bluuebunny/crossref_metadata_2025 huggingface dataset:
The National Tumor Association Foundation (ANT): A 30 year old model of home palliative care
Authors: Casadio Marina , Biasco Guido , Abernethy Amy , Bonazzi Valeria , Pannuti Raffaella , Pannuti Franco
Published: June 2010

Background

Models of palliative care delivery develop within a social, cultural, and political context. This paper describes the 30-year history of the National Tumor Association (ANT), a palliative care organization founded in the Italian province of Bologna, focusing on this model of home care for palliative cancer patients and on its evaluation.

Methods

Data were collected from the 1986-2008 ANT archives and documents from the Emilia-Romagna Region Health Department, Italy. Outcomes of interest were changed in: number of patients served, performance status at admission (Karnofsky Performance Status score [KPS]), length of participation in the program (days of care provided), place of death (home vs. hospital/hospice), and satisfaction with care. Statistical methods included linear and quadratic regressions. A linear and a quadratic regressions were generated; the independent variable was the year, while the dependent one was the number of patients from 1986 to 2008. Two linear regressions were generated for patients died at home and in the hospital, respectively. For each regression, the R square, the unstandardized and standardized coefficients and related P-values were estimated.

Results

The number of patients served by ANT has increased continuously from 131 (1986) to a cumulative total of 69,336 patients (2008), at a steady rate of approximately 121 additional patients per year and with no significant gender difference. The annual number of home visits increased from 6,357 (1985) to 904,782 (2008). More ANT patients died at home than in hospice or hospital; this proportion increased from 60% (1987) to 80% (2007). The rate of growth in the number of patients dying in hospital/hospice was approximately 40 patients/year (p < 0.01), vs. approximately 177 patients/year for patients who died at home. The percentage of patients with KPS < 40 at admission decreased from 70% (2003) to 30% (2008); the percentage of patients with KPS > 40 increased. Mean days of care for patients with KPS > 40 exceeded mean days for patients with KPS < 40 (p < 0.001). Patients and caregivers reported high satisfaction with care in each year of assessment; in 2008, among 187 interviewed caregivers, 95% judged the quality of doctors' assistance, and 91% judged the quality of nurses' assistance, to be "optimal."

Conclusions

The ANT home care model of palliative care delivery has been well-received, with progressively growing numbers of patients served. It has resulted in a greater proportion of home deaths and in patients' accessing palliative care at an earlier point in the disease trajectory. Changes in ANT chronicle palliative care trends in general.
Anticipating and blocking HIV-1 escape by second generation antiviral shRNAs
Authors: Schopman Nick CT , ter Brake Olivier , Berkhout Ben
Published: June 2010

Background

RNA interference (RNAi) is an evolutionary conserved gene silencing mechanism that mediates the sequence-specific breakdown of target mRNAs. RNAi can be used to inhibit HIV-1 replication by targeting the viral RNA genome. However, the error-prone replication machinery of HIV-1 can generate RNAi-resistant variants with specific mutations in the target sequence. For durable inhibition of HIV-1 replication the emergence of such escape viruses must be controlled. Here we present a strategy that anticipates HIV-1 escape by designing 2nd generation short hairpin RNAs (shRNAs) that form a complete match with the viral escape sequences.

Results

To block the two favorite viral escape routes observed when the HIV-1 integrase gene sequence is targeted, the original shRNA inhibitor was combined with two 2nd generation shRNAs in a single lentiviral expression vector. We demonstrate in long-term viral challenge experiments that the two dominant viral escape routes were effectively blocked. Eventually, virus breakthrough did however occur, but HIV-1 evolution was skewed and forced to use new escape routes.

Conclusion

These results demonstrate the power of the 2nd generation RNAi concept. Popular viral escape routes are blocked by the 2nd generation RNAi strategy. As a consequence viral evolution was skewed leading to new escape routes. These results are of importance for a deeper understanding of HIV-1 evolution under RNAi pressure.
Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis
Authors: Güler-Yüksel Melek , Klarenbeek Naomi B , Goekoop-Ruiterman Yvonne PM , de Vries-Bouwstra Jeska K , van der Kooij Sjoerd M , Gerards Andreas H , Ronday H Karel , Huizinga Tom WJ , Dijkmans Ben AC , Allaart Cornelia F , Lems Willem F
Published: June 2010

Introduction

To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years.

Methods

In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years.

Results

68% of the patients had accelerated hand BMD loss (>-0.003 g/cm2) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage.

Conclusions

In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.
Pharmacogenetic Predictors of Adverse Events and Response to Chemotherapy in Metastatic Colorectal Cancer: Results From North American Gastrointestinal Intergroup Trial N9741
Authors: McLeod Howard L. , Sargent Daniel J. , Marsh Sharon , Green Erin M. , King Cristi R. , Fuchs Charles S. , Ramanathan Ramesh K. , Williamson Stephen K. , Findlay Brian P. , Thibodeau Stephen N. , Grothey Axel , Morton Roscoe F. , Goldberg Richard M.
Published: June 2010

Purpose

With three available chemotherapy drugs for advanced colorectal cancer (CRC), response rate (RR) and survival outcomes have improved with associated morbidity, accentuating the need for tools to select optimal individualized treatment. Pharmacogenetics identifies the likelihood of adverse events or response based on variants in genes involved in drug transport, metabolism, and cellular targets.

Patients and Methods

Germline DNA was extracted from 520 patients on the North American Gastrointestinal Intergroup N9741 study. Three study arms were evaluated: IFL (fluorouracil [FU] + irinotecan [IRN]), FOLFOX (FU + oxaliplatin), and IROX (IRN + oxaliplatin). Information on adverse events, response, and disease-free survival was available. Thirty-four variants in 15 candidate genes for analysis based on previous associations with adverse events or outcome were assessed. Genotyping was performed using pyrosequencing.

Results

All variants were polymorphic. The homozygous UGT1A1*28 allele observed in 9% of patients was associated with risk of grade 4 neutropenia in patients on IROX (55% v 15%; P = .002). Deletion in GSTM1 was associated with grade 4 neutropenia after FOLFOX (28% v 16%; P = .02). Patients with a homozygous variant genotype for GSTP1 were more likely to discontinue FOLFOX because of neurotoxicity (24% v 10%; P = .01). The presence of a CYP3A5 variant was significantly associated with RR on IFL (29% v 60%; P = .0074). Most previously published genotype-toxicity or -efficacy relationships were not validated in this study.

Conclusion

This study provides a platform to evaluate pharmacogenetic predictors of response or severe adverse events in advanced CRC. Pharmacogenetic studies can be conducted in multicenter trials, and our findings demonstrate that with continued research, clinical application is practical.
Phase III Trial Comparing Docetaxel and Cisplatin Combination Chemotherapy With Mitomycin, Vindesine, and Cisplatin Combination Chemotherapy With Concurrent Thoracic Radiotherapy in Locally Advanced Non–Small-Cell Lung Cancer: OLCSG 0007
Authors: Segawa Yoshihiko , Kiura Katsuyuki , Takigawa Nagio , Kamei Haruhito , Harita Shingo , Hiraki Shunkichi , Watanabe Yoichi , Sugimoto Keisuke , Shibayama Takuo , Yonei Toshiro , Ueoka Hiroshi , Takemoto Mitsuhiro , Kanazawa Susumu , Takata Ichiro , Nogami Naoyuki , Hotta Katsuyuki , Hiraki Akio , Tabata Masahiro , Matsuo Keitaro , Tanimoto Mitsune
Published: June 2010

Purpose

To demonstrate the efficacy of docetaxel and cisplatin (DP) chemotherapy with concurrent thoracic radiotherapy (TRT) for patients with locally advanced non–small-cell lung cancer (LA-NSCLC).

Patients and Methods

Patients age 75 years or younger with LA-NSCLC, stratified by performance status, stage, and institution, were randomly assigned to two arms consisting of DP (docetaxel 40 mg/m2 and cisplatin 40 mg/m2 on days 1, 8, 29, and 36) or mitomycin, vindesine, and cisplatin (MVP) chemotherapy with concurrent TRT.

Results

Between July 2000 and July 2005, 200 patients were allocated into either the DP or MVP arm. The survival time at 2 years, a primary end point, was favorable to the DP arm (P = .059 by a stratified log-rank test as a planned analysis and P = .044 by an early-period, weighted log-rank as an unplanned analysis). There was a trend toward improved response rate, 2-year survival rate, median progression-free time, and median survival in the DP arm (78.8%, 60.3%,13.4 months, and 26.8 months, respectively) compared with the MVP arm (70.3%, 48.1%, 10.5 months, and 23.7 months, respectively), which was not statistically significant (P > .05). Grade 3 febrile neutropenia occurred more often in the MVP arm than in the DP arm (39% v 22%, respectively; P = .012), and grade 3 to 4 radiation esophagitis was likely to be more common in the DP arm than in the MVP arm (14% v 6%, P = .056).

Conclusion

DP chemotherapy combined with concurrent TRT is an alternative to MVP chemotherapy for patients with LA-NSCLC.
American Society of Clinical Oncology Clinical Practice Guideline on Uses of Serum Tumor Markers in Adult Males With Germ Cell Tumors
Authors: Gilligan Timothy D. , Seidenfeld Jerome , Basch Ethan M. , Einhorn Lawrence H. , Fancher Timothy , Smith David C. , Stephenson Andrew J. , Vaughn David J. , Cosby Roxanne , Hayes Daniel F.
Published: June 2010

Purpose

To provide recommendations on appropriate uses for serum markers of germ cell tumors (GCTs).

Methods

Searches of MEDLINE and EMBASE identified relevant studies published in English. Primary outcomes included marker accuracy to predict the impact of decisions on outcomes. Secondary outcomes included proportions of patients with elevated markers and statistical tests of elevations as prognostic factors. An expert panel developed consensus guidelines based on data from 82 reports.

Results

No studies directly compared outcomes of decisions with versus without marker assays. The search identified few prospective studies and no randomized controlled trials; most were retrospective series. Lacking data on primary outcomes, most Panel recommendations are based on secondary outcomes (relapse rates and time to relapse).

Recommendations

The Panel recommended against using markers to screen for GCTs, to decide whether orchiectomy is indicated, or to select treatment for patients with cancer of unknown primary. To stage patients with testicular nonseminomas, the Panel recommended measuring three markers (α-fetoprotein [AFP], human chorionic gonadotropin [hCG], and lactate dehydrogenase [LDH]) before and after orchiectomy and before chemotherapy for those with extragonadal nonseminomas. They also recommended measuring AFP and hCG shortly before retroperitoneal lymph node dissection and at the start of each chemotherapy cycle for nonseminoma, and periodically to monitor for relapse. The Panel recommended measuring postorchiectomy hCG and LDH for patients with seminoma and preorchiectomy elevations. They recommended against using markers to guide or monitor treatment for seminoma or to detect relapse in those treated for stage I. However, they recommended measuring hCG and AFP to monitor for relapse in patients treated for advanced seminoma.
Mesoderm migration in Drosophila is a multi-step process requiring FGF signaling and integrin activity
Authors: McMahon Amy , Reeves Gregory T. , Supatto Willy , Stathopoulos Angelike
Published: June 2010

Migration is a complex, dynamic process that has largely been studied using qualitative or static approaches. As technology has improved, we can now take quantitative approaches towards understanding cell migration using in vivo imaging and tracking analyses. In this manner, we have established a four-step model of mesoderm migration during Drosophila gastrulation: (I) mesodermal tube formation, (II) collapse of the mesoderm, (III) dorsal migration and spreading and (IV) monolayer formation. Our data provide evidence that these steps are temporally distinct and that each might require different chemical inputs. To support this, we analyzed the role of fibroblast growth factor (FGF) signaling, in particular the function of two Drosophila FGF ligands, Pyramus and Thisbe, during mesoderm migration. We determined that FGF signaling through both ligands controls movements in the radial direction. Thisbe is required for the initial collapse of the mesoderm onto the ectoderm, whereas both Pyramus and Thisbe are required for monolayer formation. In addition, we uncovered that the GTPase Rap1 regulates radial movement of cells and localization of the beta-integrin subunit, Myospheroid, which is also required for monolayer formation. Our analyses suggest that distinct signals influence particular movements, as we found that FGF signaling is involved in controlling collapse and monolayer formation but not dorsal movement, whereas integrins are required to support monolayer formation only and not earlier movements. Our work demonstrates that complex cell migration is not necessarily a fluid process, but suggests instead that different types of movements are directed by distinct inputs in a stepwise manner.
The effect of engine and transmission oil viscometrics on vehicle fuel consumption
Authors: Hawley J G , Bannister C D , Brace C J , Akehurst S , Pegg I , Avery M R
Published: June 2010

An extensive programme of work has been undertaken to assess the potential benefits of modulating the properties of both the engine and the transmission lubricating oils to achieve lower fuel consumption. The performance of the engine lubricants was evaluated on a production diesel engine on a transient test bed. The main engine lubricating-oil viscometric properties investigated were the cold cranking shear, the kinematic viscosity at 100°C, and the high-temperature high-shear value. Up to 3.5 per cent fuel economy improvement was observed over the New European Drive Cycle (NEDC), relative to current production lubricants. A model relating the fuel consumption to the oil properties was developed and verified using an experimental programme conducted on a chassis dynamometer.

In a related study, the effects of changes in the transmission lubricant properties were evaluated using a standard five-speed manual transmission fitted to a light-goods vehicle and tested on a chassis dynamometer. The lubricant was heated using an external energy source to simulate the effect of a more rapid warm-up; this reduced the viscosity of the lubricant and a fuel consumption improvement of 0.7 per cent was demonstrated over the NEDC from a 25°C start. In addition, a lower-viscosity lubricant blend was evaluated, which delivered a 1 per cent improvement in the fuel economy over the standard blend from a cold start, and a further 0.4 per cent improvement if heated.
Probing Bare High-Valent Transition Oxo–Metal Complexes: An Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Study of Reactive Intermediates
Authors: Chiavarino Barbara , Crestoni Maria Elisa , Fornarini Simonetta , Lanucara Francesco
Published: June 2010

Functional models of the Compound I intermediate of mono-oxygenase heme enzymes, namely [(TPFPP)•+FeIV=O]+ and [(TPFPP)MnV=O]+ (TPFPP = meso-tetrakis (pentafluorophenyl)porphyrinato dianion), are obtained as bare species by electrospray ionization from solutions of appropriate precursors and their reactivity is investigated in the gas-phase. By an alternative approach involving the reaction of a gaseous oxidant, the naked core of Compound I, [(PP–IX)•+FeIV=O]+ (PP–IX = protoporphyrin IX dianion) has been produced as well. This achievement, unprecedented in studies run in solution, is now made possible working in the gas-phase. The long lifetime ensured by the dilute gas-phase allows both structural details and elementary steps of the catalytic activity of these high-valent oxo–metal intermediates to be revealed. Depending on the features of the oxo–metal complex, ionic products are formed with neutral substrates involving: (i) addition, (ii) oxygen atom transfer and (iii) formal hydride transfer. In contrast, ionic products indicative of a net initial hydrogen atom transfer event are never observed. The reaction pathways of these ultimate catalytic intermediates, void of any trans axial ligand, counterion, solvent or protein environment, are thus elucidated.
Frontiers of Mass Spectrometry in Nucleic Acids Analysis
Authors: Oberacher Herbert
Published: June 2010

Nucleic acids research is a highly competitive field of research. A number of well established methods are available. The current output of high throughput (“next generation”) sequencing technologies is impressive, and still technologies are continuing to make progress regarding read lengths, bp per second, accuracy and costs. Although in the 1990s MS was considered as an analytical platform for sequencing, it was soon realized that MS will never be competitive. Thus, the focus shifted from de novo sequencing towards other areas of application where MS has proven to be a powerful analytical tool. Potential niches for the application of MS in nucleic acids research include genotyping of genetic markers (single nucleotide polymorphisms, short tandem repeats, and combinations thereof), quality control of synthetic oligonucleotides, metabolic profiling of therapeutics, characterization of modified nucleobases in deoxyribonucleic acid and ribonucleic acid molecules, and the study of non covalent interactions among nucleic acids as well as interactions of nucleic acids with drugs and proteins. The diversity of possible applications for MS highlights its significance for nucleic acid research.
Mass Spectrometric and Peptide Chip Epitope Analysis on the RA33 Autoantigen with Sera from Rheumatoid Arthritis Patients
Authors: El-Kased R.F. , Koy C. , Lorenz P. , Drynda S. , Guthke R. , Qian Z. , Koczan D. , Li Y. , Kekow J. , Thiesen H.-J. , Glocker M.O.
Published: June 2010

As the potential of epitope chips for routine application in diagnostics relies on the careful selection of peptides, reliable epitope mapping results are of utmost interest to the medical community. Mass spectrometric epitope mapping, in combination with peptide chip analysis, showed that autoantibodies from patients who suffered from rheumatoid arthritis (RA) were directed against distinct surface structures on the full-length human autoantigen RA33 as well as against partial sequences. Using the combined mass spectrometric epitope extraction and peptide chip analysis approach, four sequence motifs on RA33 emerged as immuno-positive, showing that epitopes were not randomly distributed on the entire RA33 amino acid sequence. A sequential epitope motif (245GYGGG249) was determined on the C-terminal part of RA33 which matched with the Western blot patient screening results using the full-length protein and, thus, was regarded as a disease-associated epitope. Other epitope motifs were found on N-terminal partial sequences (59RSRGFGF65, 111KKLFVG116) and again on the C-terminal part (266NQQPSNYG273) of RA33. As recognition of these latter three motifs was also recorded by peptide chip analysis using control samples which were negative in the Western blot screening, these latter motifs were regarded as “cryptic epitopes”. Knowledge of disease-associated epitopes is crucial for improving the design of a customized epitope peptide chip for RA and mass spectrometric epitope mapping pivotally assisted with selecting the most informative peptide(s) to be used for future diagnostic purposes.
Rapid Typing and Subtyping of Vaccine Strains of the Influenza Virus with High Resolution Mass Spectrometry
Authors: Schwahn Alexander B. , Wong Jason W.H. , Downard Kevin M.
Published: June 2010

The application of high-resolution mass spectrometry to type and subtype strains of the influenza virus within recent recommended vaccine formulations is described. Proteolytic digests of whole virus or separated hemagglutinin antigen generate conserved signature peptides of unique mass that can be used to characterise each component virus in a rapid and direct manner by the detection of their ions alone. The approach is demonstrated for two type A strains and one type B strain of human influenza viruses present in recommended seasonal vaccines in the northern and southern hemispheres from 2007 through 2010.
Perspectives and Retrospectives in Mass Spectrometry: One View
Authors: Cooks R. Graham , Ifa Demian R. , Sharma Gautam , Tadjimukhamedov Fatkhulla Kh. , Ouyang Zheng
Published: June 2010

Mass spectrometry benefits from a flexible definition which equates it with many aspects of the science of matter in the ionized state. The field continues to expand rapidly, not only to encompass larger and more complex molecules through more powerful instruments, but simultaneously towards in-situ measurements made using smaller, more flexible and just-sufficiently-powerful instruments. The senior author has been fortunate to work in mass spectrometry from 1967 to the present and has been involved in a wide range of efforts which have covered analytical, biological, organic, instrumental and physical aspects of the subject. This effort has been made in the company of a remarkable set of colleagues. From this vantage, it is possible to look both backwards and forwards in this prospective and retrospective piece. This presentation involves a personal look at places, people, instruments and concepts engaged in along a path through Mass Spectrometry. The journey goes from Natal, South Africa, via Cambridge, UK, through Kansas and on to Purdue University, in the great state of Indiana. It starts with natural products chemistry and moves to the physical chemistry of fragmentation and energy partitioning on to complex mixture analysis by tandem mass spectrometry and, hence, to the concepts of thermochemical determination by the kinetic method, preparation of materials by ion soft landing, the possible role of amino acid clusters in the origin of homochiral life and the elaboration of a set of ambient ionization methods for chemical analysis performed using samples in their native state. Special attention is given to novel concepts and instrumentation and to the emerging areas of ambient ionization, molecular imaging and miniature mass spectrometers. Personal mass spectrometers appear to be just over the horizon as is the large-scale use of mass spectrometry in field-based analysis, including point-of-care medical diagnostics.
The Gas-Phase Alcoholysis of Protonated Homoleptic Alkoxysilanes
Authors: Rainone Raquel , Malaspina Thaciana , Xavier Luciano A. , Riveros José M.
Published: June 2010

Tetra-alkoxysilanes are common and useful reagents in sol–gel processes and understanding their reactivity is important in the design of new materials. The mechanism of gas-phase reactions that mimic alcoholyis of Si(OMe)4 (usually known as TMOS) under acidic conditions have been studied by Fourier transform ion cyclotron resonance techniques and density functional calculations at the B3LYP/6-311+G(d,p) level. The proton affinity of TMOS has been estimated at 836.4 kJ mol−1 and protonation of TMOS gives rise to an ionic species that is best represented as trimethoxysilyl cations associated with a methanol molecule. Protonated TMOS undergoes rapid and sequential substitution of the methoxy groups in the gas-phase upon reaction with alcohols. The calculated energy profile of the reaction indicates that the substitution reaction through an SN2 type mechanism may be more favorable than frontal attack at silicon. Furthermore, the sequential substitution reactions are promoted by a mechanism that involves proton shuttle from the most favorable protonation site to the oxygen of the departing group mediated by the neutral reagent molecule.
Ion Microscopy with Resonant Ionization Mass Spectrometry: Time-of-Flight Depth Profiling with Improved Isotopic Precision
Authors: Pellin Michael J. , Veryovkin Igor V. , Levine Jonathan , Zinovev Alexander , Davis Andrew M. , Stephan Thomas , Tripa C. Emil , King Bruce V. , Savina Michael R.
Published: June 2010

There are four generally mutually exclusive requirements that plague many mass spectrometric measurements of trace constituents: (1) the small size (limited by the depth probed) of many interesting materials requires high useful yields to simply detect some trace elements, (2) the low concentrations of interesting elements require efficient discrimination from isobaric interferences, (3) it is often necessary to measure the depth distribution of elements with high surface and low bulk contributions, and (4) many applications require precise isotopic analysis. Resonant ionization mass spectrometry has made dramatic progress in addressing these difficulties over the past five years.
Anti-Poverty Policy for Families in the Next Century: From Welfare to Work—and Worries
Authors: Ellwood David T
Published: June 2010

This paper reveals that recent changes in social policy have included both sharp cutbacks in welfare for non-working families and dramatic increases in supports for low income working families. It explores the reasons for these changes, and documents how they have radically changed work incentives for some persons, notable single mothers. The result has been a large increase in work by low wage single parents. The paper concludes by examining several potential dangers of this new direction and explores the challenges that remain for the next century.
Economics in the Cyberclassroom
Authors: Navarro Peter
Published: June 2010

The coming of the cyberclassroom may change almost everything we do in teaching economics. This article discusses the size and scope of the cybereconomics market; the range and mix of instructional technologies; course design, development, and content; cyberinfrastructure and technical support; student characteristics, performance, and access; and labor issues. Some key findings include: the cybereconomics market is small but rapidly growing. Technical problems are common but can be minimized. It takes instructors significantly more time both to develop and teach a typical cybereconomics courses. Institutions, rather than instructors, are capturing a lion's share of the intellectual property rights.
Minority Groups in the Economics Profession
Authors: Collins Susan M
Published: June 2010

The primary objective of this paper is to provide information about minorities (blacks, Hispanics and Native Americans)in economics, at various stages in the education pipeline, and in the labor market. Despite sustained increases in the numbers and percentages of minorities earning bachelors degrees and Ph.D.s, the absolute numbers remain very small--only about 36 new Ph.D.s per year, including permanent residents. Minority economists are relatively underrepresented on four-year college faculties and in government employment. The paper also discusses activities by the AEA's committee on minority groups, aimed at increasing minority representation in the profession.
Keynesian Macroeconomics without the LM Curve
Authors: Romer David
Published: June 2010

Changes in both the macroeconomy and in macroeconomics suggest that the IS-LM-AS model is no longer the best baseline model of short-run fluctuations for teaching and policy analysis. This paper presents an alternative model that replaces the assumption that the central bank targets the money supply with an assumption that it follows a simple interest rate rule. The resulting model is simpler, more realistic, and more coherent than IS-LM-AS, not just in its treatment of monetary policy but in many other ways. The paper also discusses other alternatives to IS-LMAS.
Distinguished Lecture on Economics in Government—Fighting Poverty: Lessons from Recent U.S. History
Authors: Blank Rebecca M
Published: June 2010

Welfare reform efforts in the 1990s aimed at reducing welfare dependence and moving women into work. Public assistance use fell and labor force participation among mothers rose at a stunning rate over the decade. Poverty declined, but at a slower rate. These changes are causally related to the strong macroeconomy, welfare reform efforts, and other policy changes, especially the EITC and minimum wage expansions. This paper concludes that all of these effects reinforced each other, producing very large behavioral changes. It is too early to predict the effects of these changes on long-term family well-being.
Economic Analysis of Social Interactions
Authors: Manski Charles F
Published: June 2010

Economics is broadening its scope from analysis of markets to study of general social interactions. Developments in game theory, the economics of the family, and endogenous growth theory have led the way. Economists have also performed new empirical research using observational data on social interactions, but with much less to show. The fundamental problem is that observable outcomes may be generated by many different interaction processes, so empirical findings are open to a wide variety of interpretations. To make sustained progress, empirical research will need richer data, including experiments in controlled environments and subjective data on preferences and expectations.
Should America Save for its Old Age? Fiscal Policy, Population Aging, and National Saving
Authors: Elmendorf Douglas W , Sheiner Louise M
Published: June 2010

We examine whether the aging of the U.S. population adds force to traditional arguments for boosting national saving and conclude--perhaps surprisingly--that it may not. Aging boosts the demands on future resources, but it also changes the rate of return the U.S. economy can expect from saving. We find that the net effect on desired saving is small: some specifications imply that present consumption should fall by a fraction of 1 percent; others imply that consumption should actually increase. Thus, it is optimal to allow future cohorts to bear much/all of the burden of population aging.
Occupational Licensing
Authors: Kleiner Morris M
Published: June 2010

The study of the regulation of occupations has a long and distinguished tradition in economics. In this paper, I present the central arguments and unresolved issues involving the costs and benefits of occupational licensing. The main benefits that are suggested for occupational licensing involve improving quality for those persons receiving the service. In contrast, the costs attributed to this labor market institution are that it restricts the supply of labor to the occupation and thereby drives up the price of labor as well as of services rendered. Alternative public policies for this institution are identified.
An Economist's Guide to U.S. v. Microsoft
Authors: Gilbert Richard J , Katz Michael L
Published: June 2010

We analyze the central economic issues raised by U.S. v Microsoft. Network effects and economies of scale in applications programs created a barrier to entry for new operating system competitors, which the combination of Netscape Navigator and the Java programming language potentially could have lowered. Microsoft took actions to eliminate this threat to its operating system monopoly, and some of Microsoft's conduct very likely harmed consumers. While we recognize the risks of the government's proposed structural remedy of splitting Microsoft in two, we are pessimistic that a limited conduct remedy would be effective in this case.
Exclusivity and Tying in U.S. v. Microsoft: What We Know, and Don't Know
Authors: Whinston Michael D
Published: June 2010

Research on capital structure attempts to explain how corporations finance real investment, with particular emphasis on the proportions of debt vs. equity financing. There is no universal theory of the debt-equity choice, and no reason to expect one. But three useful conditional theories are reviewed in this paper. The tradeoff theory says that firms seek debt levels that balance the tax advantages of additional debt against the costs of possible financial distress. The pecking order theory says that the firm will borrow, rather than issuing equity, when internal cash flow is not sufficient to fund capital expenditures. Thus, the amount of debt will reflect the firm's cumulative need for external funds. The free cash flow theory says that dangerously high debt levels will increase value, despite the threat of financial distress. Each of these theories “works” for some firms in some circumstances. More general theories will require a deeper understanding of the financial objectives of corporate managers.
Institutional Economics: Then and Now
Authors: Rutherford Malcolm
Published: June 2010

This article gives a history of American institutionalism, and a brief comparison with the more recent “new” institutional economics. Institutionalism was a significant element in American economics between the Wars, but declined rapidly thereafter. The article outlines the movement's initial appeal, its contributions, and the reasons for its decline. Although the “new” institutionalism has few direct ties to the older tradition, some interesting commonalities are found and discussed. Links to the “new institutionalism” in sociology and political science, and to historical work on other “institutional” traditions are also mentioned.
A Theory of the Consumption Function, With and Without Liquidity Constraints
Authors: Carroll Christopher D
Published: June 2010

This paper argues that the modern stochastic consumption model, in which impatient consumers face uninsurable labor income risk, matches Milton Friedman's (1957) original description of the Permanent Income Hypothesis much better than the perfect foresight or certainty equivalent models did. The model can explain the high marginal propensity to consume, the high discount rate on future income, and the important role for precautionary behavior that were all part of Friedman's original framework. The paper also explains the relationship of these questions to the Euler equation literature, and argues that the effects of precautionary saving and liquidity constraints are often virtually indistinguishable.
Nonparametric Density and Regression Estimation
Authors: DiNardo John , Tobias Justin L
Published: June 2010

We provide a nontechnical review of recent nonparametric methods for estimating density and regression functions. The methods we describe make it possible for a researcher to estimate a regression function or density without having to specify in advance a particular--and hence potentially misspecified functional form. We compare these methods to more popular parametric alternatives (such as OLS), illustrate their use in several applications, and demonstrate their flexibility with actual data and generated-data experiments. We show that these methods are intuitive and easily implemented, and in the appropriate context may provide an attractive alternative to “simpler” parametric methods.
Fourier modal method for relief gratings with oblique boundary conditions
Authors: Gushchin Ivan , Tishchenko Alexandre V.
Published: June 2010

Oblique boundary conditions are introduced in the Fourier modal method at each slice of the staircase decomposition of an arbitrary profile of a dielectric corrugation grating. The precision and convergence improvement are demonstrated by comparison with reference methods.
Bayesian estimation of regularization and point spread function parameters for Wiener–Hunt deconvolution
Authors: Orieux François , Giovannelli Jean-François , Rodet Thomas
Published: June 2010

This paper tackles the problem of image deconvolution with joint estimation of point spread function (PSF) parameters and hyperparameters. Within a Bayesian framework, the solution is inferred via a globala posteriorilaw for unknown parameters and object. The estimate is chosen as the posterior mean, numerically calculated by means of a Monte Carlo Markov chain algorithm. The estimates are efficiently computed in the Fourier domain, and the effectiveness of the method is shown on simulated examples. Results show precise estimates for PSF parameters and hyperparameters as well as precise image estimates including restoration of high frequencies and spatial details, within a global and coherent approach.
Evidence for Epithelial-Mesenchymal Transition in Adult Human Pancreatic Exocrine Cells
Authors: Fanjul Marjorie , Gmyr Valéry , Sengenès Coralie , Ratovo Ginette , Dufresne Marlène , Lefebvre Bruno , Kerr-Conte Julie , Hollande Etienne
Published: June 2010

It has been shown that adult pancreatic ductal cells can dedifferentiate and act as pancreatic progenitors. Dedifferentiation of epithelial cells is often associated with the epithelial-mesenchymal transition (EMT). In this study, we investigated the occurrence of EMT in adult human exocrine pancreatic cells both in vitro and in vivo. Cells of exocrine fraction isolated from the pancreas of brain-dead donors were first cultured in suspension for eight days. This led to the formation of spheroids, composed of a principal population of cells with duct-like phenotype. When cultivated in tissue culture-treated flasks, spheroid cells exhibited a proliferative capacity and coexpressed epithelial (cytokeratin7 and cytokeratin19) and mesenchymal (vimentin and α-smooth muscle actin) markers as well as marker of progenitor pancreatic cells (pancreatic duodenal homeobox factor-1) and surface markers of mesenchymal stem cells. The switch from E-cadherin to N-cadherin associated with Snail1 expression suggested that these cells underwent EMT. In addition, we showed co-expression of epithelial and mesenchymal markers in ductal cells of one normal adult pancreas and three type 2 diabetic pancreases. Some of the vimentin-positive cells were found to coexpress glucagon or amylase. These results point to the occurrence of EMT, which may take place on dedifferentiation of ductal cells during the regeneration or renewal of human pancreatic tissues.
A potent antitumor polysaccharide from the edible brown seaweedHydroclathrus clathratus
Authors: Wang Hui , Chiu Lawrence C.M. , Ooi Vincent E.C. , Ang Put O.
Published: June 2010

