Role of Technology in Manufacturing Competitiveness

A manufacturing revolution has emerged in the past 50 years that is as significant as the industrial revolution of the 19th century. From 1950 to 2000, the average productivity growth in manufacturing in the United States was 2.8% per year, and this figure has been accelerating for the past two decades as manufacturing productivity growth has exceeded the average of other sectors by more than one percent per year (please see table below). Stated more simply, a US manufacturing worker can produce four times as much per hour today as compared with fifty years ago. This gain has resulted from competitive pressures, the advent of new technologies, and a series of product and process innovations. It has also resulted in a much higher standard of living for Americans, as products become more useful and more affordable. In order to utilize this new manufacturing capacity, U.S. firms (and others) have expanded their marketing abroad, creating rapid increase in global trade. The perception of a crisis in American manufacturing is the result of one of the most difficult realities of large gains in productivity: additional capacity almost always exceeds increased consumption. This results in an inevitable shift of labor. Industries become more productive as they mature, and competitive pressures increase. These two factors require companies to decrease their workforce and often result in movement of commodity industries overseas. The end result is a loss of jobs in the United States. Displaced workers must shift to new occupations, requiring new skills and abilities. History has shown that this shift can be either detrimental or beneficial to workers; the most important determinant of benefit is the presence of innovative new industries, which, create high value for their markets. The sustainability of growth in the U.S. manufacturing sector is based on the ability of America to continue to innovate. Innovation is the key to a vibrant U.S. manufacturing base and continued generation of new jobs

Networks for Representation: Social Capital and the Efficacy of Local Participatory Institutions

Efforts to understand the successes and limitations of civil society institutions have inspired a growing literature on social networks, social capital, and the role that social relationships play in developing group norms supporting collective action and in linking groups to network-based resources. The literature has tended to emphasize broad egocentric networks or informal networks of community organizations, largely ignoring the importance of social capital for supporting engagement of the formal participatory institutions that are arising as a way of improving stakeholder input in many cities. The extant research on community-representing organizations has tended to conceptualize social networks in largely metaphorical terms, and has not systematically investigated the manner in which political networks support their operations. This paper argues that differing forms of network resources will support distinct types of activities undertaken by participatory organizations. Our empirical analysis demonstrates that different network resources are employed in different contexts, while suggesting that civil society organizations must overcome basic organizational hurdles related to internal conflict in order to leverage latent network resources

Beating the system : accelerating commercialization of new materials

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, Technology, Management, and Policy Program, February 2005.Includes bibliographical references (p. 233-249).Over the past century, materials have faced notoriously long delays between invention and commercialization. These delays make private investment very difficult, and can prevent good materials from reaching markets. A systematic exploration of the commercial histories of major commodity thermoplastics was performed, which showed that these delays were attributable to technical deficiencies in materials and obstacles in the application value chains. Contrary to popular wisdom, material costs, competitive materials, and serendipity were much smaller factors in commercialization delay. The factors that led to insertion of plastics into applications were different from the factors that led to post-insertion growth. The major plastics showed a characteristic pattern of commercialization. First, they entered simple, small applications in which they solved new problems. They then progressed to achieve insertion in a single major application, which they continue to dominate today. Having established themselves with this application, they found insertion in a wide range of large applications. The commercialization pattern can be explained in large part by the concept of switching costs. As knowledge of a material increases, switching costs are reduced; as value chain complexity increases, switching costs increase. The earliest applications required little understanding of plastics and had simple value chains, so switching costs were low, corresponding to fast commercialization. Later applications had more complex value chains and required much more detailed understanding of the failure modes and processing parameters of the material, corresponding to high switching costs and slow commercialization. Materials can be deployed into(cont.) many markets. By strategically selecting application markets, materials producers can significantly improve the probability that new materials will be adopted and can shorten the period of commercialization. Early markets should be selected based on the ability of the material to solve unique problems and the simplicity of the application value chain. When market selection is not an option, materials producers can integrate forward in the value chain to shorten commercialization times, but capital requirements are very high. Once integrated into an application, the safest competitive position for materials is to be the lowest cost option that meets the exact needs of the application.by Christopher Scott Musso.Ph.D

Delineating the Role of Various Factors in Renal Disposition of Digoxin through Application of Physiologically Based Kidney Model to Renal Impairment Populations

Development of sub-models of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, the advantage of such models in predicting clinical observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology (Rowland Yeo et al., 2011; Sayama et al., 2014). In the current study a PBPK kidney model was developed for digoxin, accounting for the roles of organic anion transporting peptide 4C1 (OATP4C1) and P-glycoprotein (P-gp) in its tubular secretion, with the aim to investigate the impact of age and renal impairment (moderate to severe) on renal drug disposition. Initial PBPK simulations based on changes in glomerular filtration rate (GFR) underestimated the observed reduction in digoxin renal excretion clearance (CLR) in subjects with moderately impaired renal function relative to healthy. Reduction in either proximal tubule cell number or the OATP4C1 abundance in the mechanistic kidney model successfully predicted 59% decrease in digoxin CLR, in particular when these changes were proportional to reduction in GFR. In contrast, predicted proximal tubule concentration of digoxin was only sensitive to changes in the transporter expression/ million proximal tubule cells. Based on the mechanistic modelling, reduced proximal tubule cellularity and OATP4C1 abundance, and inhibition of OATP4C1-mediated transport, are proposed as possible causes of reduced digoxin renal secretion in renally impaired patients

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

BACKGROUND: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. METHODS AND RESULTS: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. CONCLUSIONS: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases

Therapeutic Hemoglobin Levels after Gene Transfer in β-Thalassemia Mice and in Hematopoietic Cells of β-Thalassemia and Sickle Cells Disease Patients

Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients

Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial

Background Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors’ clinical experience treating patients in the trial. Methods QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug. Results A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1–80) oral azacitidine treatment cycles or 6 (1–73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3–4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications. Conclusion Oral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy. Trial registration. This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012

Reverberation mapping of optical emission lines in five active galaxies

For a video summarizing the main results, see https://www.youtube.com/watch?v=KaC-jPsIY0QWe present the first results from an optical reverberation mapping campaign executed in 2014 targeting the active galactic nuclei (AGNs) MCG+08-11-011, NGC 2617, NGC 4051, 3C 382, and Mrk 374. Our targets have diverse and interesting observational properties, including a "changing look" AGN and a broad-line radio galaxy. Based on continuum-Hβ lags, we measure black hole masses for all five targets. We also obtain Hγ and He ii λ4686 lags for all objects except 3C 382. The He ii λ4686 lags indicate radial stratification of the BLR, and the masses derived from different emission lines are in general agreement. The relative responsivities of these lines are also in qualitative agreement with photoionization models. These spectra have extremely high signal-to-noise ratios (100–300 per pixel) and there are excellent prospects for obtaining velocity-resolved reverberation signatures.Publisher PDFPeer reviewe

Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes.Systematic review and meta-analysis.We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks. Comparison groups could receive placebo or oral antidiabetic drugs (OAD) including metformin, sulphonylureas (SU), or dipeptidyl peptidase 4 inhibitors (DPP-4-i). Trials were identified through electronic databases and extensive manual searches. Primary outcomes were glycated haemoglobin A1c (HbA1c) levels, serious adverse events, death, severe hypoglycaemia, ketoacidosis and CVD. Secondary outcomes were fasting plasma glucose, body weight, blood pressure, heart rate, lipids, liver function tests, creatinine and adverse events including infections. The quality of the evidence was assessed using GRADE.Meta-analysis of 34 RCTs with 9,154 patients showed that SGLT2-i reduced HbA1c compared with placebo (mean difference -0.69%, 95% confidence interval -0.75 to -0.62%). We downgraded the evidence to 'low quality' due to variability and evidence of publication bias (P = 0.015). Canagliflozin was associated with the largest reduction in HbA1c (-0.85%, -0.99% to -0.71%). There were no differences between SGLT2-i and placebo for serious adverse events. SGLT2-i increased the risk of urinary and genital tract infections and increased serum creatinine, and exerted beneficial effects on bodyweight, blood pressure, lipids and alanine aminotransferase (moderate to low quality evidence). Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence).This review includes a large number of patients with type 2 diabetes and found that SGLT2-i reduces HbA1c with a notable increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias