bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Because 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

All-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

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)
Ssdp proteins bind to LIM-interacting co-factors and regulate the activity of LIM-homeodomain protein complexes in vivo
Authors: van Meyel Donald J. , Thomas John B. , Agulnick Alan D.
Published: March 2003

LIM-homeodomain transcription factors control a variety of developmental processes, and are assembled into functional complexes with the LIM-binding co-factor Ldb1 (in mouse) or Chip (in Drosophila). We describe the identification and characterization of members of the Ssdp family of proteins,which we show to interact with Ldb1 and Chip. The N terminus of Ssdp is highly conserved among species and binds a highly conserved domain within Ldb1/Chip that is distinct from the domains required for LIM binding and self-dimerization. In Drosophila, Ssdp is expressed in the developing nervous system and imaginal tissues, and it is capable of modifying the in vivo activity of complexes comprised of Chip and the LIM-homeodomain protein Apterous. Null mutations of the ssdp gene are cell-lethal in clones of cells within the developing wing disc. However, clones mutant for a hypomorphic allele give rise to ectopic margins, wing outgrowth and cell identity defects similar to those produced by mutant clones of Chipor apterous. Ssdp and Ldb/Chip each show structural similarity to twoArabidopsis proteins that cooperate with one another to regulate gene expression during flower development, suggesting that the molecular interactions between Ssdp and Ldb/Chip proteins are evolutionarily ancient and supply a fundamental function in the regulated control of transcription.
Cell-autonomous involvement ofMab21l1is essential for lens placode development
Authors: Yamada Ryuichi , Mizutani-Koseki Yoko , Hasegawa Takanori , Osumi Noriko , Koseki Haruhiko , Takahashi Naoki
Published: March 2003

The mab-21 gene was first identified because of its requirement for ray identity specification in Caenorhabditis elegans. It is now known to constitute a family of genes that are highly conserved from vertebrates to invertebrates, and two homologs, Mab21l1 andMab21l2, have been identified in many species. We describe the generation of Mab21l1-deficient mice with defects in eye and preputial gland formation. The mutant mouse eye has a rudimentary lens resulting from insufficient invagination of the lens placode caused by deficient proliferation. Chimera analyses suggest that the lens placode is affected in a cell-autonomous manner, although Mab21l1 is expressed in both the lens placode and the optic vesicle. The defects in lens placode development correlate with delayed and insufficient expression ofFoxe3, which is also required for lens development, while Maf,Sox2, Six3 and PAX6 levels are not significantly affected. Significant reduction of Mab21l1 expression in the optic vesicle and overlying surface ectoderm in Sey homozygotes indicates that Mab21l1expression in the developing eye is dependent upon the functions ofPax6 gene products. We conclude that Mab21l1 expression dependent on PAX6 is essential for lens placode growth and for formation of the lens vesicle; lack of Mab21l1 expression causes reduced expression of Foxe3 in a cell-autonomous manner.
XMAN1, an inner nuclear membrane protein, antagonizes BMP signaling by interacting with Smad1 inXenopusembryos
Authors: Osada Shin-Ichi , Ohmori Shin-ya , Taira Masanori
Published: March 2003

A family of inner nuclear membrane proteins is implicated in gene regulation by interacting with chromatin, nuclear lamina and intranuclear proteins; however, the physiological functions of these proteins are largely unknown. Using a Xenopus expression screening approach with an anterior neuroectoderm cDNA library, we have identified an inner nuclear membrane protein, XMAN1, as a novel neuralizing factor that is encoded by theXenopus ortholog of human MAN1. XMAN1 mRNA is expressed maternally, and appears to be restricted to the entire ectoderm at the early gastrula stage, then to the anterior neuroectoderm at the neurula stage. XMAN1 induces anterior neural markers without mesoderm induction in ectodermal explants, and a partial secondary axis when expressed ventrally by dorsalizing the ventral mesoderm. Importantly, XMAN1 antagonizes bone morphogenetic protein (BMP) signaling downstream of its receptor Alk3, as judged by animal cap assays, in which XMAN1 blocks expression of downstream targets of BMP signaling (Xhox3 and Msx1), and by luciferase reporter assays, in which XMAN1 suppresses BMP-dependent activation of theXvent2 promoter. Deletion mutant analyses reveal that the neuralizing and BMP-antagonizing activities of XMAN1 reside in the C-terminal region, and that the C-terminal region binds to Smad1, Smad5 and Smad8, which are intracellular mediators of the BMP pathway. Interference with endogenous XMAN1 functions with antisense morpholino oligos leads to the reduction of anterior neuroectoderm. These results provide the first evidence that the nuclear envelope protein XMAN1 acts as a Smad-interacting protein to antagonize BMP signaling during Xenopus embryogenesis.
Twotcf3genes cooperate to pattern the zebrafish brain
Authors: Dorsky Richard I. , Itoh Motoyuki , Moon Randall T. , Chitnis Ajay
Published: March 2003

Caudalizing factors operate in the context of Wnt/β-catenin signaling to induce gene expression in discrete compartments along the rostral-caudal axis of the developing vertebrate nervous system. In zebrafish, basal repression of caudal genes is achieved through the function of Headless (Hdl),a Tcf3 homolog. In this study, we show that a second Tcf3 homolog, Tcf3b,limits caudalization caused by loss of Hdl function and although this Lef/Tcf family member can rescue hdl mutants, Lef1 cannot. Wnts can antagonize repression mediated by Tcf3 and this derepression is dependent on a Tcf3 β-catenin binding domain. Systematic changes in gene expression caused by reduced Tcf3 function help predict the shape of a caudalizing activity gradient that defines compartments along the rostral-caudal axis. In addition, Tcf3b has a second and unique role in the morphogenesis of rhombomere boundaries, indicating that it controls multiple aspects of brain development.
LvTbx2/3: a T-box family transcription factor involved in formation of the oral/aboral axis of the sea urchin embryo
Authors: Gross Jeffrey M. , Peterson Robert E. , Wu Shu-Yu , McClay David R.
Published: March 2003

T-box family transcription factors have been identified in many organisms and are frequently associated with patterning events during embryonic development. With an interest in the molecular basis of patterning in the sea urchin embryo, we identified several members of the T-box family inLytechinus variegatus. Here, we report the cloning and characterization of an ortholog of the Tbx2/3 subfamily, LvTbx2/3. To characterize the spatial distribution of LvTbx2/3 protein throughout sea urchin embryogenesis, a polyclonal antiserum was generated. Nuclear localization of LvTbx2/3 initiated at the mesenchyme blastula stage and protein was present into the pluteus stage. Localization was asymmetric throughout this period and costaining with marker genes indicated that asymmetry was about the oral/aboral (O/A) axis. Asymmetric distribution of LvTbx2/3 was observed in the aboral territories of all three germ layers. In the skeletogenic mesoderm lineage, LvTbx2/3 expression was dynamic because expression appeared initially in all skeletogenic mesenchyme cells (PMCs) but,subsequently, became refined solely to the aboral ones during skeletogenesis. To determine if the aboral expression of LvTbx2/3 is linked between germ layers, and to place LvTbx2/3 in the sequence of events that specifies the O/A axis, the effects of a series of perturbations to O/A polarity on LvTbx2/3 expression in each germ layer were examined. Preventing the nuclear localization of β-catenin, pharmacological disruption of the O/A axis with NiCl2, overexpression ofBMP2/4 and disruption of the extracellular matrix all blockedLvTbx2/3 expression in all germ layers. This indicates that expression of LvTbx2/3 in the aboral territories of each germ layer is a common aspect of O/A specification, downstream of the molecular events that specify the axis. Furthermore, blocking the nuclear localization ofβ-catenin, overexpression of BMP2/4 and disruption of the extracellular matrix also prevented the oral (stomodael) expression of LvBrachyury (LvBrac) protein, indicating that the O/A axis is established by a complex series of events. Last, the function of LvTbx2/3 in the formation of the O/A axis was characterized by examining the phenotypic consequences of ectopic expression of LvTbx2/3 mRNA on embryonic development and the expression of marker genes that identify specific germ layers and tissues. Ectopic expression of LvTbx2/3 produced profound morphogenetic defects in derivatives of each germ layer with no apparent loss in specification events in those tissues. This indicates that LvTbx2/3 functions as a regulator of morphogenetic movements in the aboral compartments of the ectoderm, endoderm and mesoderm.
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.
Fatigue testing of a proximal femoral hip component
Authors: Macdonald W , Carlsson L V , Gathercole N , Jacobsson C M
Published: March 2003

