bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital versus Print: Energy Performance in the Selection and Use of Scholarly Journals
Authors: Gard David L. , Keoleian Gregory A. 
Published: March 2003

SummaryAdvances in digital technology and the growth of information networks are revolutionizing human activity. The Internet has been championed as a new tool for environmental improvement. A life‐cycle energy analysis of digital libraries, a growing application of information technology, was conducted to test this premise.Life‐cycle models were compared for journal collections in digital and traditional formats. The basis for analysis was the amount of information in a typical scientific journal article (∼12 pages), which is equivalent to 0.97 hr of on‐screen reading time. Digital system elements such as servers, routers, laser printers, and computer workstations were modeled. Journal production, delivery, storage, binding, interlibrary loan, and photocopying were examined for the traditional system. Building‐related infrastructure, office paper, and personal transportation of the library patron were analyzed for both cases. In all, the study incorporated nearly 30 model elements, 90 input variables, and numerous fixed parameters.Five primary scenarios were constructed to consider increasing levels of complexity. Scenario 1 assumes only one reading per article (unit of analysis). Additional scenarios assume 1,000 readings and vary the following: laser printing, photocopying, and personal transportation. Energy consumed by the digital collection ranged between 4.10 and 216 MJ. The traditional system realized burdens from 0.55 to 525 MJ. Four significant effects were uncovered: (1) Energy consumption per unit was highly influenced by the number of readings per article. (2) Networking infrastructure by itself had a relatively small effect on total energy consumed by the digital system. (3) When personal transportation was considered, its effects tended to dominate. (4) The impact of making personal copies varied. Photocopying always increased energy consumption, whereas laser printing actually saved energy when it substituted for on‐screen reading.
Human NK cell development in NOD/SCID mice receiving grafts of cord blood CD34+ cells
Authors: Kalberer Christian P. , Siegler Uwe , Wodnar-Filipowicz Aleksandra 
Published: March 2003

AbstractDefinition of the cytokine environment, which regulates the maturation of human natural killer (NK) cells, has been largely based on in vitro assays because of the lack of suitable animal models. Here we describe conditions leading to the development of human NK cells in NOD/SCID mice receiving grafts of hematopoietic CD34+ precursor cells from cord blood. After 1-week-long in vivo treatment with various combinations of interleukin (IL)–15, flt3 ligand, stem cell factor, IL-2, IL-12, and megakaryocyte growth and differentiation factor, CD56+CD3- cells were detected in bone marrow (BM), spleen, and peripheral blood (PB), comprising 5% to 15% of human CD45+ cells. Human NK cells of NOD/SCID mouse origin closely resembled NK cells from human PB with respect to phenotypic characteristics, interferon (IFN)–γ production, and cytotoxicity against HLA class 1–deficient K562 targets in vitro and antitumor activity against K562 erythroleukemia in vivo. In the absence of growth factor treatment, CD56+ cells were present only at background levels, but CD34+CD7+ and CD34-CD7+ lymphoid precursors with NK cell differentiation potential were detected in BM and spleen of chimeric NOD/SCID mice for up to 5 months after transplantation. Our results demonstrate that limitations in human NK cell development in the murine microenvironment can be overcome by treatment with NK cell growth–promoting human cytokines, resulting in the maturation of IFN-γ–producing cytotoxic NK cells. These studies establish conditions to explore human NK cell development and function in vivo in the NOD/SCID mouse model. (Blood. 2003;102:127-135)
Reovirus oncolysis as a novel purging strategy for autologous stem cell transplantation
Authors: Thirukkumaran Chandini M. , Luider Joanne M. , Stewart Douglas A. , Cheng Tina , Lupichuk Sasha M. , Nodwell Michael J. , Russell James A. , Auer Iwona A. , Morris Donald G. 
Published: March 2003

AbstractHematologic stem cell rescue after high-dose cytotoxic therapy is extensively used for the treatment of many hematopoietic and solid cancers. Gene marking studies suggest that occult tumor cells within the autograft may contribute to clinical relapse. To date purging of autografts contaminated with cancer cells has been unsuccessful. The selective oncolytic property of reovirus against myriad malignant histologies in in vitro, in vivo, and ex vivo systems has been previously demonstrated. In the present study we have shown that reovirus can successfully purge cancer cells within autografts. Human monocytic and myeloma cell lines as well as enriched ex vivo lymphoma, myeloma, and Waldenström macroglobulinemia patient tumor specimens were used in an experimental purging model. Viability of the cell lines or purified ex vivo tumor cells of diffuse large B-cell lymphoma, chronic lymphocytic leukemia, Waldenström macroglobulinemia, and small lymphocytic lymphoma was significantly reduced after reovirus treatment. Further, [35S]-methionine labeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of cellular proteins demonstrated reovirus protein synthesis and disruption of host cell protein synthesis as early as 24 hours. Admixtures of apheresis product with the abovementioned tumor cells and cell lines treated with reovirus showed complete purging of disease. In contrast, reovirus purging of enriched ex vivo multiple myeloma, Burkitt lymphoma, and follicular lymphoma was incomplete. The oncolytic action of reovirus did not affect CD34+ stem cells or their long-term colony-forming assays even after granulocyte colony-stimulating factor (G-CSF) stimulation. Our results indicate the ex vivo use of an unattenuated oncolytic virus as an attractive purging strategy for autologous stem cell transplantations. (Blood. 2003;102:377-387)
The proteasome inhibitor PS-341 sensitizes neoplastic cells to TRAIL-mediated apoptosis by reducing levels of c-FLIP
Authors: Sayers Thomas J. , Brooks Alan D. , Koh Crystal Y. , Ma Weihong , Seki Naoko , Raziuddin Arati , Blazar Bruce R. , Zhang Xia , Elliott Peter J. , Murphy William J. 
Published: March 2003

AbstractBecause of the pivotal role the proteasome plays in apoptosis, inhibitors of this enzyme, such as PS-341, provide a great opportunity for exploring synergy between proteasome inhibition and other apoptosis-inducing agents. Tumor necrosis factor—related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. In overnight assays, combinations of PS-341 and TRAIL were much more effective than either agent alone in promoting apoptosis of a murine myeloid leukemia, C1498, and a murine renal cancer, Renca. For C1498 cells, apoptosis sensitization by PS-341 affected neither the activity of nuclear factor κB (NF-κB) nor the levels of most antiapoptotic proteins. However, reductions in the antiapoptotic protein c-FLIP in response to PS-341 were observed in both C1498 and Renca cells. Treatment of normal bone marrow mixed with C1498 tumor cells for 18 hours with a combination of PS-341 and TRAIL resulted in a specific depletion of the tumor cells. Upon transfer to irradiated syngeneic recipient mice, mixtures treated with the PS-341 plus TRAIL combination resulted in enhanced long-term tumor-free survival of mice. These data therefore support the targeting of apoptotic pathways in tumor cells, using combinations of agents such as PS-341 and TRAIL that interact synergistically to preferentially promote tumor cell apoptosis. (Blood. 2003;102:303-310)
Ser727/Tyr701-phosphorylated Stat1 is required for the regulation of c-Myc, cyclins, and p27Kip1 associated with ATRA-induced G0/G1 arrest of U-937 cells
Authors: Dimberg Anna , Karlberg Inger , Nilsson Kenneth , Öberg Fredrik 
Published: March 2003

AbstractAll-trans retinoic acid (ATRA)—induced growth arrest of myeloid cells is associated with a sequential regulation of cyclins and cyclin-dependent kinase inhibitors (CKIs), which modulates the cell cycle machinery and inhibits the G1-S phase progression. ATRA treatment of myeloid cells induces up-regulation and tyrosine phosphorylation of Stat1, a member of the STAT (signal transducer and activator of transcription) transcription factor family that has been implicated in growth arrest in response to interferons. We have previously shown that ATRA-induced cell cycle arrest is dependent on tyrosinephosphorylated Stat1. In this study, we show that there is a basal level of Stat1 Ser727 phosphorylation in U-937 cells, which is transiently increased in response to ATRA treatment. Using Stat1Ser727Ala-expressing sublines, we provide evidence that Ser727 phosphorylation of Stat1 is required for ATRA-induced growth arrest. To shed further light on the role of Stat1 in ATRA-induced cell cycle arrest, cyclin and CKI expression was analyzed during ATRA treatment in U-937 sublines expressing Stat1Ser727Ala and Stat1Tyr701Phe. Our results show that Ser727/Tyr701-phosphorylated Stat1 plays a key role as a prerequisite for the ATRA-induced down-regulation of c-Myc; cyclins A, B, D2, D3, and E; and the simultaneous up-regulation of p27Kip1, associated with arrest in the G0/G1 phase of the cell cycle. (Blood. 2003;102:254-261)
GMCSF activates NF-κB via direct interaction of the GMCSF receptor with IκB kinase β
Authors: Ebner Karin , Bandion Alexander , Binder Bernd R. , de Martin Rainer , Schmid Johannes A. 
Published: March 2003

Abstract
Granulocyte-macrophage colony-stimulating factor (GMCSF) has a central role in proliferation and differentiation of hematopoetic cells. Furthermore, it influences the proliferation and migration of endothelial cells. GMCSF elicits these functions by activating a receptor consisting of a ligand-specific α-chain and a β-chain, which is common for GMCSF, interleukin-3 (IL-3), and IL-5. It is known that various signaling molecules such as Janus kinase 2 or transcription factors of the signal transducer and activator of transcription (STAT) family bind to the common β-chain and initiate signaling cascades. However, α-chain—specific signal transduction adapters have to be postulated given that IL-3, IL-5, and GMCSF induce partly distinct biologic responses. Using a yeast 2-hybrid system, we identified the α-chain of the GMCSF receptor (GMRα) as putative interaction partner of IκB kinase β, one of the central signaling kinases activating the transcription factor nuclear factor—κB (NF-κB). Using endogenous protein levels of endothelial cell extracts, we could verify the interaction by coimmunoprecipitation experiments. Fluorescence resonance energy transfer (FRET) microscopy confirmed the direct interaction of CFP-IKKβ and YFPGMRα in living cells. Functional studies demonstrated GMCSF-dependent activation of IκB kinase activity in endothelial cells, degradation of IκB, and activation of NF-κB. Further biologic studies using GMCSF-dependent TF-1 cells indicated that GMCSF-triggered activation of NF-κB is important for cell survival and proliferation. (Blood. 2003;102:192-199)
On using experimentally estimated wall shear stresses to validate numerically predicted results
Authors: Walsh M , McGloughlin T , Liepsch D W , O'Brien T , Morris L , Ansari A R 
Published: March 2003

The objective of this investigation was to assess the use of experimentally estimated wall shear stresses to validate numerically predicted results. The most commonly cited haemodynamic factor implicated in the disease initiation and proliferation processes at graft/artery junctions is wall shear stress (WSS). WSS can be determined from the product of the viscosity of the fluid and the wall shear rate. Numerically, the wall shear rate is predicted using velocity values stored in the computational cell near the wall and assuming zero velocity at the wall. Experimentally, the wall shear rate is estimated by applying a curve-fit to near-wall velocity measurements and evaluating the shear rate at a specific distance from the wall. When estimating the wall shear rate from the laser Doppler anemometry (LDA) point velocity measurements, large differences between the experimentally estimated and numerically predicted WSSs were introduced. It was found that the estimated WSS distributions from the experimental results are highly dependent on the curve-fitting method used to calculate the wall shear rate. However, the velocity profiles for both the experimental and numerical investigations show extremely good comparison. It is concluded that numerical models should be validated using unprocessed LDA point velocity measurement and not estimated WSS values.
Reduced Quality of Life in Survivors of Acute Respiratory Distress Syndrome Compared With Critically Ill Control Patients
Authors: Davidson Timothy A. , Caldwell Ellen S. , Curtis J. Randall , Hudson Leonard D. , Steinberg Kenneth P. 
Published: March 2003

ContextHealth-related quality of life (HRQL) is reduced in patients who survive acute respiratory distress (ARDS), but whether this decline in HRQL is caused by ARDS or other aspects of the patient's illness or injury is unknown.ObjectiveTo determine if there are differences in the HRQL of ARDS survivors and comparably ill or injured controls without ARDS.DesignProspective, matched, parallel cohort study.SettingA 411-bed municipal medical and regional level I trauma center.PatientsSeventy-three pairs of ARDS survivors and severity-matched controls with the clinical risk factors for ARDS of sepsis and trauma admitted between January 1, 1994, and July 30, 1996.Main Outcome MeasuresThe HRQL of ARDS survivors and controls, assessed by generic and pulmonary disease–specific HRQL instruments (Medical Outcomes Study 36-Item Short Form Health Survey, Standard Form [SF-36] and St George's Respiratory Questionnaire [SGRQ], respectively).ResultsClinically meaningful and statistically significant reductions in HRQL scores of ARDS survivors (n=73) were seen in 7 of 8 SF-36 domains and 3 of 3 SGRQ domains compared with matched controls (P&amp;lt;.001 for all reductions). The largest decrements in the HRQL were seen in physical function and pulmonary symptoms and limitations. Analysis of trauma-matched pairs (n=46) revealed significant reductions in 7 of 8 SF-36 domains (P≤.02) and 3 of 3 SGRQ domains (P≤.003). Analysis of sepsis-matched pairs (n=27) revealed significant reductions in 6 of 8 SF-36 domains (P≤.05) and 3 of 3 SGRQ domains (P≤.002).ConclusionsSurvivors of ARDS have a clinically significant reduction in HRQL that appears to be caused exclusively by ARDS and its sequelae. Reductions were primarily noted in physical functioning and pulmonary disease–specific domains.
Self-referral in Point-of-Service Health Plans
Authors: Forrest Christopher B. , Weiner Jonathan P. , Fowles Jinnet , Vogeli Christine , Frick Kevin D. , Lemke Klaus W. , Starfield Barbara 
Published: March 2003

