bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of a Medical Non‐Linear Drilling Device: The Influence of Twist and Wear on the Fatigue Behaviour of NiTi Wires Subjected to Bending Rotation
Authors: Wagner M. , Richter J. , Frenzel J. , Grönemeyer D. , Eggeler G. 
Published: April 2004

AbstractThis paper considers fundamental and experimental aspects associated with the engineering design of a medical, non‐linear drilling device which exploits shape memory pseudoelasticity of NiTi wires. For this application it is important that the NiTi wires have a good fatigue resistance. This is why the present authors have previously determined the influence of various parameters on cyclic life, crack growth and stress state of pseudoelastic wires subjected to bending rotation fatigue. The actual drilling device has to withstand twist in addition to bending rotation because the free rotation is constrained by friction between the drill head and the bone material. In addition, friction between the wire and a NiTi guiding tube results in wear and this may well promote fatigue crack nucleation. In this paper, we explain the function of the medical drill. We then report results on the effect of the additional parameters (1) twist and (2) wear on the fatigue life of thin pseudoelastic NiTi wires. We finally discuss the implications of our experimental results for the design process of the medical drilling device.
New drugs and treatment for respiratory syncytial virus
Authors: Maggon Krishan , Barik Sailen 
Published: April 2004

AbstractThe respiratory syncytial virus (RSV) is a global health problem affecting infants and the elderly and claiming more lives than AIDS in many parts of the world. Only two antibody drugs are approved for its prevention, and ribavarin, a relatively nonspecific antiviral, is used for treatment. In the mid‐1990s, a number of pharmaceutical and biotech companies initiated research programs against RSV. Together, the academic and the industrial R&D covered the whole spectrum of antibodies, vaccines, synthetic small molecule antiviral and antisense technology, and at one point, accounted for at least 25 active R&D programs. However, coincident to the marketing of the monoclonal antibody palivizumab (Synagis®) in 1998, a sharp decline in such projects ensued. Many companies recently cancelled RSV projects during a prioritisation of their R&D portfolios although the continuing medical need, large market size and sales projections clearly indicate that a safe and effective RSV drug or vaccine is likely to attain blockbuster status. Today RSV receives an insignificant fraction of the R&D budget compared with AIDS, for example. This article reviews the present status of the anti‐RSV regimen, covers drugs in the market and in development, and attempts to link basic research to industrial drug development, animal models of RSV, clinical trials, current clinical management, and present and future market projections. It is hoped that the unmet medical need of the victims of RSV will encourage continued involvement of the pharmaceutical and biotechnology industry in developing safe and effective prevention and treatments for RSV. Copyright © 2004 John Wiley & Sons, Ltd.
Generalized log‐rank test for mixed interval‐censored failure time data
Authors: Zhao Qiang , Sun Jianguo 
Published: April 2004

AbstractThis paper considers the problem of non‐parametric treatment comparisons when mixed interval‐censored failure time data are available, which often occurs in clinical trials and epidemiological studies. By mixed interval‐censored data, we mean that the survival time of interest is observed to belong to an interval or to be right‐censored. For the problem, we generalize the most commonly used log‐rank test for right‐censored survival data. Numerical studies are conducted and reported to evaluate and compare the proposed test with the existing method, which indicate that the presented method works well. We apply the method to a data set arising from an AIDS cohort study, that motivated the study. Copyright © 2004 John Wiley & Sons, Ltd.
Conflicts of interest in data monitoring of industry versus publicly financed clinical trials
Authors: Lachin John M. 
Published: April 2004

AbstractThe FDA Guidance, while highly appropriate for industry sponsored trials, need not be imposed on publicly (e.g. NIH) financed clinical trials. While the potential for conflicts of interest exist in the latter, they are in general manageable and pose an acceptable low risk of threatening the integrity of a study. However, the Guidance should heighten the awareness of all investigators in public trials to the potential for the appearance of conflicts and to the need for full and open participation in the management of dualities of interest. Copyright © 2004 John Wiley & Sons, Ltd.
Playing safe and preserving integrity: making the FDA model work
Authors: Wittes Janet 
Published: April 2004