The Gothenburg Osseointegrated Titanium (GOT) implant is a novel total hip replacement including a metaphyseal loading proximal femoral component fixed in the retained femoral neck. Endurance testing was performed under conditions analogous to ISO 7206–4: 1989. The cement-free implant is not fixed distally within the intramedullary canal, so distal embedding (as specified in the standard) would have been unrealistic. Instead glass-fibre-reinforced epoxy (GFRE) bushings were used to model reduced bone support mid-length at the medial cortex and distally at the lateral cortex. Such support simulated proximal bone loss, realistically reproducing the effect of osteolysis or fixation failure. Under such conditions the component survived unbroken for 10 million cycles at 3.0 kN peak load.
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

Context

Health-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.

Objective

To determine if there are differences in the HRQL of ARDS survivors and comparably ill or injured controls without ARDS.

Design

Prospective, matched, parallel cohort study.

Setting

A 411-bed municipal medical and regional level I trauma center.

Patients

Seventy-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 Measures

The 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).

Results

Clinically 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<.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).

Conclusions

Survivors 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

Context

Most 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.

Objectives

To 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.

Design

Retrospective 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 Measures

Self-referred service use and charges, reasons for self-referral, and satisfaction with specialty care.

Results

Overall, 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.

Conclusions

Having 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

Context

The 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.

Objective

To assess variations in serum digoxin concentration (SDC) and their association with mortality and hospitalization in patients with heart failure.

Design, Setting, and Patients

Post 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 Measure

All-cause mortality at a mean follow-up of 37 months.

Results

Higher 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).

Conclusions

Our 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

Context

Once 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.

Objective

To evaluate the effectiveness of a multifaceted community booster seat campaign in increasing observed booster seat use among child passengers in motor vehicles.

Design

Prospective, nonrandomized, controlled community intervention trial.

Setting and Participants

The 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 Measure

Observed booster seat use 15 months after the start of the campaign.

Results

Before 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).

Conclusion

These 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

Context

Despite 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.

Objective

To determine patients' and physicians' attitudes about error disclosure.

Design, Setting, and Participants

Thirteen 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 Measures

Qualitative 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.

Results

Both 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.

Conclusions

Physicians 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.
Advanced Access
Authors: Murray Mark , Berwick Donald M.
Published: March 2003

Delay of care is a persistent and undesirable feature of current health care systems. Although delay seems to be inevitable and linked to resource limitations, it often is neither. Rather, it is usually the result of unplanned, irrational scheduling and resource allocation. Application of queuing theory and principles of industrial engineering, adapted appropriately to clinical settings, can reduce delay substantially, even in small practices, without requiring additional resources. One model, sometimes referred to asadvanced access, has increasingly been shown to reduce waiting times in primary care. The core principle of advanced access is that patients calling to schedule a physician visit are offered an appointment the same day. Advanced access is not sustainable if patient demand for appointments is permanently greater than physician capacity to offer appointments. Six elements of advanced access are important in its application

balancing supply and demand, reducing backlog, reducing the variety of appointment types, developing contingency plans for unusual circumstances, working to adjust demand profiles, and increasing the availability of bottleneck resources. Although these principles are powerful, they are counter to deeply held beliefs and established practices in health care organizations. Adopting these principles requires strong leadership investment and support.
Improving Timely Access to Primary Care
Authors: Murray Mark , Bodenheimer Thomas , Rittenhouse Diane , Grumbach Kevin
Published: March 2003