ContextMost health maintenance organizations offer products with loosened restrictions on patients' access to specialty care. One such product is the point-of-service (POS) plan, which combines "gatekeeping" arrangements with the ability to self-refer at increased out-of-pocket costs. Few data are available from formal evaluations of this new type of plan.ObjectivesTo comprehensively describe the self-referral process in POS plans by quantifying rates of self-referral, identifying patients most likely to self-refer, characterizing patients' reasons for self-referral, and assessing satisfaction with specialty care.DesignRetrospective cohort analysis using administrative databases composed of members aged 0 to 64 years who were enrolled in 3 POS health plans in the Midwest (n = 265 843), Northeast (n = 80 292), and mid-Atlantic (n = 39 888) regions for 6 to 12 months in 1996, and a 1997 telephone survey of specialty care users (n = 606) in the midwestern plan.Main Outcome MeasuresSelf-referred service use and charges, reasons for self-referral, and satisfaction with specialty care.ResultsOverall, 8.8% of enrollees in the midwestern POS plan, 16.7% in the northeastern plan, and 17.3% in the mid-Atlantic plan self-referred for at least 1 physician or nonphysician clinician visit. The proportions of enrollees self-referring to generalists (4.7%-8.5%) were slightly higher than the proportions self-referring to specialists (3.7%-7.2%) across all 3 plans. Nine percent to 16% of total charges were due to self-referral. The chances of self-referral to a specialist were increased for patients with chronic and orthopedic conditions, higher cost sharing for physician-approved services, and less continuity with their regular physician. Patients who self-referred to specialists preferred to access specialty care directly (38%), reported relationship problems with their regular physicians (28%), had an ongoing relationship with a specialist (23%), were confused about insurance rules (8%), and did not have a regular physician (3%). Compared with those referred to specialists by a physician, patients who self-referred were more satisfied with the specialty care they received.ConclusionsHaving the option to self-refer is enough for most POS plan enrollees; 93% to 96% of enrollees did not exercise their POS option to obtain specialty care via self-referral during a 1-year interval. The potential downside of uncoordinated, self-referred service use in POS health plans is limited and counterbalanced by higher patient satisfaction with specialist services.
Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure
Authors: Rathore Saif S. , Curtis Jeptha P. , Wang Yongfei , Bristow Michael R. , Krumholz Harlan M. 
Published: March 2003

