Government of the United States of America

Abstract The Twentieth Century Reanalysis (20CR) project is an international effort to produce a comprehensive global atmospheric circulation dataset spanning the twentieth century, assimilating only surface pressure reports and using observed monthly sea‐surface temperature and sea‐ice distributions as boundary conditions. It is chiefly motivated by a need to provide an observational dataset with quantified uncertainties for validations of climate model simulations of the twentieth century on all time‐scales, with emphasis on the statistics of daily weather. It uses an Ensemble Kalman Filter data assimilation method with background ‘first guess’ fields supplied by an ensemble of forecasts from a global numerical weather prediction model. This directly yields a global analysis every 6 hours as the most likely state of the atmosphere, and also an uncertainty estimate of that analysis. The 20CR dataset provides the first estimates of global tropospheric variability, and of the dataset's time‐varying quality, from 1871 to the present at 6‐hourly temporal and 2° spatial resolutions. Intercomparisons with independent radiosonde data indicate that the reanalyses are generally of high quality. The quality in the extratropical Northern Hemisphere throughout the century is similar to that of current three‐day operational NWP forecasts. Intercomparisons over the second half‐century of these surface‐based reanalyses with other reanalyses that also make use of upper‐air and satellite data are equally encouraging. It is anticipated that the 20CR dataset will be a valuable resource to the climate research community for both model validations and diagnostic studies. Some surprising results are already evident. For instance, the long‐term trends of indices representing the North Atlantic Oscillation, the tropical Pacific Walker Circulation, and the Pacific–North American pattern are weak or non‐existent over the full period of record. The long‐term trends of zonally averaged precipitation minus evaporation also differ in character from those in climate model simulations of the twentieth century. Copyright © 2011 Royal Meteorological Society and Crown Copyright.

International audience

Abstract This paper provides evidence that firms with high disclosure quality ratings from financial analysis enjoy a lower effective interest cost of issuing debt. This findings is consistent with the argument that a policy of timely and detailed disclosures reduces lenders' and underwriters' perception of default risk for the disclosing firm, reducing its constant of debt. The results also indicate that the relative importance of disclosures is greater in situations where there is greater market uncertainty about the firm as reflected by the variance of stock returns. Since debt financial is an important source of external financing for publicly traded firms, the results have important implications on our understanding of the motives and consequences of corporate disclosures.

Traumatic brain injury (TBI) is an important source of morbidity in the Iraq and Afghanistan wars. Although penetrating brain injuries are more readily identified, closed brain injuries occur more commonly. Explosion or blast injury is the most common cause of war injuries. The contribution of the primary blast wave (primary blast injury) in brain injury is an area of active research. Lessons learned from the sports concussion and civilian mild TBI literature are useful. Individuals with TBI and posttraumatic stress disorder require treatment of both conditions. Families and communities need to be cognizant of the needs of these returning veterans.

April 01 2003 Is China a Status Quo Power? Alastair Iain Johnston Alastair Iain Johnston Laine Professor of China in World Affairs in the Government Department at Harvard University. Search for other works by this author on: This Site Google Scholar Author and Article Information Alastair Iain Johnston Laine Professor of China in World Affairs in the Government Department at Harvard University. Online ISSN: 1531-4804 Print ISSN: 0162-2889 © 2003 by the President and Fellows of Harvard College and the Massachusetts Institute of Technology2003 International Security (2003) 27 (4): 5–56. https://doi.org/10.1162/016228803321951081 Cite Icon Cite Permissions Share Icon Share Facebook Twitter LinkedIn Email Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Search Site Citation Alastair Iain Johnston; Is China a Status Quo Power?. International Security 2003; 27 (4): 5–56. doi: https://doi.org/10.1162/016228803321951081 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsInternational Security Search Advanced Search This content is only available as a PDF. © 2003 by the President and Fellows of Harvard College and the Massachusetts Institute of Technology2003 Article PDF first page preview Close Modal You do not currently have access to this content.

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April 01 1996 Economic Interdependence and War: A Theory of Trade Expectations Dale C. Copeland Dale C. Copeland Dale C. Copeland is Assistant Professor in the Department of Government and Foreign Affairs at the University of Virginia. Search for other works by this author on: This Site Google Scholar Author and Article Information Dale C. Copeland Dale C. Copeland is Assistant Professor in the Department of Government and Foreign Affairs at the University of Virginia. Online Issn: 1531-4804 Print Issn: 0162-2889 © 1996 by the President and Fellows of Harvard College and the Massachusetts Institute of Technology.1996 International Security (1996) 20 (4): 5–41. https://doi.org/10.1162/isec.20.4.5 Cite Icon Cite Permissions Share Icon Share Twitter LinkedIn Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Search Site Citation Dale C. Copeland; Economic Interdependence and War: A Theory of Trade Expectations. International Security 1996; 20 (4): 5–41. doi: https://doi.org/10.1162/isec.20.4.5 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsInternational Security Search Advanced Search This content is only available as a PDF. © 1996 by the President and Fellows of Harvard College and the Massachusetts Institute of Technology.1996 Article PDF first page preview Close Modal You do not currently have access to this content.