The advanced access model of patient scheduling is based on the core principle that if the capacity to provide patient appointments balances the demand for appointments, patients calling to see their physician are offered an appointment the same day. The accompanying article in the series "Innovations in Primary Care" presents the theory behind advanced access scheduling. In this article we describe 4 case studies of primary care practices that successfully implemented advanced access and 3 examples of practices that were unable to achieve advanced access despite considerable efforts. The lessons of these case studies should be useful for primary care practices desiring to improve timely access to care and wishing to avoid the pitfalls that can derail this innovation.
Staff survey results and characteristics that predict assault and injury to personnel working in mental health facilities
Authors: Cunningham Julie , Connor Daniel F. , Miller Kevin , Melloni Richard H.
Published: March 2003

The purpose of this study was to complete a mental health staff opinion survey to identify patient and staff characteristics associated with staff assault and injury in psychiatric treatment settings and to develop a model of prediction for staff assault and injury utilizing these survey variables. The data consisted of opinion surveys sent to staff of 15 child, adolescent, and adult psychiatry inpatient units in the United States. Multivariate logistic regression was used to determine the level of assault and staff‐reported injury prediction that could be obtained from the staff‐completed opinion survey. Responses indicated a high prevalence of reported aggression, with 62.3% of staff endorsing verbal and physical aggression, property destruction, and self‐injurious behavior as being prevalent at their site, whereas only 4.1% rated none of these as prevalent. Staff working with children and adolescents in settings with high rates of psychiatric diagnoses reported increased frequency of assault and injury compared with those working with adults. Younger, less experienced staff reported higher rates of assault and injury. Staff working with female patients reported similar rates of assault and injury to those working with males. A logistic regression analysis using staff‐reported survey results of both staff and patient characteristics predicted assault correctly 73.7% of the time and injury 66.1% of the time. Resources for violence prevention and staff training programs in violence prevention are needed in child and adolescent psychiatry wards. Results are consistent with theories emphasizing the importance of negative emotions and affects, impulsivity, and frustration in goal‐directed activities in human aggression. Aggr. Behav. 29:31–40, 2003. © 2003 Wiley‐Liss, Inc.
Strain‐specific aggressive behavior of male mice submitted to different husbandry procedures
Authors: Van Loo P.L.P. , Van der Meer E. , Kruitwagen C.L.J.J. , Koolhaas J.M. , Van Zutphen L.F.M. , Baumans V.
Published: March 2003

Severe aggression within groups of male laboratory mice can cause serious welfare problems. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning and the provision of nesting material decrease aggression and stress in group‐housed male mice. In this study, the combined effect of these husbandry procedures was tested for their long‐term effect on aggression in two strains of male mice (BALB/c and CD‐1). We used postcleaning aggressive behavior, wound counts, and testosterone levels as indicators of aggressiveness. Physiological responses to social challenge were investigated through urinary corticosterone and adrenal tyrosine‐hydroxylase measurements. Furthermore, the aggression‐modulating effects of two enrichment items (ShepherdShack/DesRes and PVC tube) were explored. Marked differences were found between the two strains. CD‐1 mice were more aggressive, had higher testosterone levels but lower corticosterone levels, and had fewer wounds than BALB/c mice. However, in neither of the two strains was long‐term enrichment with nesting material and its transfer after cage cleaning effective in lasting reduction of intermale aggression. This may be explained by the fact that aggression levels were generally low. It seems that housing mice in small, socially stable groups or keeping social disturbances to a minimum considerably modulates aggression in group‐housed male mice. Mice of both strains housed in cages enriched with nesting material had lower urinary corticosterone levels than standard‐housed mice. We therefore conclude that the long‐term provision of nesting material, including the transfer of nesting material during cage cleaning, may enhance the welfare of laboratory mice. Aggr. Behav. 29:69–80, 2003. © 2002 Wiley‐Liss, Inc.
Cognitive procedures for correcting proxy‐response biases in surveys
Authors: Todorov Alexander
Published: March 2003

To reduce survey costs, major surveys rely on self‐ and proxy‐responses. The use of proxies can reduce data quality introducing biases in the survey estimates. This paper identifies one source of systematic differences between self‐ and proxy‐reports: proxies' higher reliance on inferences. Using data from the National Health Interview Survey on Disability (NHIS‐D), proxy‐response biases were modelled by independently collected measures of cognitive inferences. Conditional likelihood judgements about a number of disabilities (e.g. likelihood that a person has a disability given another disability) predicted the conditional disability reports for proxy‐ but not for self‐respondents (e.g. the proportion of respondents who reported difficulty learning after reporting difficulty communicating). A model of self/proxy differences was estimated on data from the 1994 NHIS‐D and tested against 1995 data. The correlation between predicted and actual differences was 0.76. The correlation between predicted and actual proxy‐reports was 0.95. Such research can be used to estimate and correct for systematic proxy‐response biases. Copyright © 2002 John Wiley & Sons, Ltd.
Verbal overshadowing of multiple face and car recognition: effects of within‐ versus across‐category verbal descriptions
Authors: Brown Charity , Lloyd‐Jones Toby J.
Published: March 2003

We present four experiments examining ‘verbal overshadowing’ (the phenomenon that verbally describing a stimulus can interfere with subsequent recognition of that stimulus) using a new multiple stimuli presentation paradigm. Participants are exposed to 12 to‐be‐remembered stimuli (faces or cars) and then describe (or not, in the control condition) a related stimulus (a 13th face or car). Subsequently, participants have to discriminate the original 12 stimuli from 12 distracters (in a ‘yes/no’ recognition decision). Verbal overshadowing occurs for both accuracy and response times for both face and car recognition, when participants have previously described a face. When participants describe a car prior to recognition, however, verbal overshadowing does not occur. We argue that (1) the paradigm provides a new tool for studying verbal overshadowing and (2) verbal overshadowing is not ‘semantic category‐bound’ (i.e. limited to describing stimuli within the same semantic category). We interpret these findings within a ‘transfer‐inappropriate retrieval’ framework (Schooler et al., 1997). Copyright © 2002 John Wiley & Sons, Ltd.
Spontaneous Vertical Ordering and Pyrolytic Formation of Nanoscopic Ceramic Patterns from Poly(styrene‐b‐ferrocenylsilane)
Authors: Temple K. , Kulbaba K. , Power‐Billard K.N. , Manners I. , Leach K.A. , Xu T. , Russell T.P. , Hawker C.J.
Published: March 2003

The rapid generation of nanopatterned surfaces using thin films of the amorphous diblock copolymer poly(styrene‐b‐ferrocenylethylmethylsilane) (PS‐b‐PFS) is reported. Spontaneous self‐assembly into vertically oriented cylinders of PFS in a PS matrix is observed on a variety of substrates by spin or dip coating, irrespective of the substrate surface polarity. Pyrolysis of the films affords arrays of 20 nm Fe‐containing ceramic nanoparticles, (see Figure, AFM, 4 μm2 scan area).
A Novel Method for Preparing Copper Nanorods and Nanowires
Authors: Liu Z. , Bando Y.
Published: March 2003

Vacuum vapor deposition of copper nanorods and nanowires (see Figure) is reported. This novel one‐step procedure involves copper vapor generation and redeposition on a substrate under very low pressure or vacuum conditions. Nanorods and nanowires of a variety of materials apart from copper, e.g., other metals, alloys, and semiconductors, can also be synthesized using this method.
Supercritical Fluid Fabrication of Metal Nanowires and Nanorods Templated by Multiwalled Carbon Nanotubes
Authors: Ye X.‐R. , Lin Y. , Wang C. , Wai C.M.
Published: March 2003

Metal nanorods and nanowires (see Figure) have been synthesized using multiwalled carbon nanotubes (MWCNTs) as templates and supercritical CO2 as the reaction medium. This rapid, direct, and clean approach can also be used to fabricate other metal/CNT composites and to coat the CNTs with metal films or nanoparticles.
Laser‐Writable, Electrically Erasable Photoelectrochromic Organic Film
Authors: Macchione M. , De Filpo G. , Mashin A. , Nicoletta F.P. , Chidichimo G.
Published: March 2003

An organic photoelectrochromic film, in which methylene blue can change from blue to transparent on absorption of light, and return to blue by an oxidation reaction induced by an external electric field, is presented (see Figure). The resulting device presents the remarkable advantage of being driven by a red HeNe laser (5 mW) for the “writing process”, and by a very low voltage (0.4 V) for the “erasing process”.
Semiconductor Nanorod Liquid Crystals and Their Assembly on a Substrate
Authors: Li L.‐S. , Alivisatos A.P.
Published: March 2003

The macroscopic alignment and superlattice structures of CdSe nanorods in a nematic liquid‐crystalline (LC) phase are determined by the phases that form prior to complete solvent evaporation (e.g., vortex structures in linear arrays, see Figure). By controlling the phase of the LC solution and its orientation using pretreated surfaces or external fields, it may be possible to achieve fine control of order in deposited nanorod films.
Solution–Liquid–Solid Growth of Soluble GaAs Nanowires
Authors: Yu H. , Buhro W.E.
Published: March 2003

GaAs nanowires exhibiting narrow diameter distributions and small diameters within and near the strong‐confinement regime can be generated using the solution–liquid–solid (SLS) mechanism (see Figure for 5.99 nm diameter wires). A relationship between the mean diameters of the nanowires and the indium catalyst nanoparticles from which the nanowires are grown is furthermore established.
Single‐Crystalline Barium Titanate Nanowires
Authors: Urban J.J. , Spanier J.E. , Ouyang L. , Yun W.S. , Park H.
Published: March 2003

Single‐crystalline barium titanate nanowires are synthesized using a solution‐based method, and their ferroelectric properties are investigated by scanning probe microscopy. Pristine nanowires have diameters ranging from 5 to 70 nm and lengths exceeding 10 μm, and they possess perovskite structures with a principal axis aligned along the wire axis. Scanning probe microscopy investigations show that local non‐volatile electric polarization can be reproducibly induced and manipulated on nanowires as small as 10 nm in diameter.
Nanobelts, Nanowires, and Nanodiskettes of Semiconducting Oxides—From Materials to Nanodevices
Authors: Wang Z.L.
Published: March 2003

Novel nanostructures of semiconducting oxides are reviewed here. It is shown that nanobelts, nanowires, and nanodiskettes of materials such as zinc oxide, gallium oxide, silica, and tin oxide can be fabricated using a vapor‐phase evaporation method. Two applications of these materials—in field effect transistors and as gas sensors—are highlighted.
Supercritical Fluid–Liquid–Solid (SFLS) Synthesis of Si and Ge Nanowires Seeded by Colloidal Metal Nanocrystals
Authors: Hanrath T. , Korgel B.A.
Published: March 2003

Semiconductor nanowires, 5 to 20 nm in diameter and micrometers in length, appear to be promising candidates for a variety of new technologies, including computing, memory, and sensor applications. Suitable for these applications, silicon (Si) and germanium (Ge) nanowires ranging from 4 to 30 nm in diameter and micrometers in length can be produced in high temperature supercritical fluids by thermally degrading organosilane or organogermane precursors in the presence of organic‐monolayer‐protected gold nanocrystals. Although gas phase vapor–liquid–solid (VLS) methods can be used to produce a variety of different nanowire materials, high temperature supercritical fluids provide wire size control through nanocrystal size selection prior to synthesis, and high product yields due to the high precursor solubility.
Rational Synthesis of Metal Nanotubes and Nanowires from Lamellar Structures
Authors: Wang J. , Li Y.
Published: March 2003

A generic method has been developed for the synthesis of crystalline metal nanowires or nanotubes (such as bismuth nanotubes, tungsten nanowires) from lamellar structures. In a typical process, lamellar surfactant/inorganic composite precursors are first prepared by reacting cationic or anionic surfactants with inorganic species under appropriate conditions. After treating these precursors by hydrothermal pyrolysis, or other processes, crystalline metallic nanotubes or nanowires are obtained.
Solvothermal Route to Semiconductor Nanowires
Authors: Tang K.‐B. , Qian Y.‐T. , Zeng J.‐H. , Yang X.‐G.
Published: March 2003

Solvothermal synthesis is an important technology for the preparation of nanowires at low temperature. Nanowires can grow as long as 100 μm with the aid of polymer matrix, and under the pressure generated by solvothermal reactions, the as‐prepared nanowires are well crystallized. For water‐sensitive reactions, solvothermal reactions can fully avoid the presence of water. We discuss here the synthesis of a variety of nanowire structures, including CdS–CdSe core–sheath nanowires and very long CdS nanowires, and the solvothermal closure of PbS nanowires. Now that an appropriate procedure has been established, the solvothermal reactions are efficient and time‐saving.
Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal investigation of thromboembolism etiology (LITE)
Authors: Tsai Albert W. , Cushman Mary , Tsai Michael Y. , Heckbert Susan R. , Rosamond Wayne D. , Aleksic Nena , Yanez N. David , Psaty Bruce M. , Folsom Aaron R.
Published: March 2003

We sought to examine prospectively the association of serum homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphism with risk of venous thromboembolism (VTE). We studied these relationships in a nested case–control study of 303 VTE cases and 635 matched controls from a population‐based cohort of 21,680 adults from six U.S. communities. The highest quintile of serum homocysteine carried a non‐statistically significant adjusted odds ratio of 1.55 (95% CI, 0.93–2.58) compared to the lowest quintile in the overall cohort but a significant association among adults aged 45–64 years (OR = 2.05, 95% CI, 1.10–3.83) and an inverse association in those ≥65 years of age. Carriers of the MTHFR C677T polymorphism were not at higher risk for VTE than those with normal genotype (OR = 0.74, 95% CI = 0.56–0.98). Our prospective data showed, at most, a weak relationship between homocysteine and VTE risk, with associations larger among younger participants. MTHFR C677T was not a risk factor for VTE. Am. J. Hematol. 72:192–200, 2003. © 2003 Wiley‐Liss, Inc.
Dental variation of ryukyu islanders: A comparative study among Ryukyu, Ainu, and other Asian populations
Authors: Higa Takako , Hanihara Tsunehiko , Sunakawa Hajime , Ishida Hajime
Published: March 2003

The presence or absence of 24 nonmetric dental traits was examined to investigate the inter‐ and intraregional variation of Ryukyu Islanders. We compared the dentition of the Kadena sample from the central district of Okinawa Island in the Ryukyu Island chain to those of samples from Nakijin from the northern district of the same Okinawa Island, Tokunoshima, another island of the Ryukyu Island chain, main‐island Japanese in Kagoshima and Tokyo, Hokkaido Ainu, Atayal in Taiwan, and Pashtuns and Tajiks in Afghanistan. Many traits of the Ryukyu Islanders were found to be close to those of the main‐island Japanese; however, several were intermediate between those of the main‐island Japanese and the Ainu or Atayal. The intraregional variation in the Ryukyu Islanders was comparable to that in the main‐island Japanese. This result supports the influence of a complex gene flow to the Ryukyu Islanders, as suggested by some genetic studies. Among the populations compared here, that closest to the Ainu was the population of Tokunoshima. Am. J. Hum. Biol. 15:127–143, 2003. © 2003 Wiley‐Liss, Inc.
Impact of maternal age and maternal somatic characteristics on newborn size
Authors: Kirchengast Sylvia , Hartmann Beda
Published: March 2003

Pregnancies during early adolescence were commonly thought to represent special risks, such as preterm delivery or low‐weight newborns, resulting in increased mortality and morbidity of mother and child. An important biopsychosocial interaction can be assumed. In the present study the impact of maternal age and maternal somatic characteristics such as prepregnancy weight, stature, or pregnancy weight gain on newborn somatometric features (birth weight, birth length, head circumference, and arcomial circumference) using a dataset of 8,011 single term births were analyzed. The offspring of 215 extremely young mothers ages 12–16 years were significantly (P < 0.0001) lighter and smaller in all body dimensions than the offspring of older adolescent mothers, ages 17–19 years, and the offspring of adult gravida, ages 20–29 years, although no increased incidence of low‐weight newborns (<2,500g) could be observed. As expected, the youngest mothers were also significantly smaller and lighter than their older, biologically more mature counterparts, although the relative weight gain during pregnancy was highest in the youngest age group (23.4% vs. 22.9 and 22.1%, respectively). In general, age but also pregnancy weight gain and prepregnancy weight status were significantly associated with pregnancy outcome. Within term births taking place under sufficient psychosocial support, maternal somatic features had an important impact on newborn size. Am. J. Hum. Biol. 15:220–228, 2003. ©2003 Wiley‐Liss, Inc.