bluuebunny/crossref_metadata_2025 huggingface dataset:
Invertebrate models of drug abuse
Authors: Wolf Fred W. , Heberlein Ulrike
Published: December 2002

Susceptibility to drug addiction depends on genetic and environmental factors and their complex interactions. Studies with mammalian models have identified molecular targets, neurochemical systems, and brain regions that mediate some of the addictive properties of abused drugs. Yet, our understanding of how the primary effects of drugs lead to addiction remains incomplete. Recently, researchers have turned to the invertebrate model systems Drosophila melanogaster and Caenorhabditis elegans to dissect the mechanisms by which abused drugs modulate behavior. Due to their sophisticated genetics, relatively simple anatomy, and their remarkable molecular similarity to mammals, these invertebrate models should provide useful insights into the mechanisms of drug action. Here we review recent behavioral and genetic studies in flies and worms on the effects of ethanol, cocaine, and nicotine, three of the most widely abused drugs in the world. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 161–178, 2003
Behavioral plasticity in C. elegans: Paradigms, circuits, genes
Authors: Hobert Oliver
Published: December 2002

Life in the soil is an intellectual and practical challenge that the nematode Caenorhabditis elegans masters by utilizing 302 neurons. The nervous system assembled by these 302 neurons is capable of executing a variety of behaviors, some of respectable complexity. The simplicity of the nervous system, its thoroughly characterized structure, several sets of well‐defined behaviors, and its genetic amenability combined with its isogenic background make C. elegans an attractive model organism to study the genetics of behavior. This review describes several behavioral plasticity paradigms in C. elegans and their underlying neuronal circuits and then goes on to review the forward genetic analysis that has been undertaken to identify genes involved in the execution of these behaviors. Lastly, the review outlines how reverse genetics and genomic approaches can guide the analysis of the role of genes in behavior and why and how they will complement the forward genetic analysis of behavior. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 203–223, 2003
Neural substrates of memory: From synapse to system
Authors: Dubnau Josh , Chiang Ann‐Shyn , Tully Tim
Published: December 2002

One of the fundamental challenges of modern neuroscience is to understand how memories are acquired, stored, and retrieved by the brain. In the broadest terms, attempts to dissect memory can be broken down into four experimental disciplines: (1) identification of molecular components, (2) ex vivo and in vivo cellular analysis of neuronal function, (3) theoretical modeling approaches of neural systems, and (4) organismal‐level behavioral analyses. Our objective here is to offer a conceptually unifying perspective and to discuss this perspective in relation to an experiment analysis of memory in Drosophila. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 238–253, 2003
Cellular bases of behavioral plasticity: Establishing and modifying synaptic circuits in the Drosophila genetic system
Authors: Rohrbough Jeffrey , O'Dowd Diane K. , Baines Richard A. , Broadie Kendal
Published: December 2002

Genetic malleability and amenability to behavioral assays make Drosophila an attractive model for dissecting the molecular mechanisms of complex behaviors, such as learning and memory. At a cellular level, Drosophila has contributed a wealth of information on the mechanisms regulating membrane excitability and synapse formation, function, and plasticity. Until recently, however, these studies have relied almost exclusively on analyses of the peripheral neuromuscular junction, with a smaller body of work on neurons grown in primary culture. These experimental systems are, by themselves, clearly inadequate for assessing neuronal function at the many levels necessary for an understanding of behavioral regulation. The pressing need is for access to physiologically relevant neuronal circuits as they develop and are modified throughout life. In the past few years, progress has been made in developing experimental approaches to examine functional properties of identified populations of Drosophila central neurons, both in cell culture and in vivo. This review focuses on these exciting developments, which promise to rapidly expand the frontiers of functional cellular neurobiology studies in Drosophila. We discuss here the technical advances that have begun to reveal the excitability and synaptic transmission properties of central neurons in flies, and discuss how these studies promise to substantially increase our understanding of neuronal mechanisms underlying behavioral plasticity. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 254–271, 2003
Modeling α‐helical coiled‐coil interactions: The axial and azimuthal alignment of 1B segments from vimentin intermediate filaments
Authors: Smith Thomasin A. , Hempstead Paul D. , Palliser Christopher C. , Parry David A.D.
Published: December 2002