AbstractThe proposed FDA model for Data Monitoring Committees (DMC) includes the recommendation to separate the reporting statistician from the co‐ordinating centre statistician. The former writes reports for the DMC; the latter is the statistician responsible for the statistical design of the trial, its ongoing day‐to‐day operation, and the final analysis of the data. This model, while protecting the scientific integrity of the trial, risks producing inadequate reports to the DMC unless the reporting statistician understands the trial and the database. This brief paper describes methods by which the reporting statistician can gain the knowledge necessary to produce informative reports. It also emphasizes that reports produced for the purpose of making decisions during the course of a trial differ in purpose, and should therefore differ in form, from reports summarizing the data and results at the end of the trial. Copyright © 2004 John Wiley & Sons, Ltd.
Independence of the statistician who analyses unblinded data
Authors: Siegel Jay P. , O'Neill Robert T. , Temple Robert , Campbell Gregory , Foulkes Mary A. 
Published: April 2004

AbstractThis discussion considers arguments for and against separating responsibility for the unblinded interim analysis of a clinical trial from responsibility for trial management and modifications to the ongoing trial. The degree to which one or different statisticians carry out these responsibilities and thus the degree of statistician independence for the two activities can vary, but a sponsor should recognize that giving a single statistician both responsibilities might limit flexibility in managing the trial, particularly with respect to modifying an ongoing trial. Published in 2004 by John Wiley & Sons, Ltd.
The role of the unblinded sponsor statistician
Authors: Snapinn Steven , Cook Thomas , Shapiro Deborah , Snavely Duane 
Published: April 2004

AbstractIn clinical trials sponsored by Merck the unblinded statistician is typically an employee of the company. From a pharmaceutical industry perspective, advantages of this approach include ensuring that the unblinded statistician is knowledgeable regarding the experimental treatments, therapeutic area and study objectives; that the quality of the analysis conforms to rigorous standards; and that the allocation schedule, database and interim results are kept confidential. These advantages are felt to outweigh any potential disadvantages. Copyright © 2004 John Wiley & Sons, Ltd.
A thermogravimetric analysis study of volatilization of flux mixtures used in XRF sample preparation
Authors: Loubser Maggi , Strydom Christien , Potgieter Herman 
Published: April 2004

AbstractThis paper deals with the thermal behaviour occurring during the formation of lithium borate glasses. Thermogravimetric analysis and differential scanning calorimetry were employed to identify reactions occurring during fusion in pure flux mixtures. The conditions around the identified reactions were reproduced in a muffle furnace to obtain larger quantities of material for further investigation using spectroscopic techniques. It was shown that above 1050°C lithium borate fluxes volatilize, which could lead to inaccurate analytical results. Copyright © 2004 John Wiley & Sons, Ltd.
Self‐esteem, perception of relationships, and emotional distress: A cross‐cultural study
Authors: Abe Jo Ann A. 
Published: April 2004

AbstractThis study examined the relative importance of self‐esteem, family cohesion, and support from friends in predicting depressed mood and anxiety in Japanese and American college students. Contrary to expectations, self‐esteem was the strongest predictor of emotional distress in both groups of students. Nevertheless, consistent with predictions derived from Markus and Kitayama's theory of self‐construals, family cohesion accounted for a significantly larger percentage of the variance in predicting emotional distress in Japan than in the United States. In both countries, the relations between support from friends and the measures of emotional distress were entirely mediated by self‐esteem. However, among Japanese students, family cohesion accounted for additional significant variance in predicting the measures of emotional distress, even after controlling for self‐esteem.
The Power‐law Mathematical Model for Blood Damage Prediction: Analytical Developments and Physical Inconsistencies
Authors: Grigioni Mauro , Daniele Carla , Morbiducci Umberto , D’Avenio Giuseppe , Di Benedetto Giacomo , Barbaro Vincenzo 
Published: April 2004

Abstract:  Blood trauma caused by medical devices is a major concern. Complications following the implantation/application of devices such as prosthetic heart valves, cannulae, blood pumps, tubing, and throttles lead to sublethal and lethal damage to platelets and erythrocytes.This damage is provided by the alterations in fluid dynamics, providing a mechanical load on the blood corpuscle's membrane by means of the shear stress. An appropriate quantification of the shear‐induced hemolysis of artificial organs is thought to be useful in the design and development of such devices in order to minimize device‐induced blood trauma. To date, a power‐law mathematical relationship using the time of exposure of a blood corpuscle to a certain mechanical load and the shear stress itself (derived under the peculiar condition of uniform shear stress) has served as a basic model for the estimation of the damage to blood, investigated by means of numerical and/or experimental fluid dynamical techniques. The aim of the present article is to highlight the effect of a time‐varying mechanical loading acting on blood cells based on the usual power‐law model; furthermore, the effect of the loading history of a blood particle is discussed, showing how the past history of the shear acting on a blood corpuscle is not taken into account, as researchers have done until now. The need for a reassessment of the power‐law model for potential blood trauma assessment is discussed by using a mathematical formulation based on the hypotheses of the existence of damage accumulation for blood with respect to time and with respect to shear stress, to be applied in complex flow fields such as the ones established in the presence of artificial organs.
In vivo and in vitro studies onAnaplasma phagocytophiluminfection of the myeloid cells of a patient with chronic myelogenous leukaemia and human granulocytic ehrlichiosis
Authors: Bayard-Mc Neeley M , Bansal A , Chowdhury I , Girao G , Small C B , Seiter K , Nelson J , Liveris D , Schwartz I , Mc Neeley D F , Wormser G P , Aguero-Rosenfeld M E 
Published: April 2004