ContextThe Digitalis Investigation Group (DIG) trial reported that digoxin provided no overall mortality benefit and only a modest reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function. The clinical outcomes associated with digoxin therapy at different serum concentrations in the DIG trial have not been assessed.ObjectiveTo assess variations in serum digoxin concentration (SDC) and their association with mortality and hospitalization in patients with heart failure.Design, Setting, and PatientsPost hoc analysis of the randomized, double-blinded, placebo-controlled DIG trial, conducted from August 1991 to December 1995, with the main analysis restricted to men with a left ventricular ejection fraction of 45% or less (n = 3782). Patients randomly assigned to receive digoxin were divided into 3 groups based on SDC at 1 month (0.5-0.8 ng/mL, n = 572; 0.9-1.1 ng/mL, n = 322; and ≥1.2 ng/mL, n = 277) and compared with patients randomly assigned to receive placebo (n = 2611).Main Outcome MeasureAll-cause mortality at a mean follow-up of 37 months.ResultsHigher SDCs were associated with increased crude all-cause mortality rates (0.5-0.8 ng/mL, 29.9%; 0.9-1.1 ng/mL, 38.8%; and ≥1.2 ng/mL, 48.0%; P = .006 for trend). Patients with SDCs of 0.5 to 0.8 ng/mL had a 6.3% (95% confidence interval [CI], 2.1%-10.5%) lower mortality rate compared with patients receiving placebo. Digoxin was not associated with a reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL (2.6% increase; 95% CI, − 3.0% to 8.3%), whereas patients with SDCs of 1.2 ng/mL and higher had an 11.8% (95% CI, 5.7%-18.0%) higher absolute mortality rate than patients receiving placebo. The association between SDC and mortality persisted after multivariable adjustment (SDC 0.5-0.8 ng/mL hazard ratio [HR] 0.80, 95% CI, 0.68-0.94; SDC 0.9-1.1 ng/mL HR 0.89, 95% CI, 0.74-1.08; SDC ≥1.2 ng/mL HR 1.16, 95% CI, 0.96-1.39; and HR of 1.00 [referent] for placebo).ConclusionsOur findings demonstrate that higher SDCs were associated with increased mortality and suggest that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL.
Use of Child Booster Seats in Motor Vehicles Following a Community Campaign
Authors: Ebel Beth E. , Koepsell Thomas D. , Bennett Elizabeth E. , Rivara Frederick P. 
Published: March 2003

ContextOnce children have outgrown car seats, booster seats protect from injury better than lap and shoulder belts alone. However, the majority of children aged 4 to 8 years use only an adult seat belt.ObjectiveTo evaluate the effectiveness of a multifaceted community booster seat campaign in increasing observed booster seat use among child passengers in motor vehicles.DesignProspective, nonrandomized, controlled community intervention trial.Setting and ParticipantsThe campaign was initiated in 4 communities in the greater Seattle, Wash, area between January 2000 and March 2001. Eight communities in Portland, Ore, and Spokane, Wash, served as control sites. We observed 3609 booster-eligible children (those aged 4-8 years and weighing 18-36 kg [40-80 lb]).Main Outcome MeasureObserved booster seat use 15 months after the start of the campaign.ResultsBefore the campaign began, 13.3% of eligible children in the intervention communities and 17.3% in the control communities were using booster seats, adjusting for child age, driver seat belt use, and sex of driver. Fifteen months after the start of the campaign, adjusted booster seat use had increased to 26.1% in the intervention communities and 20.2% in the control communities (P = .008 for the difference in time trends between intervention and control communities).ConclusionThese data suggest that a multifaceted community education campaign can significantly increase the use of child booster seats.
Patients' and Physicians' Attitudes Regarding the Disclosure of Medical Errors
Authors: Gallagher Thomas H. , Waterman Amy D. , Ebers Alison G. , Fraser Victoria J. , Levinson Wendy 
Published: March 2003

ContextDespite the best efforts of health care practitioners, medical errors are inevitable. Disclosure of errors to patients is desired by patients and recommended by ethicists and professional organizations, but little is known about how patients and physicians think medical errors should be discussed.ObjectiveTo determine patients' and physicians' attitudes about error disclosure.Design, Setting, and ParticipantsThirteen focus groups were organized, including 6 groups of adult patients, 4 groups of academic and community physicians, and 3 groups of both physicians and patients. A total of 52 patients and 46 physicians participated.Main Outcome MeasuresQualitative analysis of focus group transcripts to determine the attitudes of patients and physicians about medical error disclosure; whether physicians disclose the information patients desire; and patients' and physicians' emotional needs when an error occurs and whether these needs are met.ResultsBoth patients and physicians had unmet needs following errors. Patients wanted disclosure of all harmful errors and sought information about what happened, why the error happened, how the error's consequences will be mitigated, and how recurrences will be prevented. Physicians agreed that harmful errors should be disclosed but "choose their words carefully" when telling patients about errors. Although physicians disclosed the adverse event, they often avoided stating that an error occurred, why the error happened, or how recurrences would be prevented. Patients also desired emotional support from physicians following errors, including an apology. However, physicians worried that an apology might create legal liability. Physicians were also upset when errors happen but were unsure where to seek emotional support.ConclusionsPhysicians may not be providing the information or emotional support that patients seek following harmful medical errors. Physicians should strive to meet patients' desires for an apology and for information on the nature, cause, and prevention of errors. Institutions should also address the emotional needs of practitioners who are involved in medical errors.