Since the Vietnam War, U.S. policymakers have worried that the American public will support military operations only if the human costs of the war, as measured in combat casualties, are minimal. Although the public is rightly averse to suffering casualties, the level of popular sensitivity to U.S. military casualties depends critically on the context in which those losses occur. The public's tolerance for the human costs of war is primarily shaped by the intersection of two crucial factors: beliefs about the rightness or wrongness of the war, and beliefs about the war's likely success. The impact of each belief depends upon the other. Ultimately, however, beliefs about the likelihood of success matter most in determining the public's willingness to tolerate U.S. military deaths in combat. A reanalysis of publicly available polls and a detailed analysis of a series of polls designed by the authors to tap into public attitudes on casualties support this conclusion.

This paper reports on a new methodology to estimate the “cost of crime.” It is adapted from the contingent valuation method used in the environmental economics literature and is itself used to estimate the public's willingness to pay for crime control programs. In a nationally representative sample of 1,300 U.S. residents, we found that the typical household would be willing to pay between $100 and $150 per year for programs that reduced specific crimes by 10 percent in their communities. This willingness amounts, collectively, to approximately $25,000 per burglary, $70,000 per serious assault, $232,000 per armed

Cyberwar has been described as a revolution in military affairs, a transformation of technology and doctrine capable of overturning the prevailing world order. This characterization of the threat from cyberwar, however, reflects a common tendency to conflate means and ends; studying what could happen in cyberspace (or anywhere else) makes little sense without considering how conflict over the internet is going to realize objectives commonly addressed by terrestrial warfare. To supplant established modes of conflict, cyberwar must be capable of furthering the political ends to which force or threats of force are commonly applied, something that in major respects cyberwar fails to do. As such, conflict over the internet is much more likely to serve as an adjunct to, rather than a substitute for, existing modes of terrestrial force. Indeed, rather than threatening existing political hierarchies, cyberwar is much more likely to simply augment the advantages of status quo powers.

BACKGROUND: Elderly patients suffer higher mortality rates after trauma than younger patients. This increased mortality is attributable to age, preexisting disease, and complications as well as injury severity. METHODS: Records from 5,139 adult patients from a Level I trauma center were retrospectively reviewed. Injury Severity Score (ISS), Revised Trauma Score (RTS), early mortality (<24 hours), and late mortality (>24 hours) were determined for elderly (> or =65 years) and younger (16-64 years) patients. Preexisting diseases and complications were identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis coding. RESULTS: Mortality in elderly patients was twice that in younger patients despite equivalent injury severity (p < 0.001), and elderly patients were more likely to suffer later death than younger patients (p < 0.005). The prevalence of preexisting disease was greater in the elderly, as was the incidence of complications. Using logistic regression, ISS, RTS, preexisting cardiovascular or liver disease, the development of cardiac, renal, or infectious complications, and geriatric status were all independently predictive of late mortality (p < 0.05). CONCLUSION: Elderly trauma patients more frequently suffer late mortality than younger patients because of the combination of injury and increased preexisting disease and complications after injury. Aggressive treatment of the elderly trauma patient is warranted; however, in the face of significant preexisting disease or complications, survival is less likely. Predictive models of survival can be developed, taking into account preexisting disease and complications as well as admission parameters such as age, ISS, and RTS, and specific risk of mortality quantitated.

Abstract We present numerical experiments to investigate axisymmetric interpretations of tropical cyclone spin‐up in a three‐dimensional model. Two mechanisms are identified for the spin‐up of the mean tangential circulation. The first involves the convergence of absolute angular momentum above the boundary layer and is a mechanism to spin up the outer circulation, i.e. to increase the vortex size. The second involves the convergence of absolute angular momentum within the boundary layer and is a mechanism to spin up the inner core. It is associated with the development of supergradient wind speeds in the boundary layer. The existence of these two mechanisms provides a plausible physical explanation for certain long‐standing observations of typhoons by Weatherford and Gray, which indicate that inner‐core changes in the azimuthal‐mean tangential wind speed often occur independently from those in the outer core. The unbalanced dynamics in the inner‐core region are important in determining the maximum radial and tangential flow speeds that can be attained, and therefore important in determining the azimuthal‐mean intensity of the vortex. We illustrate the importance of unbalanced flow in the boundary layer with a simple thought experiment. The analyses and interpretations presented are novel and support a recent hypothesis of the boundary layer in the inner‐core region. Copyright © 2009 Royal Meteorological Society

