bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping Responses of Emergency Physicians and Nurses to the 2003 Severe Acute Respiratory Syndrome Outbreak
Authors: Phua D.H. , Tang H.K. , Tham K.Y.
Published: April 2005

Objectives: During the 2003 severe acute respiratory syndrome (SARS) outbreak, health care workers (HCWs) experienced unusual stressors. The study hospital introduced psychosocial interventions to help HCWs. This study aimed to examine the coping strategies adopted by the emergency department (ED) HCWs who cared for the SARS patients. Methods: In November 2003, a self‐administered questionnaire of physicians and nurses was conducted in the hospital ED that is the national SARS screening center in Singapore. Data collected included demographics and responses to these instruments: 1) the Coping Orientation to Problems Experienced (COPE) to assess coping strategies, 2) the Impact of Event Scale (IES) to measure psychological reactions, and 3) the General Health Questionnaire 28 (GHQ 28) to measure psychiatric morbidity. Results: Thirty‐eight of 41 (92.7%) physicians and 58 of 83 (69.9%) nurses responded. The respondents reported a preference for problem‐focused and emotion‐focused coping measures. The physicians chose humor as a coping response significantly more frequently (p < 0.001) than nurses, scoring 9.61/16 (95% CI = 8.52 to 10.69), compared with the nurses' score of 7.05/16 (95% CI = 6.28 to 7.83). The Filipino HCWs turned to religion as a coping response significantly more frequently (p < 0.001) than the non‐Filipino HCWs, scoring 14.38/16 (95% CI = 13.33 to 15.42), compared with 9.93/16 (95% CI = 9.00 to 10.87) for the non‐Filipinos. Psychiatric morbidity was 17.7% on the IES and 18.8% on the GHQ 28, with the trend for physicians to report lower psychiatric morbidity. Conclusions: With a supportive hospital environment, ED HCWs chose adaptive coping in response to the outbreak and reported low psychiatric morbidity. Physicians chose humor and Filipinos chose turning to religion as their preferred responses. Psychosocial interventions to help HCWs need to take these preferences into account.
Advanced Statistics: Bootstrapping Confidence Intervals for Statistics with “Difficult” Distributions
Authors: Haukoos Jason S. , Lewis Roger J.
Published: April 2005

The use of confidence intervals in reporting results of research has increased dramatically and is now required or highly recommended by editors of many scientific journals. Many resources describe methods for computing confidence intervals for statistics with mathematically simple distributions. Computing confidence intervals for descriptive statistics with distributions that are difficult to represent mathematically is more challenging. The bootstrap is a computationally intensive statistical technique that allows the researcher to make inferences from data without making strong distributional assumptions about the data or the statistic being calculated. This allows the researcher to estimate confidence intervals for statistics that do not have simple sampling distributions (e.g., the median). The purposes of this article are to describe the concept of bootstrapping, to demonstrate how to estimate confidence intervals for the median and the Spearman rank correlation coefficient for non‐normally‐distributed data from a recent clinical study using two commonly used statistical software packages (SAS and Stata), and to discuss specific limitations of the bootstrap.
Comparison of Oxycodone and Hydrocodone for the Treatment of Acute Pain Associated with Fractures: A Double‐blind, Randomized, Controlled Trial
Authors: Marco Catherine A. , Plewa Michael C. , Buderer Nancy , Black Cheryl , Roberts Alisa
Published: April 2005

Background: Previous studies have demonstrated the efficacy of oxycodone and hydrocodone for the treatment of acute pain. However, to the best of the authors' knowledge, no previous reports have compared the efficacies of these commonly prescribed agents. Objectives: To compare the efficacies of oxycodone and hydrocodone for the treatment of acute pain associated with fractures in emergency department (ED) patients. Methods: This prospective, double‐blind, randomized, controlled trial was conducted at an urban trauma center with an annual census of 65,000. Eligible participants included ED patients over the age of 12 years with fractures who consented to participate. Subjects were randomized to receive either oxycodone (5 mg orally [po]) with acetaminophen, or hydrocodone (5 mg po) with acetaminophen. Measurements included demographic information; pain scores on a verbal numeric rating scale at baseline and at 30 and 60 minutes; vital signs at baseline and at 30 and 60 minutes; and adverse effects. Ninety‐five‐percent confidence intervals (95% CIs) constructed about means and proportions were used to assess differences between the oxycodone and hydrocodone groups in analgesic efficacy and side effects. Results: Seventy‐three subjects were randomized to receive oxycodone or hydrocodone. Sixty‐seven subjects completed the ED study period (n= 35, oxycodone; n= 32, hydrocodone). There was no difference between the two groups in age, weight, gender, ethnicity, diagnoses, baseline pain scores, or vital signs. Patients in both groups had pain relief from baseline to 30 minutes (oxycodone mean change 3.7, 95% CI = 2.9 to 4.6; hydrocodone mean change 2.5, 95% CI = 1.7 to 3.3), and from baseline to 60 minutes (oxycodone mean change 4.4, 95% CI = 3.2 to 5.6; hydrocodone mean change 3.0, 95% CI = 2.1 to 3.9). There was no difference in pain between the patients treated with oxycodone and hydrocodone at 30 minutes (mean difference between groups −0.6, 95% CI =−1.8 to 0.5) or at 60 minutes (mean difference −0.5, 95% CI =−2.0 to 1.0). There was no difference between the groups in nausea, vomiting, itching, or drowsiness; however, the hydrocodone patients had a higher incidence of constipation (oxycodone 0%, hydrocodone 21%, difference in proportions 21%, 95% CI = 3% to 39% more with hydrocodone). Conclusions: Treatment with acetaminophen and either oxycodone, 5 mg po, or hydrocodone, 5 mg po, resulted in pain relief among ED patients with acute fractures, and there was no difference between the two agents at 30 and 60 minutes. Adverse effect profiles were similar, with the exception of a higher incidence of subsequent constipation with the use of hydrocodone. These results suggest that oxycodone and hydrocodone have similarly potent analgesic effects in the first hour of treatment for ED patients with acute fractures.
Growth Hormone Modulates Thymocyte Development in Vivo through a Combined Action of Laminin and CXC Chemokine Ligand 12
Authors: Smaniotto Salete , de Mello-Coelho Valéria , Villa-Verde Déa Maria Serra , Pléau Jean-Marie , Postel-Vinay Marie-Catherine , Dardenne Mireille , Savino Wilson
Published: April 2005