Aims:The occurrence of human granulocytic ehrlichiosis (HGE) in a patient with chronic myelogenous leukaemia (CML) provided an opportunity to study whetherAnaplasma phagocytophilum, the aetiological agent of HGE, infects mature or immature cells, both in vivo and in vitro.Methods:Diagnosis of HGE was confirmed by culture, polymerase chain reaction (PCR), detection of intragranulocytic inclusions, and serology. The infection rates of different myelogenous stages of granulocytic differentiation were determined by microscopy.Anaplasma phagocytophiluminfection of the bone marrow was analysed by PCR, culture, and microscopy. In addition, the in vitro growth ofA phagocytophilumin the patient’s granulocytes and in HL-60 cells (a promyelocytic leukaemia cell line) was compared.Results:Pretreatment blood smears showed that mature granulocytic cells had a higher infection rate withA phagocytophilumthan did immature cells. In the original inoculation of the patient’s cells into HL-60 cells to isolateA phagocytophilum, the bacterium grew faster in the patient’s leukaemic cells than in HL-60 cells.Anaplasma phagocytophiluminclusions were rarely seen in bone marrow granulocytes and PCR was negative. In vitro, twoA phagocytophilumisolates grew faster in the patient’s granulocytes than in HL-60 cells.Conclusions:The superior growth in CML cells compared with HL-60 cells suggests thatA phagocytophilumpreferentially infects mature granulocytes. The higher infection rate of the patient’s mature versus immature granulocytes before treatment and the minimal level of infection of the patient’s bone marrow support this. It is possible that the primary site of infection in HGE is the peripheral mature granulocytic population.
Matters of Life and Death: The Story of Elijah and the Widow's Son in Comparative Perspective
Authors: Lasine Stuart 
Published: April 2004

AbstractThis paper examines the concept of death projected by 1 Kgs 17:17-24 and other accounts of miraculous resuscitation. Viewed as a medical case history, Elijah's reviving of the widow's son raises difficult questions. Was the boy really dead, "only mostly dead," or merely gravely ill? Scholars often answer such questions by claiming that ancient Israelites did not consider corpses "to be 'totally' dead for a couple of days," and regarded death as "an enfeebled form of life." This paper challenges these claims by comparing Elijah's actions to those of other biblical and ancient Greek healers, as well as to Mesopotamian and shamanic healing practices. Why do healers like Elijah end up getting into bed with their patients? Examples in modern stories by Flaubert and Kafka reveal the kinship between the healer and the scapegoat, and suggest that miraculous healers tend to display narcissistic personality traits. Analysis of Greek sources and the Mount Horeb episode (1 Kings 19) indicates that this may also be the case for ancient healers like Elijah, Empedocles, and Asclepius, and that narcissism is itself a defense against death.
Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome
Authors: Markert M. Louise , Alexieff Marilyn J. , Li Jie , Sarzotti Marcella , Ozaki Daniel A. , Devlin Blythe H. , Sedlak Debra A. , Sempowski Gregory D. , Hale Laura P. , Rice Henry E. , Mahaffey Samuel M. , Skinner Michael A. 
Published: April 2004

