bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons from History: Why Race and Ethnicity Have Played a Major Role in Biomedical Research
Authors: Duster Troy 
Published: September 2006

Perhaps it has always been so, but certainly in the post-Enlightenment era there are inevitable linkages between the fields of law, medicine, and science. Each of these realms of activity is embedded in the social milieu of the era, with practitioners emerging from families, communities, regions, and nations bearing deep unexamined assumptions about what is natural and normal. Equally important, these fields’ theoretical accounts of natural behavior will tend to dovetail and fit each other's – most especially as they pertain to the grand social issues of the period.For the last century and a half, a conversation with a cross-section of lawyers, scientists, and physicians at any given historical juncture would produce a remarkable pattern, consistently repeated: There would be strong enthusiasm for the idea that the “current state of knowledge and practice” is both objective and transcends the current social milieu.
The Use of Race and Ethnicity in Medicine: Lessons from the African-American Heart Failure Trial
Authors: Cohn Jay N. 
Published: September 2006

The practice of using race or ethnic origin as a distinguishing feature of populations or individuals seeking health care is a universal and well-accepted custom in medicine. Although the origin of this practice may, in part, reflect past prejudicial attitudes, its use today can certainly be defended as a useful means of improving diagnostic and therapeutic efforts. Indeed, the tradition of dividing populations by some racial distinction in clinical research has nearly always revealed differences in mechanisms of disease and disease frequency that can enhance diagnostic and therapeutic precision.At the conference occasioning this symposium, Professors Duster and Rotimi provided persuasive evidence that so-called race is not an accurate way to distinguish populations and that identification by race has led to serious prejudice. Professor Cho pleaded that race should never be used to characterize population differences.
The Devil's Choice: Re-Thinking Law, Ethics, and Symptom Relief in Palliative Care
Authors: Magnusson Roger S. 
Published: September 2006

In 1982, cinemas around the world screened Sophie's Choice, a film starring Meryl Streep and Kevin Kline, adapted from the book by William Styron. The film opens with Stingo, a young journalist from the South, who arrives in New York in 1947 and rents a room in Brooklyn. Stingo is drawn into a relationship with Sophie and Nathan, the couple who live upstairs. Sophie is a Polish concentration camp survivor; Nathan is the man who saved her when she arrived in America. Nathan is charismatic, schizophrenic, and violent.In one of the film's flashbacks, a German soldier imposes a terrible choice on Sophie, a young mother who arrives at Auschwitz with other prisoners from Krakow. Sophie is ordered to choose which of her two children will be sent to the ovens, and which will live.
The Limits of Disclosure: What Research Subjects Want to Know about Investigator Financial Interests
Authors: Grady Christine , Horstmann Elizabeth , Sussman Jeffrey S. , Hull Sara Chandros 
Published: September 2006

Concerns about the influence of financial interests on research have increased, along with research dollars from pharmaceutical and other for-profit companies. Researchers’ financial ties to industry sponsors of research have also increased. Financial interests in biomedical research could influence research design, conduct, or reporting, and could compromise data integrity, participant safety, or both. Investigators’ financial ties with for-profit companies may influence reported scientific results, and may have compromised research participant safety.Disclosure is one commonly accepted method of managing financial relationships in order to minimize possible threats to scientific objectivity, the safety of research participants, or public trust in the integrity of clinical research. Disclosure is presumed useful to the extent that “it gives those who would be affected, or who are otherwise in a good position to assess the risks, information they need to make their own decision.”
The Ethical Health Lawyer
Authors: Schwartz Robert 
Published: September 2006

What happens when being a good doctor requires being a bad citizen? What should a doctor do when living up to the requirements of a professional code of ethics or staying true to deeply held personal values requires breaking the law? What should a health care professional do when the appropriate conduct in a particular case is inconsistent with a more generalized principle that has been incorporated into law? Further, what is the role of the ethical health lawyer who advises a health care provider facing such a dilemma?As health care lawyers advising individuals and institutions, is it our job to advise our clients of all the options available to them, and all the potential legal consequences, or is our role simply to keep our clients acting within the law? Are we information providers, policy counselors, risk managers, or some combination of these?
The need for a clinical ethics service and its goals in a community healthcare service centre: a survey
Authors: Racine E , Hayes K 
Published: September 2006

Objectives:To (1) assess whether according to healthcare providers, the creation of an ethics service responds to a need; (2) assess the importance of an ethics service for healthcare providers; (3) determine what ethics services should be offered and the preferred formats of delivery; and (4) identify key issues to be initially dealt with by the ethics service.Design:A survey of healthcare providers in Québec’s Centre Local de Services Communautaires (CLSC), healthcare institutions dedicated to community health and social services.Findings:96 (95%) respondents agreed that an ethics service was needed, and on average the ethics service project was judged to be very important. Preferred formats for ethics consultation and education were identified, as well as key concerns such as the need of respect for the patient as a person, elder abuse and ethical issues in home care.Conclusion:This survey is helping in the implementation of an ethics service and can guide others in similar healthcare institutions.
A taxonomic revision of Helichrysum sect. Stoechadina (Asteraceae, Gnaphalieae)
Authors: Galbany-Casals Mercè , Sáez Llorenç , Benedí Carles 
Published: September 2006

A taxonomic revision of Helichrysum sect. Stoechadina, a section with a Mediterranean distribution, is presented. Taxonomic, nomenclatural, morphological, chromosomal, geographical, and ecological data are provided for each taxon. Eleven taxa are recognized, two lectotypifications are proposed, and a taxonomic key and a sectional description are included. The following new combinations are proposed: Helichrysum italicum subsp. siculum (Jord. & Fourr.) Galbany, L. Sáez & Benedí comb. nov. and Helichrysum italicum subsp. picardii (Boiss. & Reut.) Galbany, L. Sáez & Benedí comb. nov.
Transcranial Doppler Monitoring of Transcervical Carotid Stenting With Flow Reversal Protection
Authors: Ribo Marc , Molina Carlos A. , Alvarez Beatriz , Rubiera Marta , Alvarez-Sabin Jose , Matas Manel 
Published: September 2006

Background and Purpose—Transfemoral carotid stenting, despite becoming very frequent, has some limitations such as difficult groin access in few patients, lack of distal protection during filter placement, or embolization despite protection. Transcervical stenting (TCS) is a novel technique during which a common carotid to jugular vein shunt is placed creating a protective reversal flow in the internal carotid artery after proximal common carotid artery (CCA) clamping. We aim to study, with transcranial Doppler (TCD), cerebral flow changes and microemboli detection during transcervical stenting.Methods—From September 2005 to March 2006, of 65 consecutive patients eligible for carotid revascularization, 23 were considered high risk (sapphire criteria) and underwent TCS. Neurologic examination was performed before and after the procedure by a neurologist and a preprocedure vascular reactivity TCD examination was done in all patients.Results—After CCA clamping, flow inversion was observed in the anterior cerebral artery, supplying blood to the middle cerebral artery (MCA) and internal carotid artery (reversal). TCD did not detect any air/solid emboli during stent deployment and angioplasty confirming the reversal flow protection hypothesis. Mean reversal flow time was 15.4 minutes; in all cases, substantial MCA flow was present during CCA clamping (initial mean velocity 30 cm/s), and a slow gradual increase was observed traducing collateral flow recruitment (mean velocity after 5 minutes 36 cm/s,P<0.001). Flow increase was observed in all patients except in those with preprocedural exhausted ipsilateral vascular reactivity (16% versus 2%,P=0.036). The only in-procedure complication was one transient ischemic attack. After CCA unclamping, normal antegrade flow was restored in anterior cerebral artery and mean final MCA velocity increased 16% according to preprocedure flow.Conclusions—TCS with protective internal carotid artery flow reversal can eliminate showers of micoremboli during stent deployment making it a promising carotid revascularization technique in high-risk patients with carotid stenosis.
Three-Dimensional Structure and Dynamics of African Easterly Waves. Part II: Dynamical Modes
Authors: Hall Nicholas M. J. , Kiladis George N. , Thorncroft Chris D. 
Published: September 2006

Abstract
A primitive equation model is used to study the linear normal modes of the African easterly jet (AEJ). Reanalysis data from the summertime mean (June–September; JJAS) flow is used to provide zonally uniform and wavy basic states. The structure and growth rates of modes that grow over West Africa on these basic states are analyzed. For zonally uniform basic states, the modes resemble African easterly waves (AEWs) as in many previous studies, but they are quite baroclinic and surface intensified.
For wavy basic states the modes have a longitudinal structure determined by the AEJ. They have a surface-intensified baroclinic structure upstream and a deep barotropic structure downstream, as confirmed by energy conversion diagnostics. These modes look remarkably similar to the composite easterly wave structures found by the authors in a companion paper. The similarity extends to the phase relationship of vertical velocity with streamfunction, which resembles OLR composites, suggesting a dynamical influence on convection.
Without damping, the mode for the wavy basic state has a growth rate of 0.253 day−1. With a reasonable amount of low-level damping this mode is neutralized. It has a period of 5.5 days and a wavelength of about 3500 km. Further results with monthly mean basic states show slight variations, as the wave packet essentially follows displacements of the jet core. Experiments focused on specific active and passive years for easterly waves (1988 and 1990) do not yield significantly different results for the modes. These results, and in particular, the stability of the system, lead to the conclusion that barotropic–baroclinic instability alone cannot explain the initiation and intermittence of AEWs, and a finite-amplitude initial perturbation is required.
Dynamic Adjustment in a Numerically Simulated Mesoscale Convective System: Impact of the Velocity Field
Authors: Nascimento Ernanide Lima , Droegemeier Kelvin K. 
Published: September 2006

Abstract
An identical twin methodology is applied to a three-dimensional cloud model to study the dynamics of adjustment in deep convective storms. The principal goal is to diagnose how mass and velocity fields mutually adjust in order to better understand the relative information content (value) of observations, the physical interdependency among variables, and to help in the design of dynamically consistent analyses to ensure smooth startup of numerical prediction models.
Using a control simulation (“truth” or “nature” run) of an idealized long-lived bow echo convective system, a series of adjustment experiments is created by resetting, in various combinations, the horizontal and vertical velocity components of the control run to their undisturbed base state values during the mature stage of storm system evolution. The integrations then are continued for comparison against the control. This strategy represents a methodology for studying transient response to an impulsive perturbation in a manner conceptually similar to that used in geostrophic and hydrostatic adjustment.
The results indicate that resetting both horizontal velocity components alters the character of the convection and slows considerably the overall storm system evolution. In sharp contrast, when only the vertical velocity component is reset, the model quickly restores both updrafts and downdrafts to nearly their correct (control run) values, producing subsequent storm evolution virtually identical to that of the control run. Other combinations yield results in between these two extremes, with the cross-line velocity component proving to be most important in restoration toward the control run. This behavior is explained by acoustic adjustment of the pressure and velocity fields in direct response to changes in velocity divergence forced by the withdrawal of wind information.
The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration
Authors: Rossi Lara , Manfredini Rossella , Bertolini Francesco , Ferrari Davide , Fogli Miriam , Zini Roberta , Salati Simona , Salvestrini Valentina , Gulinelli Sara , Adinolfi Elena , Ferrari Sergio , Di Virgilio Francesco , Baccarani Michele , Lemoli Roberto M. 
Published: September 2006

AbstractHoming and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and nonpeptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation by migrating CD34+ cells, and increased cell adhesion to fibronectin. In vivo, preincubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (Gαi) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP- and CXCL12-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5′-triphosphatase (GTPase) Rac2 and downstream effectors Rho GTPase–activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the homing of HSCs to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving Gαi proteins and RhoGTPases.
Promoter SNPs in G1/S checkpoint regulators and their impact on the susceptibility to childhood leukemia
Authors: Healy Jasmine , Bélanger Hélène , Beaulieu Patrick , Larivière Mathieu , Labuda Damian , Sinnett Daniel 
Published: September 2006

AbstractMutations leading to the alteration of cell-cycle checkpoint functions are a common feature of most cancers. Because of the highly regulated nature of the cell cycle, it seems likely that variation in gene dosage of key components due to functional regulatory polymorphisms could play an important role in cancer development. Here we provide evidence of the involvement of promoter single-nucleotide polymorphisms (pSNPs) in the cyclin-dependent–kinase inhibitor genes CDKN2A, CDKN2B, CDKN1A, and CDKN1B in the etiology of childhood pre-B acute lymphoblastic leukemia (ALL). A case-control study, conducted in 240 patients with pre-B ALL and 277 healthy controls, combined with a family-based analysis using 135 parental trios, all of French-Canadian origin, were used to evaluate single-site genotypic as well as multilocus haplotypic associations for a total of 10 pSNPs. Using both study designs, we showed evidence of association between variants CDKN2A −222A, CDKN2B −593A, and CDKN1B −1608A, and an increased risk of ALL. These findings suggest that variable expression levels of cell-cycle inhibitor genes CDKN2A, CDKN2B, and CDKN1B due to regulatory polymorphisms could indeed influence the risk of childhood pre-B ALL and contribute to carcinogenesis.
PDGFRα-expressing mesenchyme regulates thymus growth and the availability of intrathymic niches
Authors: Jenkinson William E. , Rossi Simona W. , Parnell Sonia M. , Jenkinson Eric J. , Anderson Graham 
Published: September 2006

AbstractThe thymus provides a specialized site for the production of T cells capable of recognizing foreign antigens in the context of self–major histocompatibility complex (MHC) molecules. During development, the thymus arises from an epithelial rudiment containing bipotent progenitors that differentiate into distinct cortical and medullary epithelial cells to regulate the maturation and selection of self-tolerant CD4+ and CD8+ T cells. In addition to their differentiation, thymic epithelial cells undergo cellular expansion to ensure that sufficient intrathymic cellular niches are available to support the large number of immature thymocytes required to form a self-tolerant T-cell pool. Thus, intrathymic T-cell production is intimately linked to the formation and availability of niches within thymic microenvironments. Here, we show the increase in intrathymic niches caused by the proliferation of the epithelium in the developing thymus is temporally regulated, and correlates with the presence of a population of fetal thymic mesenchyme defined by platelet-derived growth factor receptor α (PDGFRα) expression. Depletion of PDGFRα+ mesenchyme from embryonic thymi prior to their transplantation to ectopic sites results in the formation of functional yet hypoplastic thymic tissue. In summary, we highlight a specialized role for PDGFRα+ fetal mesenchyme in the thymus by determining availability of thymic niches through the regulation of thymic epithelial proliferation.
Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation
Authors: Mullally Ann , Ritz Jerome 
Published: September 2006

AbstractThe last 2 years have seen much excitement in the field of genetics with the identification of a formerly unappreciated level of “structural variation” within the normal human genome. Genetic structural variants include deletions, duplications, and inversions in addition to the recently discovered, copy number variants. Single nucleotide polymorphisms are the most extensively evaluated variant within the genome to date. Combining our knowledge from these studies with our rapidly accumulating understanding of structural variants, it is apparent that the extent of genetic dissimilarity between any 2 individuals is considerable and much greater than that which was previously recognized. Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. With advances in DNA sequencing technology we now have the capacity to perform genome-wide analysis in a high throughput fashion, permitting a detailed genetic analysis of patient and donor prior to transplantation. Understanding the significance of this additional genetic information and applying it in a clinically meaningful way will be one of the challenges faced by transplant clinicians in the future.
Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features
Authors: Falini Brunangelo , Nicoletti Ildo , Martelli Massimo F. , Mecucci Cristina 
Published: September 2006

AbstractThe nucleophosmin (NPM1) gene encodes for a multifunctional nucleocytoplasmic shuttling protein that is localized mainly in the nucleolus. NPM1 mutations occur in 50% to 60% of adult acute myeloid leukemia with normal karyotype (AML-NK) and generate NPM mutants that localize aberrantly in the leukemic-cell cytoplasm, hence the term NPM-cytoplasmic positive (NPMc+ AML). Cytoplasmic NPM accumulation is caused by the concerted action of 2 alterations at mutant C-terminus, that is, changes of tryptophan(s) 288 and 290 (or only 290) and creation of an additional nuclear export signal (NES) motif. NPMc+ AML shows increased frequency in adults and females, wide morphologic spectrum, multilineage involvement, high frequency of FLT3-ITD, CD34 negativity, and a distinct gene-expression profile. Analysis of mutated NPM has important clinical and pathologic applications. Immunohistochemical detection of cytoplasmic NPM predicts NPM1 mutations and helps rationalize cytogenetic/molecular studies in AML. NPM1 mutations in absence of FLT3-ITD identify a prognostically favorable subgroup in the heterogeneous AML-NK category. Due to their frequency and stability, NPM1 mutations may become a new tool for monitoring minimal residual disease in AML-NK. Future studies should focus on clarifying how NPM mutants promote leukemia, integrating NPMc+ AML in the upcoming World Health Organization leukemia classification, and eventually developing specific antileukemic drugs.
The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis
Authors: Dispenzieri Angela , Lacy Martha Q. , Zeldenrust Steven R. , Hayman Suzanne R. , Kumar Shaji K. , Geyer Susan M. , Lust John A. , Allred Jacob B. , Witzig Thomas E. , Rajkumar S. Vincent , Greipp Philip R. , Russell Stephen J. , Kabat Brian , Gertz Morie A. 
Published: September 2006

AbstractPrimary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, is highly active in patients with multiple myeloma. We studied the toxicity and efficacy of lenalidomide in patients with AL. Patients with symptomatic AL, a measurable plasma cell disorder, and adequate hematologic and renal reserve were eligible. Patients received single-agent lenalidomide. If there was no evidence of progression after 3 months or of hematologic response after 3 cycles, dexamethasone was added. Twenty-three patients were enrolled. Thirteen were previously treated. Organ involvement was cardiac (64%), renal (73%), hepatic (23%), and nerve (14%). Within the first 3 cycles of therapy, 10 patients discontinued treatment: 4 early deaths, 3 adverse events, and 3 other causes. With a median follow-up of 17 months, 10 patients responded to treatment. In these patients, responses included 9 hematologic, 4 renal, 2 cardiac, and 2 hepatic. All but one of the responders had dexamethasone added to their treatment program. The most common grade 3 or 4 adverse events at least possibly attributable to lenalidomide were neutropenia (45%), thrombocytopenia (27%), rash (18%), and fatigue (18%). In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation.