The scheduling of computer disk operations

There is a growing interest in the application of scheduling techniques to the two mechanical operations which are bottlenecks in the use of movable-head disk storage devices

U.S. Multinational Services Companies: Effects of Foreign Affiliate Activity on U.S. Employment

This working paper examines the effect that U.S. services firms’ establishment abroad has on domestic employment. Whereas many papers have explored the employment effects of foreign direct investment in manufacturing, few have explored the effects of services investment. We find that services multinationals’ activities abroad increase U.S. employment by promoting intrafirm exports from parent firms to their foreign affiliates. These exports support jobs at the parents’ headquarters and throughout their U.S. supply chains. Our findings are principally based on economic research and econometric analysis performed by Commission staff, services trade and investment data published by the Bureau of Economic Analysis, and employment data collected by the Bureau of Labor Statistics. In the aggregate, we find that services activities abroad support nearly 700,000 U.S. jobs. Case studies of U.S. multinationals in the banking, computer, logistics, and retail industries provide the global dimensions of U.S. MNC operations and identify domestic employment effects associated with foreign affiliate activity in each industry

Transmission of human hepatitis C virus from patients in secondary cells for long term culture

Infection by human hepatitis C virus (HCV) is the principal cause of post-transfusion hepatitis and chronic liver diseases worldwide. A reliable in vitro culture system for the isolation and analysis of this virus is not currently available, and, as a consequence, HCV pathogenesis is poorly understood. We report here the first robust in vitro system for the isolation and propagation of HCV from infected donor blood. This system involves infecting freshly prepared macrophages with HCV and then transmission of macrophage-adapted virus into freshly immortalized B-cells from human fetal cord blood. Using this system, newly isolated HCV have been replicated in vitro in continuous cultures for over 130 weeks. These isolates were also transmitted by cell-free methods into different cell types, including B-cells, T-cells and neuronal precursor cells. These secondarily infected cells also produced in vitro transmissible infectious virus. Replication of HCV-RNA was validated by RT-PCR analysis and by in situ hybridization. Although nucleic acid sequencing of the HCV isolate reported here indicates that the isolate is probably of type 1a, other HCV types have also been isolated using this system. Western blot analysis shows the synthesis of major HCV structural proteins. We present here, for the first time, a method for productively growing HCV in vitro for prolonged periods of time. This method allows studies related to understanding the replication process, viral pathogenesis, and the development of anti-HCV drugs and vaccines

Immunoreactive trypsinogen levels in newborn screened infants with an inconclusive diagnosis of cystic fibrosis.

BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction in each individual and therefore would help to identify those with CRMS/CSPID who are later at risk for meeting the criteria of CF. METHODS: In this longitudinal, prospective study, infants with CRMS/CFSPID and CF were recruited and followed in 9 CF clinics (Canada and Italy). We compared NBS IRT levels between CF and CRMS/CFSPID, and between children with CRMS/CFSPID→CF and CRMS/CFSPID→CRMS/CFSPID during the period of June 2007 to April 2016. RESULTS: Ninety eight CRMS/CFSPID and 120 CF subjects were enrolled. During the study period, 14 (14.3%) CRMS/CFSPID subjects fulfilled the diagnostic criteria for CF (CRMS/CFSPID→CF), while the diagnosis remained uncertain (CRMS/CFSPID→ CRMS/CFSPID) in 84 (85.7%) subjects. Significantly higher NBS IRT concentrations (ng/ml) were present in CF than CRMS/CFPSID (median (interquartile range): 143.8 (99.8-206.2) vs. 75.0 (61.0-105.9); P \u3c 0.0001). Infants with CRMS/CFSPID→CF (n = 14) had significantly higher NBS IRT concentrations (ng/ml) than CRMS/CFSPID→ CRMS/CFSPID (n = 83) (median (interquartile range): 108.9 (72.3-126.8) vs. 73.7(60.0-96.0); P = 0.02). CONCLUSIONS: Amongst infants who tested positive on NBS for CF, there is a gradation of elevated NBS IRT concentrations. Infants with CF have higher NBS IRT levels than CRMS/CFPSID, and higher NBS IRT concentrations were present in infants with CRMS/CFSPID→CF than CRMS/CFSPID→ CRMS/CFSPID. NBS IRT concentrations, in concert with other factors, may have the potential to predict the likelihood of CF amongst infants with CRMS/CFSPID

Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease

Over 400 variants in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) are CF-causing. CFTR modulators target variants to improve lung function, but marked variability in response exists and current therapies do not address all CF-causing variants highlighting unmet needs. Alternative epithelial ion channel/transporters such as SLC26A9 could compensate for CFTR dysfunction, providing therapeutic targets that may benefit all individuals with CF. We investigate the relationship between rs7512462, a marker of SLC26A9 activity, and lung function pre- and post-treatment with CFTR modulators in Canadian and US CF cohorts, in the general population, and in those with chronic obstructive pulmonary disease (COPD). Rs7512462 CC genotype is associated with greater lung function in CF individuals with minimal function variants (for which there are currently no approved therapies; p = 0.008); and for gating (p = 0.033) and p.Phe508del/ p.Phe508del (p = 0.006) genotypes upon treatment with CFTR modulators. In parallel, human nasal epithelia with CC and p.Phe508del/p.Phe508del after Ussing chamber analysis of a combination of approved and experimental modulator treatments show greater CFTR function (p = 0.0022). Beyond CF, rs7512462 is associated with peak expiratory flow in a meta-analysis of the UK Biobank and Spirometa Consortium (p = 2.74 × 10−44) and provides p = 0.0891 in an analysis of COPD case-control status in the UK Biobank defined by spirometry. These findings support SLC26A9 as a therapeutic target to improve lung function for all people with CF and in individuals with other obstructive lung diseases

Prospective Evaluation of TMVR for Failed Surgical Annuloplasty Rings: MITRAL Trial Valve-in-Ring Arm 1-Year Outcomes

OBJECTIVES: The authors report 1-year outcomes of high-risk patients with failed surgical annuloplasty rings undergoing transseptal mitral valve-in-ring (MViR) with the SAPIEN 3 aortic transcatheter heart valve (THV). BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study evaluating transseptal MViR with the SAPIEN 3 aortic THV in high-risk patients with failed surgical annuloplasty rings. METHODS: Prospective enrollment of high-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis and failed annuloplasty rings at 13 U.S. sites. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). RESULTS: Thirty patients were enrolled between January 2016 and October 2017 (median age 71.5 years [interquartile range: 67.0 to 76.8 years], 36.7% women, median Society of Thoracic Surgeons score 7.6% [interquartile range: 5.1% to 11.8%], 76.7% in New York Heart Association functional class III or IV). Technical success was 66.7% (driven primarily by need for a second valve in 6 patients). There was no intraprocedural mortality or conversion to surgery. The primary performance endpoint was achieved in 85.7% of survivors at 30 days (24 of 28) and 89.5% of patients alive at 1 year with echocardiographic data available (17 of 19). All-cause mortality at 30 days was 6.7% and at 1 year was 23.3%. Among survivors at 1-year follow-up, 84.2% were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.0 mm Hg (interquartile range: 4.7 to 7.3 mm Hg), and all had ≤1+ MR. CONCLUSIONS: Transseptal MViR was associated with a 30-day mortality rate lower than predicted by the Society of Thoracic Surgeons score. At 1 year, transseptal MViR was associated with symptom improvement and stable THV performance

FairPay: Adaptively Win-Win Customer Relationships

Businesses recognize the need to become more customer focused, but struggle to see how. At the same time, our logic and business models for selling digital content and services are broken. Digital relationships enable services at low cost, but we still focus on discrete transactions at prices that consumers see as exploitive. This book explains how a revolutionary approach to pricing can solve these problems. It proposes a new architecture for cooperative service relationships that is personalized and continuously adaptive. FairPay operationalizes a new logic for conducting ongoing business relationships that adaptively seek win-win value propositions in which price reflects value. At a practical level, the author explains how this can be applied to transform a range of industries -- with motivations, and guidelines for implementation in stages -- to enhance loyalty, market share, and profits. At a conceptual level, he explores how novel processes for participative co-pricing can dynamically seek agreement on win-win value propositions -- to approach optimal price discrimination over a series of transactions. FairPay applies modern behavioral economics in choice architectures that enable deep relationship marketing. An online supplement is provided

A center for humane and environmental studies

Fifth year student research paper--School of Architecture, Georgia Institute of Technolog