AbstractComplete DiGeorge syndrome is a fatal congenital disorder characterized by athymia, hypoparathyroidism, and heart defects. Less than half of patients are 22q11 hemizygous. The goal of this study was to assess if immune suppression followed by postnatal thymus transplantation would lead to T-cell function in 6 infant patients who had host T cells at the time of transplantation. All infants had fewer than 50 recent thymic emigrants (CD3+CD45RA+CD62L+) per cubic millimeter (mm3) and all had some proliferative response to the mitogen phytohemagglutinin. Four infants had rash, lymphadenopathy, and oligoclonal populations of T cells in the periphery. Five of 6 patients are alive at the follow-up interval of 15 months to 30 months. The 5 surviving patients developed a mean of 983 host CD3+ T cells/mm3 (range, 536/mm3-1574/mm3), a mean of 437 recent thymic emigrants/mm3 (range, 196/mm3-785/mm3), and normal proliferative responses to phytohemaglutinin (follow-up from day 376 to day 873). The TCR repertoire became polyclonal in patients who presented with oligoclonal T cells. All patients had thymopoiesis on allograft biopsy. Postnatal thymus transplantation after treatment with Thymoglobulin shows promise as therapy for infants with complete DiGeorge syndrome who have significant proliferative responses to mitogens or who develop rash, lymphadenopathy, and oligoclonal T cells.
A TREM family member, TLT-1, is found exclusively in the α-granules of megakaryocytes and platelets
Authors: Washington A. Valance , Schubert Rebecca L. , Quigley Laura , Disipio Theresa , Feltz Robert , Cho Edward H. , McVicar Daniel W. 
Published: April 2004

AbstractThe triggering receptors expressed on myeloid cells (TREMs) have drawn considerable attention due to their ability to activate multiple cell types within the innate immune system, including neutrophils, monocyte/macrophages, and dendritic cells, via their association with DAP12. TLT-1 (TREM-like transcript-1) lies within the TREM gene cluster and contains the characteristic single V-set immunoglobulin (Ig) domain of the family, but its longer cytoplasmic tail is composed of both a proline-rich region and an immune receptor tyrosine-based inhibitory motif, the latter known to be used for interactions with protein tyrosine phosphatases. Here we report that TLT-1 is expressed exclusively in platelets and megakaryocytes (MKs) and that TLT-1 expression is up-regulated dramatically upon platelet activation. Consistent with this observation, confocal microscopy demonstrates that TLT-1 is prepackaged, along with CD62P, into both MK and platelet α-granules. Differences in thrombin-induced redistribution of CD62P and TLT-1 indicate that TLT-1 is not simply cargo of α-granules but may instead regulate granule construction or dispersal. Together these data show that that TLT-1 does not function to inhibit members of the TREM family but instead may play a role in maintaining vascular hemostasis and regulating coagulation and inflammation at sites of injury.
HCMV activates PI(3)K in monocytes and promotes monocyte motility and transendothelial migration in a PI(3)K-dependent manner
Authors: Smith M Shane , Bentz Gretchen L , Smith Patrick M , Bivins Elizabeth R , Yurochko Andrew D 
Published: April 2004

AbstractHuman cytomegalovirus (HCMV) is a leading cause of morbidity and mortality in immunocompromised hosts. In immunocompetent hosts, HCMV is associated with chronic inflammatory diseases including atherosclerosis. Monocytes and macrophages are proposed to play key roles in HCMV dissemination to host tissue, and their infection provides a biological link between the lifecycle of HCMV and disease pathology. We hypothesize that viral spread occurs via a mechanism in which infected peripheral blood monocytes, which are nonpermissive for viral replication, extravasate into host tissue and subsequently differentiate into permissive macrophages. Supporting this hypothesis, we recently showed that HCMV specifically induced the differentiation of monocytes into macrophages that become permissive for viral replication. To expand our understanding of HCMV pathogenesis, we next examined monocyte activation and migration, the first events in viral pathogenesis. We show here that HCMV up-regulates phosphatidylinositol 3,4,5 triphosphate kinase [PI(3)K] activity and that this increased PI(3)K activity is essential for infected monocyte-transendothelial migration. This increase in migration occurs through the up-regulation of cell motility in a PI(3)K-dependent process. Last, we show that these activated monocytes express a number of inflammatory mediators via PI(3)K signaling. We propose that the up-regulation of monocyte migration and immune mediators by HCMV infection is required for the hematogenous dissemination of the virus and as a consequence, could promote chronic inflammatory diseases associated with HCMV infection.
A Critical Role for the Evolutionarily Conserved Gonadotropin-Releasing Hormone II: Mediation of Energy Status and Female Sexual Behavior
Authors: Kauffman Alexander S. , Rissman Emilie F. 
Published: April 2004