OBJECTIVE: To evaluate the safety and effectiveness of high-frequency oscillatory ventilation using a protocol designed to recruit and maintain optimal lung volume in patients with severe adult respiratory distress syndrome (ARDS). SETTING: Surgical and medical intensive care units in a tertiary care, military teaching hospital. DESIGN: A prospective, clinical study. PATIENTS: Seventeen patients, 17 yrs to 83 yrs of age, with severe ARDS (Lung Injury Score of 3.81 +/- 0.23) failing inverse ratio mechanical conventional ventilation (PaO2/FiO2 ratio of 68.6 +/- 21.6, peak inspiratory pressure of 54.3 +/- 12.7 cm H2O, positive end-expiratory pressure of 18.2 +/- 6.9 cm H2O). INTERVENTIONS: High-frequency oscillatory ventilation was instituted after varying periods of conventional ventilation (5.12 +/- 4.3 days). We employed lung volume recruitment strategy that consisted of incremental increases in mean airway pressure to achieve a PaO2 of > or = 60 torr (> or = 8.0 kPa), with an FiO2 of < or = 0.6. MEASUREMENTS AND MAIN RESULTS: High-frequency oscillator ventilator settings (FiO2, mean airway pressure, pressure amplitude of oscillation [delta P] frequency) and hemodynamic parameters (cardiac output, oxygen delivery [DO2]), mean systemic and pulmonary arterial pressures, and the oxygenation index (oxygenation index = [FiO2 x mean airway pressure x 100]/PaO2) were monitored during the transition to high-frequency oscillatory ventilation and throughout the course of the high-frequency protocol. Thirteen patients demonstrated improved gas exchange and an overall improvement in PaO2/FiO2 ratio (p < .02). Reductions in the oxygenation index (p < .01) and FiO2 (p < .02) at 12, 24, and 48 hrs after starting high-frequency oscillatory ventilation were observed. No significant compromise in cardiac output or DO2 was observed, despite a significant increase in mean airway pressure (31.2 +/- 10.3 to 34.0 +/- 6.7 cm H2O, p < .05) on high-frequency oscillatory ventilation. The overall survival rate at 30 days was 47%. A greater number of pretreatment days on conventional ventilation (p < .009) and an entry oxygenation index of > 47 (sensitivity 100%, specificity 100%) were associated with mortality. CONCLUSIONS: High-frequency oscillatory ventilation is both safe and effective in adult patients with severe ARDS failing conventional ventilation. A lung volume recruitment strategy during high-frequency oscillatory ventilation produced improved gas exchange without a compromise in DO2. These results are encouraging and support the need for a prospective, randomized trial of algorithm-controlled conventional ventilation vs. high-frequency oscillatory ventilation for adults with severe ARDS.

BACKGROUND: Chronic kidney disease is thought to be a potential risk factor for cardiovascular death. In renal-allograft recipients, cardiovascular disease is the most significant cause of death. The purpose of this study was to investigate if renal function has a significant role in determining the risk for cardiovascular death in renal-allograft recipients. METHODS: We analyzed 58,900 adult patients registered in the United States Renal Data System who received a primary renal transplant between 1988 and 1998 and who had at least 1 year of graft survival. The primary study endpoint was death from a cardiovascular event beyond 1 year of transplantation. Secondary endpoints were death caused by infections and malignancy-related deaths. Cox proportional-hazard models were used to estimate the effect of renal function on cardiovascular death, infectious death, and malignancy-related death while correcting for potential confounding variables, such as donor and recipient age, gender, race, cause of end-stage renal disease, length of dialysis before transplantation, year of transplantation, donor source and age, delayed graft function, and immunosuppressive regimen. RESULTS: Serum creatinine values at 1 year after transplantation were strongly associated with the risk for cardiovascular death. Above a serum creatinine value of 1.5 mg/dL, there was a significant and progressive increase in the risk for cardiovascular death. The risk of cardiovascular death was significantly higher when patients who lost allograft function were included in the analysis. There was an association between worsening renal function and infectious death, but there was no association between renal function and malignancy-related death. CONCLUSION: Serum creatinine at 1 year is strongly associated with the incidence of cardiovascular death independent of known risk factors.

BACKGROUND: Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors. METHODOLOGY/PRINCIPAL FINDINGS: The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes. CONCLUSIONS/ SIGNIFICANCE: The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response.

Fifty-six anterior cruciate ligament (ACL) reconstructions had a magnetic resonance scan of the ACL graft six months after operation. The impingement-free grafts (n = 26) had a low magnetic resonance signal from origin to insertion. Impinged grafts (n = 30) had an increased magnetic resonance signal confined to the distal two thirds of the graft. The location of the tibial tunnel (TT) was determined from a lateral roentgenogram. Positioning the center of the TT 12-23 mm from the anterior edge of the tibia consistently produced graft impingement and flexion contractures. Roof impingement was avoided and hyperextension was regained when the TT was centered more posteriorly within a 6-mm impingement-free zone (22-28 mm from the anterior edge of the tibia). Stability and knee extension were significantly better when the center of the TT was 2-3 mm posterior to the center of the normal ACL insertion.