A sulfated polysaccharide H3-a1 [designated polysaccharide fraction, H3-a1, ofHydroclathrus clathratus(HCP)] was isolated and purified from an edible brown seaweedHydroclathrus clathratus; HCP contained about 8.6% protein and a relatively high sulfur content (8.2%). HCP significantly affected the growth of human acute promyelocytic leukemia cells (HL-60), human breast carcinoma (MCF-7) and human hepatocellular carcinoma cancer cell lines. As revealed by flow cytometry, when HCP was co-incubated with HL-60 and MCF-7 cells for 72 h, it induced significant sub-G1 arrest (apoptosis) of these cells. HCP caused G1 phase arrest but did not induce terminal differentiation of these cancer cells.In vivoantitumor tests showed that HCP inhibited tumor growth at doses of 20 and 50 mg kg-1in tumor-bearing BALB/c (supplied by the Laboratory Animal Services Centre of The Chinese University of Hong Kong) mice, but this effect was not due to anin vivoinhibitory effect on tumorigenesis. Nevertheless, HCP suppressed ascitic Sarcoma 180 tumor growth and prolonged the life span of the tumor-bearing mice by about 30–40%. HCP had no observed toxic side effects; it did not affect blood cells, or body, liver or spleen weights of mice 4, 7 and 10 days after treatment. This sulfated polysaccharide induced increased tumor necrosis factor-alpha (TNF-α) level in mouse serum. It also activated peritoneal macrophages to secrete TNF-α and nitric oxide.
Residual Strain Effects on Bridging Stress of Cracked and Delaminated Fiber Metal Laminates
Authors: Wang John T. , Smith Stephen W.
Published: June 2010

An analytical model is developed that accounts for the effects of both residual thermal strain and residual post-cure stretching strain in the prediction of the bridging stress and the crack opening displacement (COD) of cracked and delaminated fiber metal laminates. Two GLARE® tensile specimen configurations with center cracks in the aluminum layers, one with elliptically shaped delaminations and the other with rhomboidally shaped delaminations, are analyzed with the governing solutions of the analytical model. The shear deformations at the delamination front of either the resin rich region at the metal-fiber layer interface or the fiber layer itself are modeled. Analytical results show that the presence of residual thermal strain reduces the bridging stress while residual post-cure stretching strain increases the bridging stress. A high post-cure stretching level, inducing a greater bridging stress for lowering the COD and also affecting crack closure at crack tips, can result in an increased fatigue life. The use of either of the two shear models has negligible effect on the calculated bridging stress and COD. The analytical results are correlated with available test data of CODs for validating the analytical model.
Viennese Moderne and Its Spatial Planes, Sounded
Authors: Dolp Laura
Published: June 2010

The opening of Mahler's “Der Abschied” from Das Lied von der Erde demonstrates a special set of musical conditions that include spare textures, a wide disposition of instrumental forces, and the effect of temporal suspension. This transparency allows the process of individuation and exchange between musical elements to come to the fore, especially in relation to timbre. Through this passage Mahler highlights voices that work in synthesis with those that are juxtaposed. The first half of the study explores how this music is defined spatially through this process. It then proposes that this space is historically meaningful because Mahler's construction of musical space is analogous to the visual tensions in the landscape works of his artistic contemporaries Gustav Klimt and Egon Schiele. In both musical and visual context, these tensions reflect the diversity of the Viennese Moderne through their ephemeral and laconic qualities.

Mahler's compositional tendency to “suspend” time and flatten the sonic plane gave his critics fodder for an ideological argument that involved ornamentation versus organic development, since his methods reflected ambiguously on the nineteenthcentury tradition of teleologically based symphonic forms. “Abschied” derived its relevancy from neither static surface nor motivic development but by its capacity to suggest unique spatial relationships. The movement initiates a timbrally and rhythmically nuanced recitative, in the form of subtle decays and articulated renewals. Like Klimt's superimposed visual planes, which create a synthetic relationship between figure and ground, Mahler's music suggests incremental distances between subjects. The economy of his music relates also to Schiele's laconic subjects. In Mahler's landscapes, both types of experiments coexist.
Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia
Authors: Occhi G , Trivellin G , Ceccato F , De Lazzari P , Giorgi G , Demattè S , Grimaldi F , Castello R , Davì M V , Arnaldi G , Salviati L , Opocher G , Mantero F , Scaroni C
Published: June 2010

Background

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27KIP1 encoding gene CDKN1B have been associated with two well-defined hereditary conditions, familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 4 (MEN4). Somatotropinomas are present in most AIP mutated FIPA kindreds, as well as in two-thirds of MEN4 patients who carry pituitary tumors.

Methods

Germline DNA samples of 131 Italian sporadic acromegalic patients including 38 individuals with multiple tumors, and of six FIPA families (four homogeneous for prolactinomas and two heterogeneous with prolactin/nonfunctioning pituitary adenomas) were collected in a multicentric collaborative study. The prevalence of AIP and CDKN1B gene point mutations and copy number variations were evaluated.

Results

Two novel (IVS3+1G>A and c.871G>A) and one previously described (c.911G>A) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49±18, range 30–67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871G>A substitution was detected in a patient who also carried a MEN1 mutation suggesting that she is a double heterozygote. The possible pathogenic effect on AIP splicing of the silent substitution c.144G>A found in another patient was ruled out using a minigene-based approach. CDKN1B mutations/rearrangements were neither identified in patients with multiple neoplasia nor in FIPA families.

Conclusion

AIP is mutated in about 3% of apparently sporadic acromegalic patients. The relatively high age at diagnosis, as well as its sporadic presentation, suggests that these patients are carriers of mutations with reduced pathogenicity. p27KIP1 is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.