial hypertension on systemic treprostinil therapy, higher doses were associated with significantly longer time to first pulmonary arterial hypertension-related and all-cause hospitalization. There was a trend toward improvements in six-minute walk distance. Collectively, these results underscore the importance of managing prostacyclin adverse events in order to achieve appropriate dose titration. Further studies are required to confirm these findings and to better characterize the dose–response relationship of treprostinil. © The Author(s) 2020.
    • Advances in hepatitis B therapeutics

      Soriano, Vicente; Barreiro, Pablo; Cachay, Edward; Kottilil, Shyamasundaran; Fernandez-Montero, José V.; de Mendoza, Carmen (SAGE Publications Inc., 2020-01-01)
      Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss. Thus, treatment has to be given lifelong to prevent viral rebound. A broad spectrum of antivirals that block the HBV life cycle at different steps are in clinical development, including entry inhibitors, cccDNA disrupters/silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors and secretion inhibitors. Some of them exhibit higher potency than current oral nucleos(t)ides. Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139. To date, only treatment with ARO-HBV and with REP-2139 have resulted in HBsAg loss in a significant proportion of patients. Combination therapies using distinct antivirals and/or immune modulators are expected to maximize treatment benefits. The current goal is to achieve a ‘functional cure’, with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes. © The Author(s), 2020.