This paper presents conceptually correct tests of the Heckscher-Ohlin proposition that trade in commodities can be explained in terms of an interaction between factor input requirements and factor endowments. Most prior work that claims top resent tests of this hypothesis have used intuitive but inappropriate generalizations of the traditional two by two model to deal with a multidimensional reality. Moreover, prior work has in general used measurements on only two of the three variables(trade, factor input requirements and factor endowments) that are required for a proper test of the H-O theory.We derive an exact specification of the H-O interaction in a multicountry, multicommodity, multifactor world in the form of the Heckscher-Ohlin-Vanek (H-O-V) theorem which equates the factors embodied in net trade to excess factor supplies.This theorem implies sign and rank propositions analogous to those implicitly studied by Leontief, but it also implies hypotheses about the parameters linking factor contents and factor supplies. Accordingly, we conduct tests of the sign and rank propositions as well as several parametric hypotheses which permit various assumptions about measurement errors, nonproportional consumption and technological differences. Our analysis uses separately measured data on trade, factor input requirements and endowments for twenty-seven countries and twelve factors in 1967. Tests of the Leontief type sign and rank propositions sharply reject this facet of the H-O-V model. In particular, the sign of net factor exports infrequently predicts the sign of excess factor supplies and therefore does not systematically reveal factor abundance.The results from an extended set of tests conducted in a regression context reject the H-O-V hypothesis of an exact relationship between factor contents and national factor supplies. Support is found for the H-O--V assumption of homothetic preferences, but estimates of the parameters linking factor contents and factor supplies are found to differ significantly from their theoretical values. We find there is clear evidence that the departure of the estimated coefficients from their theoretical values is importantly related to differences across countries in the matrix of factor input requirements and, by implication, to violation of the assumption of factor price equalization. We also find that errors of measurement in both trade and national factor supplies are an important reason for rejection of the H-O-V hypothesis.

Significance New antifungal drugs that act via novel mechanisms are urgently needed to combat the high mortality of invasive fungal disease and the emergence of resistance to existing therapies. We describe the discovery, structure, activity, and mechanism of action of F901318, a new antifungal agent. A member of a novel class of antifungals, the orotomides, F901318 acts via inhibition of dihydroorotate dehydrogenase, an enzyme of de novo pyrimidine biosynthesis. F901318 is currently in clinical development for the treatment of invasive aspergillosis.

This review examines neuroimaging and neurocognitive findings on alcohol-related toxicity in adolescents. Teens who meet criteria for alcohol use disorders, as well as those who engage in subdiagnostic binge drinking behaviors, often show poorer neurocognitive performance, alterations in gray and white matter brain structure, and discrepant functional brain activation patterns when compared to nonusing and demographically matched controls. Abnormalities are also observed in teens with a family history of alcoholism, and such differences in neuromaturation may leave youths at increased risk for the development of an alcohol use disorder or increased substance use severity. More prospective investigations are needed, and future work should focus on disentangling preexisting differences from dose-dependent effects of alcohol on neurodevelopment. Intervention strategies that utilize neuroimaging findings (e.g., identified weaknesses in particular neural substrates and behavioral correlates) may be helpful in both prevention and intervention campaigns for teens both pre- and postinitiation of alcohol use.

The niche is the environment in which stem cells reside and is responsible for the maintenance of unique stem cell properties such as self-renewal and an undifferentiated state. The heterogeneous populations which constitute a niche include both stem cells and surrounding differentiated cells. This network of heterogeneity is responsible for the control of the necessary pathways that function in determining stem cell fate. The concept that cancer stem cells, a subpopulation of cells responsible for tumor initiation and formation, reside in their own unique niche is quickly evolving and it is of importance to understand and identify the processes occurring within this environment. The necessary intrinsic pathways that are utilized by this cancer stem cell population to maintain both self-renewal and the ability to differentiate are believed to be a result of the environment where cancer stem cells reside. The ability of a specific cancer stem cell niche to provide the environment in which this population can flourish is a critical aspect of cancer biology that mandates intense investigation. This review focuses on current evidence demonstrating that homeostatic processes such as inflammation, epithelial to mesenchymal transition, hypoxia and angiogenesis contribute to the maintenance and control of cancer stem cell fate by providing the appropriate signals within the microenvironment. It is necessary to understand the key processes occurring within this highly specialized cancer stem cell niche to identify potential therapeutic targets that can serve as the basis for development of more effective anticancer treatments.