Attempts at predicting the relative axial alignments of fibrous protein molecules in filamentous structures have relied upon representing the (multichain) molecular structure by a one‐dimensional sequence of amino acids. Potential intermolecular ionic and apolar interactions were counted and determined as a function of the relative axial stagger between the molecules. No attempts were made to consider the azimuthal aspect of the interacting molecules and neither were apolar or ionic energy terms used. Surprisingly, this simple approach proved remarkably informative and yielded accurate predictions of the axial periods present. However, a more comprehensive analysis involving the energetics of aggregation taking due regard for the relative azimuths of the molecules as well as their separation should decrease the noise level in the calculations and reveal other pertinent information. Toward that end, we have modeled the interaction between two α‐helical coiled‐coil segments in intermediate filament molecules (1B segments from human vimentin). The relative axial alignment and polarity of the molecules is already known from detailed crosslinking studies and this provides a criterion against which the success (or otherwise) of the modeling can be judged. The results confirm that an antiparallel alignment of two 1B segments is preferred over any of the parallel options (as observed experimentally). The calculated axial alignment, however, is not identical to that observed from detailed crosslinking studies indicating that other parts of the molecule (probably the head and tail domains as well as other coiled‐coil segments) have a crucial role in determining the precise mode of axial aggregation. The results also show that the apolar interactions seem to be significantly less important in the alignment process than the ionic ones. This is consistent with the observation of a well‐defined period in the linear disposition of the charged (but not apolar) residues along the length of the outer surface of the vimentin molecule. Proteins 2003;50:207–212. © 2002 Wiley‐Liss, Inc.
High‐resolution structure and biochemical properties of a recombinant Proteus mirabilis catalase depleted in iron
Authors: Andreoletti Pierre , Sainz Germaine , Jaquinod Michel , Gagnon Jean , Jouve Hélène Marie
Published: December 2002

Heme catalases are homotetrameric enzymes with a highly conserved complex quaternary structure, and their functional role is still not well understood. Proteus mirabilis catalase (PMC), a heme enzyme belonging to the family of NADPH‐binding catalases, was efficiently overexpressed in E. coli. The recombinant catalase (rec PMC) was deficient in heme with one‐third heme and two‐thirds protoporphyrin IX as determined by mass spectrometry and chemical methods. This ratio was influenced by the expression conditions, but the enzyme‐specific activity calculated relative to the heme content remained unchanged. The crystal structure of rec PMC was solved to a resolution of 2.0 Å, the highest resolution obtained to date with PMC. The overall structure was quite similar to that of wild‐type PMC, and it is surprising that the absence of iron had no effect on the structure of the active site. Met 53 close to the essential His 54 was found less oxidized in rec PMC than in the wild‐type enzyme. An acetate anion was modeled in an anionic pocket, away from the heme group but important for the enzymatic reaction. An alternate conformation observed for Arg 99 could play a role in the formation of the H‐bond network connecting two symmetrical subunits of the tetramer. Proteins 2003;50:261–271. © 2002 Wiley‐Liss, Inc.
BisANS binding to tubulin: Isothermal titration calorimetry and the site‐specific proteolysis reveal the GTP‐induced structural stability of tubulin
Authors: Gupta Suvroma , Chakraborty Shalmali , Poddar Asim , Sarkar Nabanita , Das Kali P. , Bhattacharyya Bhabatarak
Published: December 2002

Interactions of bisANS and ANS to tubulin in the presence and absence of GTP were investigated, and the binding and thermodynamic parameters were determined using isothermal titration calorimetry. Like bisANS binding to tubulin, we observed a large number of lower affinity ANS binding sites (N1 = 1.3, K1 = 3.7 × 105 M−1, N2 = 10.5, K2 = 7 × 104/M−1) in addition to 1–2 higher affinity sites. Although the presence of GTP lowers the bisANS binding to both higher and lower affinity sites (N1 = 4.3, N2 = 11.7 in absence and N1 = 1.8, N2 = 3.6 in presence of GTP), the stoichiometries of both higher and lower affinity sites of ANS remain unaffected in the presence of GTP. BisANS‐induced structural changes on tubulin were studied using site‐specific proteolysis with trypsin and chymotrypsin. Digestion of both α and β tubulin with trypsin and chymotrypsin, respectively, has been found to be very specific in presence of GTP. GTP has dramatic effects on lowering the extent of nonspecific digestion of β tubulin with trypsin and stabilizing the intermediate bands produced from both α and β. BisANS‐treated tubulin is more susceptible to both trypsin and chymotrypsin digestion. At higher bisANS concentration (>20 μM) both α and β tubulins are almost totally digested with enzymes, indicating bisANS‐induced unfolding or destabilization of tubulin structure. Again, the addition of GTP has remarkable effect on lowering the bisANS‐induced enhanced digestion of tubulin as well as stabilizing effect on intermediate bands. These results of isothermal titration calorimetry, proteolysis and the DTNB‐kinetics data clearly established that the addition of GTP makes tubulin compact and rigid and hence the GTP‐induced stabilization of tubulin structure. No such destabilization of tubulin structure has been noticed with ANS, although, like bisANS, ANS possesses a large number of lower affinity binding sites. On the basis of these results, we propose that the unique structure of bisANS, which in absence of GTP can bind tubulin as a bifunctional ligand (through its two ANS moieties), is responsible for the structural changes of tubulin. Proteins 2003;50:283–289. © 2002 Wiley‐Liss, Inc.
Tumour grading from magnetic resonance spectroscopy: a comparison of feature extraction with variable selection
Authors: Huang Y. , Lisboa P. J. G. , El‐Deredy W.
Published: December 2002

Magnetic resonance spectroscopy (MRS) provides a non‐invasive measurement of the biochemistry of living tissue. However, signal variation due to tissue heterogeneity causes considerable mixing between different disease categories, making accurate class assignments difficult. This paper compares a systematic methodology for classifier design using multivariate bayesian variable selection (MBVS), with one based on feature extraction using independent component analysis (ICA). We illustrate the methodology and assess the classification performance using a data set comprising 41 magnetic resonance spectra acquired in vivo from two grades of brain tumour, namely low‐ and medium‐grade astrocytic tumours, labelled astrocytomas (AST), and high‐grade gliomas and glioblastomas labelled glioblastomas (GL). The aim of this study is threefold. First, to describe the application of the alternative methodologies to MRS, then to benchmark their classification performance, and finally to interpret the classification models in terms of biologically relevant signals derived from the spectra. The classification performance is assessed using the bootstrap method and by application to a test sample in a retrospective study. Copyright © 2003 John Wiley & Sons, Ltd.
In vitro bioequivalence testing
Authors: Chow Shein‐Chung , Shao Jun , Wang Hansheng
Published: December 2002

A statistical test is proposed for in vitro bioequivalence testing between drug products such as nasal aerosols and nasal sprays. The proposed test generalizes the one recommended in the FDA 1999 guidance to the situation where replicated observations obtained from each sampled canister or bottle of the drug product are available. The technique developed by Hyslop, Hsuan and Holder is used so that the proposed test is asymptotically accurate. The type I error probability and power of the proposed test are investigated through a simulation study. A method for determining the required sample size to achieve a desired power is also proposed. A numerical example is given for illustration. Copyright © 2003 John Wiley & Sons, Ltd.
Migration of DCE applications into CORBA and SOAP environments
Authors: Fatoohi R. , Jensen D.
Published: December 2002

Legacy applications based on the Distributed Computing Environment (DCE) are subject to several significant limitations. As the development and support of DCE wanes, object‐oriented development becomes more desirable, and transmission over HTTP is established as the preferred protocol over the Internet, DCE application managers and developers are pressed to find extensions and alternatives to DCE. This paper briefly discusses several alternative targets for migration of DCE systems, then proceeds to detail, compare, and contrast two preferred candidates: CORBA and SOAP. Although we have found that developing a general migration solution for legacy DCE applications to CORBA or SOAP to be a non‐trivial, long‐term project, developing specific solutions that are based on a general architecture is feasible. Given a short list of reasonable premises, many DCE applications may be ported to technologies such as CORBA and SOAP. Copyright © 2002 John Wiley & Sons, Ltd.
Decorating tokens to facilitate recognition of ambiguous language constructs
Authors: Malloy Brian A. , Gibbs Tanton H. , Power James F.
Published: December 2002

Software tools are fundamental to the comprehension, analysis, testing and debugging of application systems. A necessary first step in the development of many tools is the construction of a parser front‐end that can recognize the implementation language of the system under development. In this paper, we describe our use of token decoration to facilitate recognition of ambiguous language constructs. We apply our approach to the C++ language since its grammar is replete with ambiguous derivations such as the declaration/expression and template‐declaration/expression ambiguity. We describe our implementation of a parser front‐end for C++, keystone, and we describe our results in decorating tokens for our test suite including the examples from Clause Three of the C++ standard. We are currently exploiting the keystone front‐end to develop a taxonomy for implementation‐based class testing and to reverse‐engineer Unified Modeling Language (UML) class diagrams. Copyright © 2002 John Wiley & Sons, Ltd.
Conjoined twins in a monozygotic triplet pregnancy: Prenatal diagnosis and X‐inactivation
Authors: Zeng She Min , Yankowitz Jerome , Murray Jeffrey C.
Published: December 2002

Background

The etiology of monozygotic twinning is not known. Some investigators have implicated abnormal X‐inactivation, which could also be related to the increased female:male ratio in higher order multiple gestations in general, and in monozygotic and conjoined twins (CTS) in particular. CTS are rare, and even more unusual when part of a triplet pregnancy.

Methods

DNA polymorphism analysis using 13 markers in the buccal cells of the triplets and the lymphocytes of the parents were used to evaluate zygosity. We investigated the X‐inactivation pattern of the triplets by analyzing methylation at the androgen receptor gene.

Results

We found a female triplet gestation consisting of CTS and a normal singleton. The thoracopagus CTS were joined from the clavicles to the umbilicus. Congenital heart disease was suspected antenatally, but the precise delineation of the heart defects required extensive postnatal evaluation. There was a single placental mass with a thin dividing membrane. Cesarean section was carried out at 32 weeks after the onset of labor. Histologically, the placenta was diamniotic monochorionic. The normal singleton did well after delivery; the CTS died at 35 days from cardiopulmonary collapse. The babies were monozygotic (>99.99% probability). Each baby in this triplet set exhibited a random and symmetric X‐inactivation pattern. The degree of X‐inactivation skewing fell in the range of 50–65%.

Conclusion

Genetic or environmental factors other than abnormal X‐inactivation must be involved in causing monozygous multiple gestation or CTS. Despite prenatal diagnosis, shared myocardium or cardiac anomalies in CTS often determine the prognosis. Teratology 66:278–281, 2002. © 2002 Wiley‐Liss, Inc.
Effect of sera from women with systemic lupus erythematosus or antiphospholipid syndrome and recurrent abortions on human placental explants in culture
Authors: Yacobi Sarah , Ornoy Asher , Blumenfeld Zeev , Miller Richard K.
Published: December 2002

Background

Systemic lupus erythematosus (SLE) with or without evidence of antiphospholipid antibodies (aPA) and antiphospholipid syndrome (APS) is associated with a high rate of spontaneous abortions. The placenta is thought to be the site of pathological damage in many of these abortions. To test this hypothesis, we studied the effects of sera obtained from women with SLE with or without treatment on human placental explants in culture.

Methods

We cultured 5.5‐ to 7.5‐week‐old human placental explants in a culture medium containing F‐12 DMEM and 10% FCS or in 90% human serum obtained from nonpregnant women with SLE prior to or after treatment. Culture was carried out for 96 hr. At the end of the culture period, we studied the secretion of the placental hormones estrogen (E2), progesterone (PGN), and human chorionic gonadotropin (hCG). In addition, we studied the proliferation rate (using PCNA staining) and the rate of apoptosis (using ApoTag) of the trophoblastic cells.

Results

Placentae grew better in normal human serum than in a chemically defined medium of F‐12 DMEM and 10% FCS. Enhanced growth and higher secretion rates for hCG and estradiol (E2) were manifested in placentae cultured in control sera with no change in PGN secretion. Secretion rates of hCG and PGN (but not of E2in the treated group) by placental explants were similar to that of controls. However, the serum levels prior to culture were not measured. Further, explants in serum from untreated women with SLE produced a significant decrease in the proliferation rate of the trophoblastic cells and an increase of apoptosis. Treatment significantly reduced the apoptotic rate and increased cell proliferation, but the cell proliferation rate was still lower than that noted in controls.

Conclusions

We conclude that sera from women with SLE may directly damage the developing placenta reducing proliferation and enhancing apoptosis. Successful treatment of the women reduces that damage. Teratology 66:300–308, 2002. © 2002 Wiley‐Liss, Inc.
Response of groundwater systems in the Dead Sea Rift Valley to the Nuweiba earthquake: Changes in head, water chemistry, and near‐surface effects
Authors: Yechieli Yoseph , Bein Amos
Published: December 2002

The Nuweiba earthquake (Mw = 7.1) of November 1995 had significant effects on groundwater heads, spring discharge, and chemistry in the Dead Sea Rift Valley. Groundwater heads increased by 6 cm near the Dead Sea (local shallow alluvial aquifer) and by 50 cm near the sea of Galilee (regional deep confined aquifer), some 330 and 460 km north of the epicenter, respectively. In the arid central Arava valley, some 210 km north of the epicenter, the discharge of small springs increased significantly. The increase in spring discharge, as recorded in Moa spring, was accompanied by a marked change in its chemistry. However, while the change in discharge followed the earthquake, the chemistry change was found some 16 days before the earthquake. The effect of the earthquake in Moa was enhanced and prolonged because of a breach in the confinement system of the shallow artesian aquifer and the formation of new flow paths along faults, cracks, and dikes. Due to the extreme aridity of the region, the sequence above the aquifer is loaded with soluble salts. Dissolution of these salts by the ascending groundwater accounts for the observed increase in salinity and changes in the spring chemistry with time. Initially, the ascending water flushed the newly formed flow paths, gradually leaching the available soluble salts. Later, as discharge shrank, upward flow was maintained within the already flushed system, and the water chemistry returned to the original aquifer composition.
Climate from borehole data: Energy fluxes and temperatures since 1500
Authors: Beltrami Hugo
Published: December 2002

Variations in the Earth's surface energy balance are recorded in the ground as perturbations of the subsurface thermal regime. Here I apply singular value decomposition (SVD) inversion methods to 826 temperature‐depth profiles distributed world wide, in order to reconstruct ground surface temperature histories (GSTH) and surface heat flux histories (SHFH) from the temperature and heat flux anomalies detected in the shallow subsurface. Inversions yielded a mean ground surface temperature and surface heat flux histories for the Earth's continents for the last 500 years. Results indicate that the global average ground temperature and ground heat flux have increased an average of 0.45°K and 18.0 mWm2 respectively over the last 200 years, and 0.9°K in the last five centuries.
TEMPERATURE DEPENDENCE OF PHOTOLUMINESCENCE OF FLAT AND UNDULATED SiGe/Si MULTIPLE QUANTUM WELLS
Authors: CHENG B. W. , ZHANG J. G. , ZUO Y. H. , MAO R. W. , HUANG C. J. , LUO L. P. , YAO F. , WANG Q. M.
Published: December 2002