Previous evidence indicates that GH modulates thymic cell migration. In this study we approached this issue in vivo, studying thymocyte migration in GH transgenic animals and in normal mice treated intrathymically with GH. Extracellular matrix and chemokines are involved in thymocyte migration. In this respect, thymocyte adhesion to laminin was higher in GH-treated animals than controls, and the numbers of migrating cells in laminin-coated Transwells was higher in GH-transgenic and GH-injected mice. Additionally, CXC chemokine ligand 12 (CXCL12)-driven migration was higher in GH-Tg and GH-treated animals compared with controls. Interestingly, although CXCR4 expression on thymocytes did not change in GH-Tg mice, the CXCL12 intrathymic contents were higher. We found that CXCL12, in conjunction with laminin, would additionally enhance the migration of thymocytes previously exposed to high concentrations of GH in vivo. Lastly, there was an augmentation of recent thymic emigrants in lymph nodes from GH-Tg and GH-injected animals. In conclusion, enhanced thymocyte migration in GH transgenic mice as well as GH-injected mice results at least partially from a combined action of laminin and CXCL12. Considering that GH is presently being used as an adjuvant therapeutic agent in immunodeficiencies, including AIDS, the concepts defined herein provide important background knowledge for future GH-based immune interventions.
Enhancement of Tumor Necrosis Factor-α-Induced Growth Inhibition by Insulin-Like Growth Factor-Binding Protein-5 (IGFBP-5), But Not IGFBP-3 in Human Breast Cancer Cells
Authors: Butt Alison J. , Dickson Kristie A. , Jambazov Stan , Baxter Robert C.
Published: April 2005

Expression of IGF-binding protein-3 (IGFBP-3) and IGFBP-5 in human breast cancer cells induces apoptosis and is associated with modulations in Bcl-2 proteins, suggesting that these IGFBPs induce an intrinsic apoptotic pathway. In this study we demonstrate that although both IGFBPs induced the activation of caspase-8 and caspase-9, the expression of IGFBP-5, but not IGFBP-3, sensitized MDA-MB-231 breast cancer cells to the inhibitory effects of TNFα. This sensitivity to TNFα was associated with a block in nuclear factor-κB-mediated cell survival signals. IGFBP-5 expression was also associated with a caspase-8-independent activation of Bid, increased levels of cytosolic second mitochondria-derived activator of caspase (Smac)/direct inhibitor of apoptosis proteins (IAP) binding protein with low pI (DIABLO), and an enhanced phosphorylation of c-Jun N-terminal kinase, both basally and in response to TNFα. These results suggest that IGFBP-5 expression may influence extrinsic apoptotic pathways via a differential modulation of downstream cell survival and cell death pathways. Furthermore, although IGFBP-3 and IGFBP-5 share much structural and functional homology, they can modulate distinct apoptotic pathways in human breast cancer cells.
Differential Adaptive Responses to Chronic Stress of Maternally Stressed Male Mice Offspring
Authors: Chung Sooyoung , Son Gi Hoon , Park Sung Ho , Park Eonyoung , Lee Kun Ho , Geum Dongho , Kim Kyungjin
Published: April 2005

It is well established that stress in early life can alter the activity of the hypothalamus-pituitary-adrenal (HPA) axis, but most studies to date have focused on HPA reactivity in response to a single acute stress. The present study addressed whether stress in pregnant mice could influence the adaptive responses of their offspring to chronic stress. Male offspring were exclusively used in this study. Elevated plus maze tests revealed that 14 d of repeated restraint stress (6 h per day; from postnatal d 50–63) significantly increased anxiety-like behavior in maternally stressed mice. NBI 27914, a CRH receptor antagonist, completely eliminated anxiety-related behaviors in a dose-dependent manner, indicating an involvement of a hyperactive CRH system. In accordance with increased anxiety, CRH contents in the hypothalamus and amygdala were significantly higher in these mice. Despite an increased basal activity of the CRH-ACTH system, the combination of chronic prenatal and postnatal stress resulted in a significant reduction of basal plasma corticosterone level, presumably because of a defect in adrenal function. Along with alterations in hypothalamic and hippocampal corticosteroid receptors, it was also demonstrated that a dysfunction in negative feedback inhibition of the HPA axis could be deteriorated by chronic stress in maternally stressed male mice. Taken together, these results indicate that exposure to maternal stress in the womb can affect an animal’s coping capacity to chronic postnatal stress.
Adrenocorticotropin Evokes Transient Elevations in Intracellular Free Calcium ([Ca2+]i) and Increases Basal [Ca2+]i in Resting Chondrocytes through a Phospholipase C-Dependent Mechanism
Authors: Evans Jodi F. , Shen Chwan-L , Pollack Simcha , Aloia John F. , Yeh James K.
Published: April 2005

Both clinical and in vitro evidence points to the involvement of the melanocortin peptide, ACTH, in the terminal differentiation of chondrocytes. Terminal differentiation along the endochondral pathway is responsible for linear growth, but also plays a role in osteoarthritic cartilage degeneration. Chondrocyte terminal differentiation is associated with an incremental increase in chondrocyte basal intracellular free calcium ([Ca2+]i), and ACTH agonism of melanocortin receptors is known to mobilize [Ca2+]i. Using differentiated resting chondrocytes highly expressing type II collagen and aggrecan, we examined the influence of both ACTH and dexamethasone treatment on matrix gene transcription and [Ca2+]i. Resting chondrocytes treated concurrently with dexamethasone and ACTH expressed matrix gene transcripts in a pattern consistent with that of rapid terminal differentiation. Using the fluorescent Ca2+ indicator, fura-2, we determined that ACTH evokes transient increases in [Ca2+]i and elevates basal Ca2+ levels in resting chondrocytes. The transient increases were initiated intracellularly, were abrogated by the phospholipase C-specific inhibitor, U73122, and were partly attenuated by myo-inositol 1,4,5-triphosphate receptor inhibition via 10 mm caffeine. The initial intracellular release also resulted in store-operated calcium entry, presumably through store-operated channels. Dexamethasone priming increased both the initial ACTH-evoked [Ca2+]i release and the subsequent store-operated calcium entry. These data demonstrate roles for ACTH and glucocorticoid in the regulation of chondrocyte terminal differentiation. Because the actions of ACTH are mediated through known G protein-coupled receptors, the melanocortin receptors, these data may provide a new therapeutic target in the treatment of growth deficiencies and cartilage degeneration.
Molecular Modeling Studies on Zeolite Catalysts for Shape-Selective Electrophilic Substitution: I Acylation of 2-Methoxynaphthalene
Authors: Bharathi Patibandla , Waghmode Suresh B , Sivasanker Subramanian , Vetrivel Rajappan
Published: April 2005

The diffusion characteristics of acylated 2-methoxynaphthalene inside large pore zeolites were investigated. The interaction of the three isomers with fully siliceous zeolite lattices was studied by energy-minimization calculations. The favorable adsorption sites and the orientation of the acylated products of 2-methoxynaphthalene were analyzed in detail. Three large pore zeolites having 12 m channels were selected: (i) mordenite with an elliptical 1-d channel, (ii) zeolite-L with a circular channel and 2-d cages, and (iii) zeolite-β with circular 3-d channel systems. It was observed that the shape selectivity properties of the zeolites could be profitably used to produce 2-acyl-6-methoxynaphthalene. In the case of mordenite, the diffusion of all three isomers is facile, whereas in the case of zeolite-L, the diffusion of 1-acyl-7-methoxynaphthalene is more facile than 2-acyl-6-methoxynaphthalene and 1-acyl-2-methoxynaphthalene. In the case of zeolite-β, the energy barrier for the diffusion of 2-acyl-6-methoxynaphthalene is significantly smaller than those of the other two isomers. Thus zeolite-β is predicted to be a suitable catalyst for the shape-selective acylation of 2-methoxynaphthalene to 2-acyl-6-methoxynaphthalene.
Immobilization of Photosynthetic Reaction Center Complexes onto a Hydroquinonethiol-Modified Gold Electrode
Authors: Matsumoto Kiyoharu , Nomura Kazuhiro , Tohnai Yasunari , Fujioka Shuji , Wada Masanori , Erabi Tatsuo
Published: April 2005

The immobilization of reaction center complexes onto a gold electrode was attempted through the binding affinity between reaction centers and hydroquinone-2-thiol adsorbed on an electrode surface. The largest anodic photoresponse by immobilized reaction centers was observed using ubiquinone B-depleted reaction centers and with the pre-oxidation of adsorbed hydroquinone-2-thiol, indicating that the degree of the orientation of reaction center particles increases through the binding affinity between vacant QB-sites in the particles and p-benzoquinonethiol. This anodic photoresponse could be elongated over a period of 5 h (2500 cycles of turnover number) by adding cytochrome c2 into the electrolytic solution.
Fluorescence Polarization of Inclusion Complexes of β-Cyclodextrin with 6-Anilino-2-naphthalenesulfonate and 8-Anilino-1-naphthalenesulfonate in Aqueous d-Glucose Solutions
Authors: Hamai Sanyo
Published: April 2005

In aqueous and aqueous d-glucose solutions, 6-anilino-2-naphthalenesulfonate (2,6-ANS) and 8-anilino-1-naphthalenesulfonate (1,8-ANS) form 1:1 inclusion complexes with β-CD. The molecular volume of 2,6-ANS bound to the β-CD cavity has been evaluated to be 4.7 nm3 from the viscosity dependence (Perrin plot) of the 2,6-ANS fluorescence polarization. This value indicates that 2,6-ANS incorporated into the β-CD cavity rotates as the inclusion complex on a fluorescence lifetime scale. The molecular volume of 2,6-ANS in solution without β-CD has been evaluated to be 0.88 nm3, which provides additional evidence for the whole rotation of the β-CD–2,6-ANS inclusion complex. The molecular volume of 1,8-ANS bound to the β-CD has been evaluated to be 2.7 nm3, which is comparable to the calculated molecular volume (1.9 nm3) of β-CD, indicating that 1,8-ANS most likely rotates as the inclusion complex. The fact that the molecular volume of the 1,8-ANS inclusion complex is smaller than that of the 2,6-ANS inclusion complex may be attributed to the differences in the binding site of β-CD and the substitution positions of anilino and sulfonato groups.
Multielement Determination of Trace Elements in Coastal Seawater by Inductively Coupled Plasma Mass Spectrometry with Aid of Chelating Resin Preconcentration
Authors: Yabutani Tomoki , Ji Shan , Mouri Fumihiko , Sawatari Hideyuki , Itoh Akihide , Chiba Koichi , Haraguchi Hiroki
Published: April 2005

The multielement determination of trace elements in coastal seawater by inductively coupled plasma mass spectrometry has been investigated with the aid of chelating resin preconcentration. First, each coastal seawater sample (250 ml) was treated with a chelating resin (Chelex 100) at pH 6 for preconcentration of trace elements. After filtration with a glass filter, the resin on the filter was carefully rinsed with 8 ml of 1 M ammonium acetate solution. Then, trace elements adsorbed on the resin were eluted with 6 ml of 2 M HNO3. As a result, the preconcentration factor of 41.7 fold was obtained, with the total concentration of matrix elements (Na, K, Mg, and Ca) less than 200 mg dm−3. The recovery values were larger than 80% for 22 elements among 29 elements determined. The present method was applied to the determination of trace elements in the coastal seawater certified reference material CASS-3, issued from National Research Council of Canada (NRC), as well as to the coastal seawater sample collected from Tokoname off-shore.
Dioxomolybdenum(VI) and Dioxotungsten(VI) Structure with Mono(Dithiolato) Coordination: Crystal Structures, Properties and Reactivity of [{MVIO2(dithiolato)}2(μ-O)]2− (M = Mo and W) Complexes
Authors: Oku Hiroyuki , Ueyama Norikazu , Nakamura Akira
Published: April 2005

Novel mono(dithiolato) molybdenum(VI) and tungsten(VI) complexes were isolated through the searching for potential active species in the catalytic air oxidation of benzoin by [MoVO(SR)4]− complexes. Among these, (NEt4)2[{MoVIO2(3-triphenylsilyl-1,2-benzenedithiolato)}2(μ-O)]·2DMF (1), (PPh4)2[{WVIO2(1,2-benzenedithiolato)}2(μ-O)] (3), and (NEt4)2[{WVIO2(2,3-naphthalenedithiolato)}2(μ-O)] (5) were structurally characterized by X-ray crystallography. The electrochemical, electronic, as well as Raman/IR spectral properties of the tungsten complexes, 3 and 5, have been investigated and compared with the corresponding bis(dithiolato) complexes, e.g. [WVIO2(dithiolato)2]2−. The μ-oxo-binuclear species, [{MoVIO2(SR)2}2(μ-O)]2−, is proposed as a possible active species for the catalytic air oxidation of benzoin by the Mo(V) thiolato complexes.
Sulfur-Bridged Incomplete Cubane-Type Iminodiacetato Molybdenum Clusters: Geometrical Isomers and Their Isomerization
Authors: Shibahara Takashi , Yoshida Shun , Maeyama Masataka , Kojima Masaaki
Published: April 2005

Reaction of the incomplete cubane-type aqua clusters [Mo3(μ3-S)(μ-S)3(H2O)9]4+ (A) with H2ida ( = iminodiacetic acid) followed by ion exchange separation gave four geometrical isomers of [Mo3(μ3-S)(μ-S)3(ida)3]2− (hereafter [Mo3S4(ida)3]2−; A1, A2, A3, and A4 based on the elution sequence), which were isolated as solid samples: Ca[Mo3S4(ida)3]·12H2O (A1′), Ca[Mo3S4(ida)3]·21H2O (A2′), Ca[Mo3S4(ida)3]·10H2O (A3′), and Ca[Mo3S4(ida)3]·14H2O (A4′), respectively. The X-ray structural analyses of A2′ and A4′ revealed that the three nitrogen atoms of three ida ligands in each isomer have the configuration of “trans, trans, cis” and “cis, cis, cis” to μ3-S’s, respectively. The X-ray structure of A1′ has already been determined to have “trans, trans, trans” configuration, therefore, that of A3′ is estimated to have “trans, cis, cis” configuration. HPLC analysis reveals that each isomer isomerizes, cis–transconversion of the ida ligand occurring one by one, and that in equilibrium the anions A1 (18%), A2 (68%), and A3 (14%) exist and A4 does not exist. The advent of A4 is possible only in the course of preparation from A and H2ida.
Generation of Nitrile Oxides from Oxime Derivatives by the Oxidation with Ammonium Hexanitratocerate(IV)
Authors: Arai Noriyoshi , Iwakoshi Mitsuhiko , Tanabe Katsuhiko , Narasaka Koichi
Published: April 2005

Aromatic and aliphatic nitrile oxides are generated by the oxidation of α-hydroxyimino carboxylic acid with ammonium hexanitratocerate(IV). They react with olefinic and acetylenic dipolarophiles to give the corresponding cycloaddition products in good yield. The oxidation of α-oxo aldoximes also affords α-oxo carbonitrile oxides.
A Convenient Synthesis of (E)-4-Alkoxy-2-amino-3-butenoic Acid Derivatives
Authors: Kobayashi Kazuhiro , Irisawa Susumu , Akamatsu Hideki , Takahashi Masaki , Kitamura Taichi , Tanmatsu Miyuki , Morikawa Osamu , Konishi Hisatoshi
Published: April 2005

(E)-4-Alkoxy-2-formylamino-3-butenoic acid esters have been prepared in two steps from 3-alkoxy-1-isocyanopropenes. The method is based on the reaction of 3-alkoxy-1-isocyano-1-lithiopropenes, which can be generated by the treatment of 3-alkoxy-1-isocyanopropenes with LDA in THF at −78 °C, with alkyl chlorocarbonates, affording 4-alkoxy-2-isocyano-3-butenoates. These isocyano esters have been easily transformed into the corresponding formylamino esters by treating with concd HCl in Et2O at −20 °C. Subsequently, the introduction of a substituent into the 2-position has been achieved by ethoxycarbonylation with ethyl chlorocarbonate, followed by alkylation with alkyl halides by using hexamethylphosphoric triamide (HMPA) as a co-solvent. The resulting alkylated isocyano 3-butenoates have been similarly hydrolyzed with concd HCl to the corresponding 2-formylamino-3-butenoates.
Palladium-Catalyzed Cross-Coupling of Benzyl Ketones and α,β-Unsaturated Carbonyl and Phenolic Compounds with o-Dibromobenzenes to Produce Cyclic Products
Authors: Terao Yoshito , Satoh Tetsuya , Miura Masahiro , Nomura Masakatsu
Published: April 2005

A number of carbonyl and phenolic compounds efficiently couple with o-dibromobenzenes in the presence of a palladium catalyst and a base to give the corresponding oxygen-containing heterocycles or carbocyclic compounds. Thus, from the reactions of benzyl phenyl ketones, 1-naphthols, and α,β-unsaturated aldehydes and ketones, benzofuran, benzopyran, benzocyclobutane, and indene derivatives, respectively, are produced selectively via the successive formation of C–C and C–O bonds or of two C–C bonds.
Immunohistochemical Localization of P-glycoprotein in Rat Brain and Detection of Its Increased Expression by Seizures Are Sensitive to Fixation and Staining Variables
Authors: Volk Holger , Potschka Heidrun , Löscher Wolfgang
Published: April 2005

The MDR1 gene product, P-glycoprotein (P-gp), was shown to confer multi-drug resistance to cancer cells, but its overexpression is also suggested to be involved in pharmacoresistance of epilepsy by acting as an energy-dependent drug-efflux pump in the blood-brain barrier (BBB). In normal brain tissue, P-gp is almost exclusively expressed by capillary endothelial cells (EC) of the BBB, whereas little or no expression is detected in other cell types. Increased P-gp expression was observed after seizures, but localization of this increase, i.e., within brain capillary EC or within parenchymal or perivascular astrocytes, which contribute to the BBB function, is controversial. To test whether these antithetic data arise from unusual properties of the antigen itself, we compared different immunohistochemical techniques and monoclonal or polyclonal antibodies to P-gp in normal rat brain and rat brain after kainate-induced seizures. Using acetone-fixed cryostat sections of snap-frozen tissue, strong P-gp labeling was detected in EC and, after seizures, in hippocampal neurons, but not in astrocytes. In contrast, EC and neuronal P-gp immunolabeling were not seen in paraformaldehyde-fixed sections, whereas both perivascular and parenchymal astrocytes exhibited strong P-gp labeling after seizures. The lack of P-gp labeling in EC by paraformaldehyde fixation, was reversed by treatment of the sections with acetate/ethanol. These experiments demonstrate that various fixation conditions have a striking effect on the immunohistochemical localization of P-gp in rat brain and detection of its increased expression by seizures. When data obtained from different immunohistochemical techniques are taken together, seizures seem to induce overexpression of P-gp in four different cell types, i.e., EC, perivascular astrocytes, parenchymal astrocytes, and neurons.
Corrosion of commercial spent nuclear fuel. 2. Radiochemical analyses of metastudtite and leachates
Authors: McNamara Bruce , Hanson Brady D. , Buck Edgar C. , Soderquist Chuck
Published: April 2005

Immersing commercial spent nuclear fuel (CSNF) in deionized water produced two corrosion products after a 2-year contact period. Suspensions of aggregates were observed to form at the air–water interface for each of five samples. These suspended aggregates were characterized by X-ray diffraction (XRD) to be metastudtite (UO4·2H2O), while the corrosion present on the surface of the fuel itself was determined to be studtite [(UO2)(O2)(H2O)2](H2O)2]. The presence of unreacted UO2matrix was below the limits of detection by XRD for the three samples examined. The result prompted a radiochemical analysis of the solids collected from the sample air–water interface. The analysis indicated that high concentrations of90Sr,137Cs, and99Tc, relative to the fuel inventory, had concentrated at the air–water interface along with the aggregates of metastudtite. Concentrations of241Am were at least two orders of magnitude lower than expected in these solids, and retention of237Np and239Pu into the corrosion product was observed. The combined radiochemical analyses of the air–water interface aggregates and leachate samples are a rare example of radionuclide partitioning to an alteration phase and may provide preliminary evidence for mechanisms that give rise to such noticeable departures from fuel-inventory values. The leachate radiochemical data are compared to existing data from hydration of the same CSNF.
Hybrid twinning – a cooperative type of oriented crystal association
Authors: Nespolo Massimo , Ferraris Giovanni
Published: April 2005

The reticular theory of twinning is extended to include the contribution of different, coexisting sublattices that consist of quasi-restored nodes (cooperative sublattices) and are characterized by a specific superposition index. The overall degree of quasi-restoration of the twin lattice is a function of the superposition index of the cooperative sublattices, and is expressed by a new parameter, calledeffective twin index, which is the generalization of the classical twin index. Twins where the effective twin index is lower than the classical twin index are termedhybrid twins. Several twins (e.g. twins of pyrite and of forsterite) that could not so far be explained by the reticular theory because of their too high twin index are interpreted as hybrid twins. The effect of hybrid twins on diffraction patterns is discussed.
Crystal engineering of the composition of pharmaceutical phases. 3. Primary amide supramolecular heterosynthons and their role in the design of pharmaceutical co-crystals
Authors: McMahon Jennifer A. , Bis Joanna A. , Vishweshwar Peddy , Shattock Tanise R. , McLaughlin Olga L. , Zaworotko Michael J.
Published: April 2005

A Cambridge Structural Database study of supramolecular synthons involving primary amides reveals that 84% form amide-amide dimers, whereas 14% form catemers in the absence of other competing hydrogen bond donors and/or acceptors. However in the presence of chemically different but complementary functional groups, e.g., carboxylic acids or aromatic nitrogen moieties, primary amides tend to form supramolecular heterosynthons. Supramolecular heterosynthons represent an opportunity for design of multi-component crystals (co-crystals) in which one molecule contains a primary amide and a second molecule (the co-crystal former) contains the functional group that is complementary to the primary amide. The results of the CSD analysis facilitated the selection of components for seven new primary amide co-crystals: A. Isonicotinamide/2-hydroxybenzoic acid (1:1); B. Nicotinäamide/3-hydroxybenzoic acid (1:1); C. Pyrazinamide/2,5-dihydroxybenzoic acid (1:1); D. Carbamazepine (CBZ)/4,4′-bipyridine (2:1); E. CBZ/4-aminobenzoic acid (2:1); F. CBZ/4-aminobenzoic acid/H2O (2:1:1); G. CBZ/2,6-pyridinedicarboxylic acid (1:1). The molecular recognition events involving the amide moieties are discussed in the context of our experimental results and their implications for crystal engineering of pharmaceutical co-crystals.
Neutron single crystal diffraction: techniques and applications in molecular systems
Authors: Wilson Chick C.
Published: April 2005

Single crystal neutron diffraction is a powerful method for the investigation of molecular structure, and in many cases is found to be an excellent complement to X-ray diffraction. The ability of neutron diffraction to determine the position of the atomic nucleus, rather than the electron density, is key to its use in structural studies. Among other advantages, this lends the neutron the ability to determine accurately the positions (and displacement parameters) of light atoms. In the context of molecular systems, neutron diffraction is thus very well suited to the determination of hydrogen atom parameters, which are key to many applications in molecular structure determination, including hydrogen bonded systems, organometallic materials and in macromolecular structures.

This article briefly summarises some of the applications to which single crystal neutron diffraction has been put in the study of molecular structure, together with an account of the techniques and instrumentation used for these experiments. Particular account is taken of recent developments in instrumentation, and the new scientific applications that have resulted from these, along with a forward look to some of the exciting developments currently taking place in this field. These include instruments with dramatically enhanced detector arrays, other optimisations to improve count-rate and performance, the construction of new neutron sources and exciting new instruments being planned for these sources.
Combined Linkage and Association Mapping of Quantitative Trait Loci by Multiple Markers
Authors: Jung Jeesun , Fan Ruzong , Jin Lei
Published: April 2005

Using multiple diallelic markers, variance component models are proposed for high-resolution combined linkage and association mapping of quantitative trait loci (QTL) based on nuclear families. The objective is to build a model that may fully use marker information for fine association mapping of QTL in the presence of prior linkage. The measures of linkage disequilibrium and the genetic effects are incorporated in the mean coefficients and are decomposed into orthogonal additive and dominance effects. The linkage information is modeled in variance-covariance matrices. Hence, the proposed methods model both association and linkage in a unified model. On the basis of marker information, a multipoint interval mapping method is provided to estimate the proportion of allele sharing identical by descent (IBD) and the probability of sharing two alleles IBD at a putative QTL for a sib-pair. To test the association between the trait locus and the markers, both likelihood-ratio tests and F-tests can be constructed on the basis of the proposed models. In addition, analytical formulas of noncentrality parameter approximations of the F-test statistics are provided. Type I error rates of the proposed test statistics are calculated to show their robustness. After comparing with the association between-family and association within-family (AbAw) approach by Abecasis and Fulker et al., it is found that the method proposed in this article is more powerful and advantageous based on simulation study and power calculation. By power and sample size comparison, it is shown that models that use more markers may have higher power than models that use fewer markers. The multiple-marker analysis can be more advantageous and has higher power in fine mapping QTL. As an application, the Genetic Analysis Workshop 12 German asthma data are analyzed using the proposed methods.
A Postsynaptic Role for Rhp55/57 That Is Responsible for Cell Death in Δrqh1 Mutants Following Replication Arrest in Schizosaccharomyces pombe
Authors: Hope Justin C , Maftahi Mohamed , Freyer Greg A
Published: April 2005

Following replication arrest, multiple cellular responses are triggered to maintain genomic integrity. In fission yeast, the RecQ helicase, Rqh1, plays a critical role in this process. This is demonstrated in Δrqh1 cells that, following treatment with hydroxyurea (HU), undergo an aberrant mitosis leading to cell death. Previous data suggest that Rqh1 functions with homologous recombination (HR) in recovery from replication arrest. We have found that loss of the HR genes rhp55+ or rhp57+, but not rhp51+ or rhp54+, suppresses the HU sensitivity of Δrqh1 cells. Much of this suppression requires Rhp51 and Rhp54. In addition, this suppression is partially dependent on swi5+. In budding yeast, overexpressing Rad51 (the Rhp51 homolog) minimized the need for Rad55/57 (Rhp55/57) in nucleoprotein filament formation. We overexpressed Rhp51 in Schizosaccharomyces pombe and found that it greatly reduced the requirement for Rhp55/57 in recovery from DNA damage. However, overexpressing Rhp51 did not change the Δrhp55 suppression of the HU sensitivity of Δrqh1, supporting an Rhp55/57 function during HR independent of nucleoprotein filament formation. These results are consistent with Rqh1 playing a role late in HR following replication arrest and provide evidence for a postsynaptic function for Rhp55/57.
A Genomics Approach to the Detection of Positive Selection in Cattle:
Authors: Lynn David J , Freeman Abigail R , Murray Caitriona , Bradley Daniel G
Published: April 2005

The detection of adaptive evolution at the molecular level is of interest not only as an insight into the process of evolution but also because of its functional implications for genes of interest. Here, we present the first genomics approach to detecting positive selection operating on the Bos taurus lineage, an important domestic species. This analysis led to the identification of the T-cell and natural killer (NK) cell receptor cluster of differentiation 2 (CD2) as having a strong signal of selection. Further detailed investigation of CD2 revealed that this gene was subject to positive selection during the evolution of a number of mammalian lineages. Moreover, we show that selection has operated primarily on the extracellular domain of CD2 and discuss the implications of this for an important regulator of the adaptive immune response.
Subdivision of Large Introns in Drosophila by Recursive Splicing at Nonexonic Elements
Authors: Burnette James M , Miyamoto-Sato Etsuko , Schaub Marc A , Conklin Jamie , Lopez A Javier
Published: April 2005

Many genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated. We present bioinformatic, phylogenetic, and experimental evidence in Drosophila for a mechanism that subdivides many large introns by recursive splicing at nonexonic elements and alternative exons. Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns >20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns <10 kb. The predicted sites in long introns are highly conserved between Drosophila melanogaster and Drosophila pseudoobscura, despite extensive divergence of other sequences within the same introns. These patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns. Experimental analyses of in vivo processing intermediates and lariat products from four large introns in the unrelated genes kuzbanian, outspread, and Ultrabithorax confirmed that these introns are removed by a series of recursive splicing steps using the predicted nonexonic sites. Mutation of nonexonic site RP3 within Ultrabithorax also confirmed that recursive splicing is the predominant processing pathway even with a shortened version of the intron. We discuss currently known and potential roles for recursive splicing.
Interaction of the Saccharomyces cerevisiae Cortical Actin Patch Protein Rvs167p With Proteins Involved in ER to Golgi Vesicle Trafficking
Authors: Friesen Helena , Colwill Karen , Robertson Karen , Schub Oliver , Andrews Brenda
Published: April 2005

We have used affinity chromatography to identify two proteins that bind to the SH3 domain of the actin cytoskeleton protein Rvs167p: Gyp5p and Gyl1p. Gyp5p has been shown to be a GTPase activating protein (GAP) for Ypt1p, a Rab GTPase involved in ER to Golgi trafficking; Gyl1p is a protein that resembles Gyp5p and has recently been shown to colocalize with and belong to the same protein complex as Gyp5p. We show that Gyl1p and Gyp5p interact directly with each other, likely through their carboxy-terminal coiled-coil regions. In assays of GAP activity, Gyp5p had GAP activity toward Ypt1p and we found that this activity was stimulated by the addition of Gyl1p. Gyl1p had no GAP activity toward Ypt1p. Genetic experiments suggest a role for Gyp5p and Gyl1p in ER to Golgi trafficking, consistent with their biochemical role. Since Rvs167p has a previously characterized role in endocytosis and we have shown here that it interacts with proteins involved in Golgi vesicle trafficking, we suggest that Rvs167p may have a general role in vesicle trafficking.
Mutations in Snail Family Genes Enhance Craniosynostosis of Twist1 Haplo-insufficient Mice
Authors: Oram Kathleen F , Gridley Thomas
Published: April 2005

In Drosophila, mutations in the Twist gene interact with mutations in the Snail gene. We show that the mouse Twist1 mutation interacts with Snai1 and Snai2 mutations to enhance aberrant cranial suture fusion, demonstrating that genetic interactions between genes of the Twist and Snail families have been conserved during evolution.
Attributable Cost of Nosocomial Primary Bloodstream Infection in Pediatric Intensive Care Unit Patients
Authors: Elward Alexis M. , Hollenbeak Christopher S. , Warren David K. , Fraser Victoria J.
Published: April 2005

Objective. To determine the attributable cost of nosocomial primary bloodstream infections (BSIs) in PICU patients.

Methods. A prospective cohort study was conducted of the PICU of the St Louis Children's Hospital, a 235-bed academic tertiary care center. All patients who were admitted to the PICU were included unless they met the following exclusion criteria: age >18 years, death within 24 hours of PICU admission, admission to the NICU service. Total and direct medical costs of PICU and hospital stay for patients with and without nosocomial primary BSI were measured.

Results. Fifty-seven children developed 65 episodes of primary BSIs during their PICU stay. The rate of BSI in this population was 13.8 per 1000 central venous catheter days. In multiple linear regression analysis, severity of illness as measured by the admission Pediatric Risk of Mortality Score III, congenital heart disease, underlying lung disease, ventilator days, transplant (solid organ and bone marrow), and nosocomial primary BSI were independent predictors of PICU direct costs. The direct cost of PICU admission for patients with nosocomial primary BSI was $45 615 and for the patients without primary BSI was $6396.