Abstract
GnRH is an evolutionarily conserved neuropeptide, of which there are multiple structural variants; the function of the most widespread variant, GnRH-II, remains undefined. GnRH-II may affect reproductive behavior; GnRH-II administration to female musk shrews reinstates mating behavior previously inhibited by food restriction. To determine whether this action of GnRH-II is universal, we conducted the following studies in mice. Ovariectomized mice were primed with estradiol benzoate and progesterone once a week and tested for sexual behavior. Females showing a lordosis quotient (LQ) of 50 or higher on the fourth trial underwent food deprivation (FD) for either 24 or 48 h before an additional behavior test. FD for 48 h significantly reduced LQ compared with ad libitum-fed females. Next, females were FD for 48 h or maintained on ad libitum feeding and retested for sexual behavior after an intracerebroventricular infusion of either GnRH-I, GnRH-II, or saline. GnRH-II, but not GnRH-I, significantly increased LQ in FD females compared with FD females treated with saline. Lordosis was unaffected by GnRH-II in females maintained on ad libitum feeding. To assess whether the GnRH-I receptor mediates GnRH-II’s behavioral effects, underfed females were pretreated with the type 1 GnRH receptor antagonist Antide and retested for sexual behavior. Antide pretreatment did not prevent GnRH-II from promoting mating behavior, suggesting that GnRH-II’s behavioral actions are mediated through the type 2 GnRH receptor. We speculate that GnRH-II acts via its own receptor as a regulatory signal in mammals to ensure that reproduction is synchronized with energetically favorable conditions.
Treatment of Vancomycin-Resistant Enterococcus with Quinupristin/Dalfopristin and High-Dose Ampicillin
Authors: Bethea J Audis , Walko Christine M , Targos Patricia A 
Published: April 2004

OBJECTIVE: To report the successful treatment of vancomycin-resistant Enterococcus (VRE) bacteremia using the combination of quinupristin/dalfopristin and high-dose ampicillin. CASE SUMMARY: A 38-year-old African American woman with relapsed acute myeloid leukemia and neutropenic fever developed VRE bacteremia following 3 successive courses of vancomycin for methicillin-resistant staphylococcal infections. Treatment with linezolid was initiated; however, after 9 days of therapy, blood cultures continued to reveal VRE and the patient became febrile. The patient was subsequently switched to quinupristin/dalfopristin and high-dose ampicillin. The fever resolved and all subsequent blood cultures were negative after the initiation of combination therapy. DISCUSSION: The emergence of VRE infections presents a treatment challenge in immunocompromised patients. When treating VRE infections in this patient population, the effectiveness of linezolid and quinupristin/dalfopristin is limited by their bacteriostatic activity when used as monotherapy. Recent in vitro data suggest synergistic activity with quinupristin/dalfopristin when used in combination with other antimicrobials in selected isolates of VRE. CONCLUSIONS: Persistent VRE bacteremia was successfully treated in this neutropenic patient using the combination of high-dose ampicillin and quinupristin/dalfopristin. Case reports and in vitro data suggest that concomitant therapy with high-dose ampicillin may be an effective treatment alternative for VRE infections not responding to standard therapy.
Catalytic Asymmetric Synthesis of Nitroaldols Using a Lanthanum‐Lithium‐BINOL Complex: (2S,3S)‐2‐Nitro‐5‐Phenyl‐1,3‐Pentanediol
Authors: Sasai Hiroaki , Watanabe Shizue , Suzuki Takeyuki , Shibasaki Masakatsu 
Published: April 2004

Abstract

(2S, 3S)‐2‐Nitro‐5‐phenyl‐1, 3‐pentanediol

R 3‐Phenylpropanal

Nitroethanol

P (2S, 3S)‐2‐Nitro‐5‐phenyl‐1, 3‐pentanediol
Palladium‐Catalyzed Amination of Aryl Halides and Aryl Triflates: N‐Hexyl‐2‐Methyl‐4‐Methoxyaniline and N‐Methyl‐N‐(4‐Chlorophenyl)Aniline
Authors: Wolfe John P. , Buchwald Stephen L. 
Published: April 2004

Abstract

N‐Hexyl‐2‐methyl‐4‐methoxylanaline

R 4‐Bromo‐3‐methylanisole

m‐Hexylamine

P N‐Hexyl‐2‐methyl‐4‐methoxylaniline

N‐Methyl‐N‐(4‐chlorophenyl) aniline

R 4‐chlorophenyl trifluoromethanesulfonate

N‐Methylaniline

P N‐Methyl‐N‐(4‐chlorophenyl) aniline