Photoluminescence (PL) of strained SiGe/Si multiple quantum wells (MQW) with flat and undulated SiGe well layers was studied at different temperature. With elevated temperature from 10K, the no-phonon (NP) peak of the SiGe layers in the flat samples has firstly a blue shift due to the dominant transition converting from bound excitons (BE) to free excitons (FE), and then has a red shift when the temperature is higher than 30K because of the narrowing of the band gap. In the undulated sample, however, monotonous blue shift was observed as the temperature was elevated from 10 K to 287 K. The thermally activated electrons, confined in Si due to type-II band alignment, leak into the SiGe crest regions, and the leakage is enhanced with the elevated temperature. It results in a blue shift of the SiGe luminescence spectra.
GROWTH AND CHARACTERIZATION OF C-ORIENTED LiNbO3 THIN FILMS ON Si (100) BY PLD
Authors: WANG XINCHANG , YE ZHIZHEN , HE JUNHUI , HUANG JINGYUN , ZHAO BINGHUI
Published: December 2002

Lithium niobate ( LiNbO 3) thin film is an important material for optical waveguide. Recently, particular attention has been paid to the application of LiNbO 3 (LN) thin films. To develop and fabricate integrated optical devices, the growth of thin LN epitaxial films onto silicon substrate is of great importance and particularly attractive. In this paper, LN thin film was grown by pulsed laser deposition (PLD). Stoichiometric LN ceramic is used as a target. Amorphous SiO 2 buffer layer was coated on Si (100) wafer by in-situ themal oxidation before the deposition. The optimized condition of growing LN film on Si (100) by PLD is found: O 2 pressure 30 Pa, substrate temperature 600°C. Only (006) reflection of LN was observed besides the (002) reflection of silicon substrate from XRD pattern. The FWHM (~0.21°) of (006) reflection peak is much narrower than the value reported by Lee [1]. The results of XRD measurement indicate that the LN film was epitaxially grown along the c-axis. Transmission electron microcopy (TEM) patterns confirm that the film has superior crystalline quality. The optical waveguiding properties of the films were demonstrated by a prism coupler method. Fully c-oriented thin film could be grown on silicon substrate by PLD without the buffer layer and the induced electric field.
STUDY OF THE ELECTRICAL PROPERTIES OF SOL-GEL-DERIVED TITANIUM-VANADIUM OXIDE FILMS
Authors: ZHAO GAOLING , HAN GAORONG
Published: December 2002

Titanium-vanadium oxide films were prepared by the sol-gel method. The effects of vanadium incorporation on the crystallization behavior TiO 2 were investigated by X-ray diffraction analysis. The results showed that anatase and rutile type solid solution Ti 1-x V x O 2 films were obtained for x < 0.15 and x > 0.15 samples, respectively. Anatase and V 2 O 5 were found in x = 0.15 sample. Moreover, it was found that the crystallization of the film increased with increasing amount of vanadium. The electrical properties of Ti 1-x V x O 2 films were studied by measuring their resistance and Hall mobility. It was revealed that the resistivity of Ti 1-x V x O 2 films decreased with increasing x when the solid solution was formed, while the resistivity increased when the crystallization of vanadium oxide precipitated. The Hall constant was negative, indicating that Titanium-vanadium oxide is an n-type semiconductor. The evolution of the resistance and Hall mobility was ascribed to the 3d electrons of vanadium.
Clinical Characteristics and Outcomes From an Institutional Series of Acinar Cell Carcinoma of the Pancreas and Related Tumors
Authors: Holen Kyle D. , Klimstra David S. , Hummer Amanda , Gonen Mithat , Conlon Kevin , Brennan Murray , Saltz Leonard B.
Published: December 2002

PURPOSE: Acinar cell carcinoma is a rare tumor of the exocrine pancreas. Clinical features such as prognostic information, survival, and treatment outcomes are unknown. We present the largest retrospective review to date.

PATIENTS AND METHODS: Thirty-nine patients with pathologically confirmed acinar neoplasms of the pancreas were identified between August 1981 and January 2001. Demographic data, tumor characteristics, and treatment information were obtained by chart review. Survival probabilities were estimated by using the Kaplan-Meier method and compared using the log-rank test.

RESULTS: The median survival for all patients was 19 months. On the basis of a univariate analysis, the patients’ stage of disease correlated significantly with survival. The median survival of patients with localized disease was 38 months, versus 14 months for those presenting with metastases (P = 0.03). Patients who could be treated with surgery as first-line therapy had a longer survival time (36 months) compared with those who did not have surgery (14 months). Two of 18 patients who received chemotherapy and three of eight patients who received radiation had a major response.

CONCLUSION: The survival curves suggest a more aggressive cancer than pancreatic endocrine neoplasms but one that is less aggressive than ductal adenocarcinoma of the pancreas. Those patients who present with localized disease have a much better prognosis than those who present with metastases. There is a high recurrence rate after complete surgical resection, suggesting that micrometastases are present even in localized disease and that adjuvant therapies may be indicated. Chemotherapy and radiation afford disappointing results, however, and novel therapies are needed.
Model of Chemotherapy-Induced Myelosuppression With Parameter Consistency Across Drugs
Authors: Friberg Lena E. , Henningsson Anja , Maas Hugo , Nguyen Laurent , Karlsson Mats O.
Published: December 2002

PURPOSE: To develop a semimechanistic pharmacokinetic-pharmacodynamic model describing chemotherapy-induced myelosuppression through drug-specific parameters and system-related parameters, which are common to all drugs.

PATIENTS AND METHODS: Patient leukocyte and neutrophil data after administration of docetaxel, paclitaxel, and etoposide were used to develop the model, which was also applied to myelosuppression data from 2′-deoxy-2′-methylidenecytidine (DMDC), irinotecan (CPT-11), and vinflunine administrations. The model consisted of a proliferating compartment that was sensitive to drugs, three transit compartments that represented maturation, and a compartment of circulating blood cells. Three system-related parameters were estimated: baseline, mean transit time, and a feedback parameter. Drug concentration-time profiles affected the proliferation of sensitive cells by either an inhibitory linear model or an inhibitory Emax model. To evaluate the model, system-related parameters were fixed to the same values for all drugs, which were based on the results from the estimations, and only drug-specific parameters were estimated. All modeling was performed using NONMEM software.

RESULTS: For all investigated drugs, the model successfully described myelosuppression. Consecutive courses and different schedules of administration were also well characterized. Similar system-related parameter estimates were obtained for the different drugs and also for leukocytes compared with neutrophils. In addition, when system-related parameters were fixed, the model well characterized chemotherapy-induced myelosuppression for the different drugs.

CONCLUSION: This model predicted myelosuppression after administration of one of several different chemotherapeutic drugs. In addition, with fixed system-related parameters to proposed values, and only drug-related parameters estimated, myelosuppression can be predicted. We propose that this model can be a useful tool in the development of anticancer drugs and therapies.
Multidisciplinary Systems Approach to Chemotherapy Safety: Rebuilding Processes and Holding the Gains
Authors: Womer Richard B. , Tracy Ellen , Soo-Hoo Winson , Bickert Betsy , DiTaranto Susan , Barnsteiner Jane H.
Published: December 2002

PURPOSE: The problem of medication safety came to public attention largely through a chemotherapy error, and the high toxicity and low therapeutic index of anticancer medications make safety in their prescription and administration critical. We have undertaken a thorough revision of our systems for inpatient chemotherapy.

METHODS: We participated in a multi-institutional collaborative effort of the Institute for Healthcare Improvement, and used their rapid cycle change method. Particularly powerful systems change concepts were driving out fear, “trapping” errors and learning from them, focusing on outcome rather than on input, simplifying and standardizing, using constraints and “forcing functions,” reducing handoffs, and paying attention to human factors.

RESULTS: Applying these concepts to our chemotherapy delivery system, we have achieved an 84% decrease in the number of chemotherapy errors that actually reach patients per 1,000 chemotherapy doses, and have sustained that improvement for 5 years.

CONCLUSION: Factors contributing to our success include the rapid cycle change method, strong support from hospital administration, grassroots participation, and a tradition of interdisciplinary cooperation. Computerized direct physician order entry and cooperative group participation have had mixed effects. Continued efforts at improvement have been key to holding our gains. Although specific problems and changes may not be relevant to other organizations, the concepts and methods we used are generally applicable.
Goserelin Versus Cyclophosphamide, Methotrexate, and Fluorouracil as Adjuvant Therapy in Premenopausal Patients With Node-Positive Breast Cancer: The Zoladex Early Breast Cancer Research Association Study
Authors: Jonat W. , Kaufmann M. , Sauerbrei W. , Blamey R. , Cuzick J. , Namer M. , Fogelman I. , de Haes J. C. , de Matteis A. , Stewart A. , Eiermann W. , Szakolczai I. , Palmer M. , Schumacher M. , Geberth M. , Lisboa B.
Published: December 2002

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause.

PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer.

RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P = .0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group.

CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.
Population-Based Assessment of Hospitalizations for Toxicity From Chemotherapy in Older Women With Breast Cancer
Authors: Du Xianglin L. , Osborne Cynthia , Goodwin James S.
Published: December 2002

PURPOSE: There are no population-based data on hospitalization rate for toxicity from breast cancer chemotherapy, and even large clinical trials often do not report this information. Medicare data, linked to the Surveillance, Epidemiology, and End-Results (SEER) tumor registries, are now used to assess rates of hospitalization for chemotherapy-related toxicity in a population-based setting.