Conclusions. After controlling for age, severity of illness, underlying disease, and ventilator days, we found that the direct cost of PICU admission attributable to nosocomial primary BSI was $39 219. The prevention of these infections through specific interventions is likely to be cost-effective.
Teen Reach: Outcomes From a Randomized, Controlled Trial of a Tobacco Reduction Program for Teens Seen in Primary Medical Care
Authors: Hollis Jack F. , Polen Michael R. , Whitlock Evelyn P. , Lichtenstein Edward , Mullooly John P. , Velicer Wayne F. , Redding Colleen A.
Published: April 2005

Objective. To test the long-term efficacy of brief counseling plus a computer-based tobacco intervention for teens being seen for routine medical care.

Methods. Both smoking and nonsmoking teens, 14 to 17 years of age, who were being seen for routine visits were eligible for this 2-arm controlled trial. Staff members approached teens in waiting rooms of 7 large pediatric and family practice departments within a group-practice health maintenance organization. Of 3747 teens invited at ≥1 visits, 2526 (67%) consented and were randomized to tobacco intervention or brief dietary advice. The tobacco intervention was individually tailored on the basis of smoking status and stage of change. It included a 30-second clinician advice message, a 10-minute interactive computer program, a 5-minute motivational interview, and up to two 10-minute telephone or in-person booster sessions. The control intervention was a 5-minute motivational intervention to promote increased consumption of fruits and vegetables. Follow-up smoking status was assessed after 1 and 2 years.

Results. Abstinence rates after 2 years were significantly higher for the tobacco intervention arm, relative to the control group, in the combined sample of baseline smokers and nonsmokers (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.03–1.47). Treatment effects were particularly strong among baseline self-described smokers (OR: 2.42; 95% CI: 1.40–4.16) but were not significant for baseline nonsmokers (OR: 1.25; 95% CI: 0.97–1.61) or for those who had “experimented” in the past month at baseline (OR: 0.95; 95% CI: 0.45–1.98).

Conclusions. Brief, computer-assisted, tobacco intervention during routine medical care increased the smoking cessation rate among self-described smokers but was less effective in preventing smoking onset.
Have There Been Changes in Children's Psychosomatic Symptoms? A 10-Year Comparison From Finland
Authors: Santalahti Paivi , Aromaa Minna , Sourander Andre , Helenius Hans , Piha Jorma
Published: April 2005

Objectives. The aims of the study were to determine whether the prevalence of children's somatic symptoms, such as headache, abdominal pain, other pain, and nausea and vomiting, changed from 1989 to 1999 and to study the similarity of parents' and children's reports of the child's symptoms. Furthermore, the aims were to explore possible comorbidity in somatic symptoms and to investigate the associations between somatic and psychiatric symptoms.

Methods. Two cross-sectional, representative samples were compared. All children born in 1981 (1989 sample, n = 985) and 1991 (1999 sample, n = 962) and living in selected school districts in southwest Finland served as study samples. The response rate for the 1989 sample was 95% and that for the 1999 sample was 86%. Both children and parents were asked about the children's somatic symptoms, whereas parents, children, and teachers were asked about psychiatric symptoms. To study psychiatric symptoms, the Children's Depression Inventory and Rutter's parent and teacher scales were used.

Results. The prevalence of frequent headaches and abdominal pain increased somewhat from 1989 to 1999. Parents often failed to recognize their children's psychosomatic problems. Child-reported somatic symptoms were associated with conduct and hyperactivity symptoms, in addition to a previously well-documented association with depression. In associations between somatic symptoms and psychiatric symptoms, there were some differences between the 1989 and 1999 samples.

Conclusions. In clinical work, questions about somatic and psychiatric symptoms should also be addressed to children themselves, because parents and teachers do not always recognize children's symptoms. When somatic problems are being evaluated, psychiatric symptoms should be asked about, and vice versa. More research is needed to explore the reasons for the increased prevalence of somatic symptoms and their associations with psychiatric symptoms.
Effects of Race, Insurance Status, and Hospital Volume on Perforated Appendicitis in Children
Authors: Smink Douglas S. , Fishman Steven J. , Kleinman Ken , Finkelstein Jonathan A.
Published: April 2005

Objective. Previous research suggests that perforated appendicitis is more common in Medicaid patients, but the roles of minority race and hospital volume remain largely unstudied. We sought to investigate the association of perforated appendicitis in children with minority race, insurance status, and hospital volume.

Methods. We conducted a retrospective, population-based cohort study of 33184 children who had an International Classification of Diseases, Ninth Revision diagnosis code for acute appendicitis in The Kids' Inpatient Database, a pediatric database from 22 states in 1997. A multivariate logistic regression model was developed to determine patient and hospital characteristics predictive of perforated appendicitis.

Results. Of 33184 children with acute appendicitis, 10777 (32.5%) were perforated. In multivariate analysis, black (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 1.10–1.39) and Hispanic (OR: 1.19; 95% CI: 1.10–1.29) children were more likely to have perforated appendicitis than white children. Perforation was also more likely in Medicaid patients (OR: 1.30; 95% CI 1.22–1.39) compared with privately insured children. Annual hospital volume of cases of appendicitis was not significantly associated with perforation in multivariate analysis.

Conclusions. Perforated appendicitis disproportionately affected both children of minority race and children insured by Medicaid. No effect of hospital volume was observed. To reduce this racial disparity, efforts should focus on the causes of delayed diagnosis and the treatment of appendicitis in children of minority race.