PATIENTS AND METHODS: A total of 35,060 women diagnosed with stages I through IV breast cancer aged ≥ 65 from 1991 through 1996 were identified from the SEER-Medicare linked program and studied. Patients were defined as being hospitalized for adverse effects of chemotherapy if there was a Medicare inpatient claim for neutropenia, fever, thrombocytopenia, or adverse effect of systemic therapy less than 7 months after diagnosis of breast cancer.

RESULTS: More than 9% of women with breast cancer who received chemotherapy were admitted with the diagnosis of neutropenia, fever, thrombocytopenia, or adverse effect of systemic therapy, compared with 0.5% of women with breast cancer who did not receive chemotherapy. The rates for stage I to IV were 6.3%, 8.1%, 12.3%, and 13.2% in those treated with chemotherapy, and 0.4%, 0.6%, 0.7%, and 1.5% in women not treated with chemotherapy. The hospitalization rates for adverse effects increased significantly with comorbidity score and varied more than two-fold across the nine SEER areas but did not vary by age. Use of anthracycline-containing chemotherapy agents was associated with greater odds of these toxicities (eg, odds ratio, 2.53 for neutropenia; 95% confidence interval, 1.97 to 3.26).

CONCLUSION: This study demonstrated the feasibility of using Medicare data to assess rates of hospitalization for serious toxicity associated with cancer chemotherapy. Rates in actual practice were higher than those reported in clinical trials and did not vary by age.
Temozolomide in Malignant Gliomas of Childhood: A United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study
Authors: Lashford L. S. , Thiesse P. , Jouvet A. , Jaspan T. , Couanet D. , Griffiths P. D. , Doz F. , Ironside J. , Robson K. , Hobson R. , Dugan M. , Pearson A. D.J. , Vassal G. , Frappaz D.
Published: December 2002

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide.

PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m2 on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans.

RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication.

CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.
Responsiveness of Subjective and Objective Measures of Pain and Function Following Operative Interventions for Musculoskeletal Conditions: A Narrative Review
Authors: Waddell Lily M. , Musbahi Omar , Collins Jamie E. , Jones Morgan H. , Selzer Faith , Losina Elena , Katz Jeffrey N.
Published: January 2024

Objective

Musculoskeletal (MSK) disorders affect ~50% of US adults and 75% of those over the age of 65, representing a sizable economic and disability burden. Outcome measures, both objective and subjective, help clinicians and investigators determine whether interventions to treat MSK conditions are effective. This narrative review qualitatively compared the responsiveness of different types of outcome measures, a key measurement characteristic that assesses an outcome measure's ability to detect change in patient status.

Methods

We evaluated elective orthopedic interventions as a model for assessing responsiveness because the great majority of patients improves following surgery. We searched for articles reporting responsiveness (quantified as effect size [ES]) of subjective and objective outcome measures after orthopedic surgery and included 16 articles reporting 17 interventions in this review.

Results

In 14 of 17 interventions, subjective function measures had an ES 10% greater than that of objective function measures. Two reported a difference in ES of <10%. The sole intervention that demonstrated higher ES of objective function used a composite measure. Sixteen interventions reported measures of subjective pain and/or mixed measures and subjective function. In nine interventions, subjective pain had a higher ES than subjective function by >10%, in three, subjective function had a higher ES than subjective pain by >10%, and in the remaining four, the difference between pain and function was <10%.

Conclusion

These findings reinforce the clinical observation that subjective pain generally changes more than function following elective orthopedic surgery. They also suggest that subjective function measures are more responsive than objective function measures, and composite scores may be more responsive than individual performance tests.
Superior Durability and Activity of a Benchmark Triple‐Conducting Cathode by Tuning Thermo‐Mechanical Compatibility for Protonic Ceramic Fuel Cells
Authors: Yu Zhexiang , Ge Lin , Ni Qing , Zheng Yifeng , Chen Han , Zhou Xingkai , Mi Yaowei , Shi Bochang , Yu Xiaole , Wu Bangze , Bi Lei , Zhu Yunfeng
Published: January 2024

As a benchmark triple‐conducting cathode, BaCo0.4Fe0.4Zr0.1Y0.1O3−δ (BCFZY) has been widely investigated for protonic ceramic fuel cells (PCFC) in recent years. However, the reported electrochemical performance of BCFZY cathode differs, which is determined in this work to originate from the thermal expansion mismatch between BCFZY and electrolyte. Accordingly, two strategies for enhanced thermo‐mechanical compatibility are examined: impregnation and thermal expansion offset. In contrast to the impregnation of BCFZY nanoparticles on electrolyte backbones that only helps improve electrochemical performance, negative thermal expansion oxide Sm0.85Cu0.15MnO3−δ (SCM)‐offset BCFZY exhibits superior durability and activity simultaneously. Specifically, the polarization resistance decay rate of the SCM‐offset BCFZY is only ~0.2%/100 h, compared with ~18.75%/100 h for “impregnated BCFZY.” Moreover, pure SCM generates moderate cathodic performance (area‐specific resistance = 0.11 Ω cm2, 700 °C), X‐ray diffraction and transmission electron microscopy reveal an in‐situ formed intergranular Ba2Cu3SmO7−δ phase at the boundaries of BCFZY and SCM. Thus, SCM can serve as a “three‐effect” additive, i) offset thermo‐expansion, ii) strengthen electrode structure and adhesion, and iii) provide acceptable oxygen‐reduction‐reaction activity, being favorable for superior performance. A PCFC using a SCM‐offset BCFZY cathode achieves the highest power density (1455 mW cm−2) yet recorded for PCFCs with BCFZY‐based cathodes.
Tailoring Addition Sequence of Metal Ions in Precursor Solution Drives Highly Efficient Kesterite Solar Cells
Authors: Zhou Qing , Sun Yali , Li Hao , Sun Yuzhou , Zhao Wei , Liang Baolai , Wang Ying , Ma Yujiao , Zhao Liang , Teng Xiaoyun , Gao Chao , Yu Wei
Published: January 2024

The unsatisfactory material quality of absorber is an important factor limiting the development of Cu2ZnSn(S,Se)4 (CZTSSe) thin‐film solar cells, including poor crystallization, multi‐layer structure, and various defects. Here, an effective strategy to enhance the quality of kesterite absorber and improve the performance of solar cells is proposed by tailoring the additional sequence of metal ions in precursor solution. With an addition sequence S─Sn─Cu─Zn (STCZ), higher values of Cu+/Cu2+ and Sn4+/Sn2+ ratios are obtained, and the surface grain growth is modulated into an inclined growth mode. Consequently, the decomposition of CZTSSe bulk is suppressed and its final morphology presents mainly as large grains spanning across the absorber. The quality of absorber and its interface is enhanced with activating the desirable shallow acceptor and reducing recombination center defects. An encouraging efficiency of over 12% for CZTSSe solar cells with increased short‐circuit current density and fill factor is realized. This novel strategy provides insight into crystallization mechanism of kesterite photovoltaic material and has guiding significance for further improving material crystallization and absorber quality.
Deshielding Anions Enable Solvation Chemistry Control of LiPF6‐Based Electrolyte toward Low‐Temperature Lithium‐Ion Batteries
Authors: Yuan Song , Cao Shengkai , Chen Xi , Wei Jiaqi , Lv Zhisheng , Xia Huarong , Li Jiaofu , Zhang Hang , Liu Lin , Tian Changhao , Chen Lixun , Zhang Wei , Xing Zhenxiang , Li Haicheng , Li Shuzhou , Zhu Qiang , Feng Xue , Chen Xiaodong
Published: January 2024

Severe capacity decay under subzero temperatures remains a significant challenge for lithium‐ion batteries (LIBs) due to the sluggish interfacial kinetics. Current efforts to mitigate this deteriorating interfacial behavior rely on high‐solubility lithium salts (e.g., Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), Lithium bis(fluorosulfonyl)imide (LiFSI))‐based electrolytes to construct anion participated solvation structures. However, such electrolytes bring issues of corrosion on the current collector and increased costs. Herein, the most commonly used Lithium hexafluorophosphate (LiPF6) instead, to establish a peculiar solvation structure with a high ratio of ion pairs and aggregates by introducing a deshielding NO3− additive for low‐temperature LIBs is utilized. The deshielding anion significantly reduces the energy barrier for interfacial behavior at low temperatures. Benefiting from this, the graphite (Gr) anode retains a high capacity of ≈72.3% at −20 °C, which is far superior to the 32.3% and 19.4% capacity retention of counterpart electrolytes. Moreover, the LiCoO2/Gr full cell exhibits a stable cycling performance of 100 cycles at −20 °C due to the inhibited lithium plating. This work heralds a new paradigm in LiPF6‐based electrolyte design for LIBs operating at subzero temperatures.
Using Paper as a Biomimetic Fog Harvesting Material
Authors: Breuer Carina , Cordt Cynthia , Hiller Benjamin , Geissler Andreas , Biesalski Markus
Published: January 2024

This study identifies important factors for designing an effective biomimetic paper‐based fog harvesting substrate by examining the harvesting properties of different surfaces, including glass, polyethylene, and superhydrophobic paper. In laboratory‐scale fogging tests, the wetting behavior of the substrates is characterized, and the importance of the tilt angle of the respective surface relative to the fog flow is elaborated. Because successful fog harvesting requires both efficient accumulation of water droplets on the surface (by condensation and collision) and sufficient but not excessive roll‐off of the liquid, the amount of water finally collected is clearly related to the pinning effect, which should prevent the smallest droplets from being carried away by the wind but must not lead to full and permanent wetting of the surface. Coalescence is identified as a major phenomenon to improve droplet roll‐off. In this context, superhydrophobic paper indicates to be a more effective water collector than glass or polyethylene, especially when oriented vertically, since it allows the droplets to roll off very efficiently. Finally, the addition of glass particles to the superhydrophobic coating is proposed as a means of enhancing pinning and improving the fog harvesting efficiency.