bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose Finding Study for the Use of Subcutaneous Recombinant Interleukin-2 to Augment Natural Killer Cell Numbers in an Outpatient Setting for Stage 4 Neuroblastoma After Megatherapy and Autologous Stem-Cell Reinfusion
Authors: Ladenstein Ruth , Pötschger Ulrike , Siabalis Dimitris , Garaventa Alberto , Bergeron Christophe , Lewis Ian J. , Stein Jerry , Kohler Janice , Shaw Peter J. , Holter Wolfgang , Pistoia Vito , Michon Jean
Published: December 2010

Purpose

To establish a safe dose of subcutaneous (SC) recombinant interleukin 2 (rIL-2) in an outpatient setting for children with stage 4 neuroblastoma after megatherapy (MGT) and autologous stem-cell reinfusion (ASCR) that is able to sustain an increase of natural-killer cells (NKCs) above the level previously reported for immunomodulatory potency.

Patients and Methods

Between August 1997 and November 2000, 33 patients with stage 4 neuroblastoma entered the study from six countries after receiving MGT/ASCR according to national protocols. Dose levels of 3, 6, and 9 × 106 U rIL-2/m2 were given SC in six 5-day cycles every 2 weeks.

Results

Median age at registration was 4.1 years (range, 1.8 to 7.4). Median observation time was 5 years (range, 4 to 9.8). Increase of NKCs was achieved in 89% of courses, with more than 100% increase over baseline and/or more than 1,000 NKCs/μL in 58%. On the basis of outpatient dose-limiting toxicity at dose level 3, dose level 2 was chosen for the confirmation stage. At dose level 2, the median increase in absolute NKCs was 1,180 cells/μL for all 83 cycles, corresponding to a median relative NKC increase over baseline of 711%. Fever was frequent but controllable with adequate supportive care; 6.5% of patients were hospitalized. Localized pain was moderate and acceptable. Event-free and overall survival rates at 5 years were 45% (± 9 standard deviation [SD]) and 48% (± 9 SD), respectively.

Conclusion

The low toxicity profile and ability to sustain an increase in NKCs of IL-2 at 6 × 106 U/m2 SC allows its integration in an outpatient setting.
Prophylaxis of Graft-Versus-Host Disease in Unrelated Donor Transplantation With Pentostatin, Tacrolimus, and Mini-Methotrexate: A Phase I/II Controlled, Adaptively Randomized Study
Authors: Parmar Simrit , Andersson Borje S. , Couriel Daniel , Munsell Mark F. , Fernandez-Vina Marcelo , Jones Roy B. , Shpall Elizabeth J. , Popat Uday , Anderlini Paolo , Giralt Sergio , Alousi Amin , Cano Pedro , Bosque Doyle , Hosing Chitra , Silva Leandro de Padua , Westmoreland Michael , Wathen J. Kyle , Berry Donald , Champlin Richard E. , de Lima Marcos J.
Published: December 2010

Purpose

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy.

Patients and Methods

Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m2 with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT.

Results

Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m2 had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m2 or 1.0 mg/m2 versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m2, 1.0 mg/m2, and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m2 group.

Conclusion

Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.
Induction of CD8+T-Cell Responses Against Novel Glioma–Associated Antigen Peptides and Clinical Activity by Vaccinations With α-Type 1 Polarized Dendritic Cells and Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose in Patients With Recurrent Malignant Glioma
Authors: Okada Hideho , Kalinski Pawel , Ueda Ryo , Hoji Aki , Kohanbash Gary , Donegan Teresa E. , Mintz Arlan H. , Engh Johnathan A. , Bartlett David L. , Brown Charles K. , Zeh Herbert , Holtzman Matthew P. , Reinhart Todd A. , Whiteside Theresa L. , Butterfield Lisa H. , Hamilton Ronald L. , Potter Douglas M. , Pollack Ian F. , Salazar Andres M. , Lieberman Frank S.
Published: December 2010

Purpose

A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells (αDC1) loaded with synthetic peptides for glioma-associated antigen (GAA) epitopes and administration of polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in HLA-A2+patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, and gp100.

Patients and Methods

Twenty-two patients (13 with glioblastoma multiforme [GBM], five with anaplastic astrocytoma [AA], three with anaplastic oligodendroglioma [AO], and one with anaplastic oligoastrocytoma [AOA]) received at least one vaccination, and 19 patients received at least four vaccinations at two αDC1 dose levels (1 × or 3 × 107/dose) at 2-week intervals intranodally. Patients also received twice weekly intramuscular injections of 20 μg/kg poly-ICLC. Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines. T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays.

Results

The regimen was well-tolerated. The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58% of patients. Peripheral blood samples demonstrated significant upregulation of type 1 cytokines and chemokines, including interferon-α and CXCL10. Nine (four GBM, two AA, two AO, and one AOA) achieved progression-free status lasting at least 12 months. One patient with recurrent GBM demonstrated sustained complete response. IL-12 production levels by αDC1 positively correlated with time to progression.

Conclusion

These data support safety, immunogenicity, and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines.
BLOOD UNDER THE BRIDGE: REFLECTIONS ON “THINKING SEX”
Authors: Rubin Gayle
Published: December 2010

This article reflects on the intellectual and political circumstances of the publication of Gayle Rubin's 1984 essay “Thinking Sex: Notes for a Radical Theory of the Politics of Sexuality.” In particular, the article considers the context of the feminist “sex wars” of the late 1970s and early 1980s, offering a detailed account of several of the period's key events, publications, and debates. The article also reflects on the relation between this moment in the history of feminism and the history of GLBT and queer scholarship over the past several decades.
THE TIME HAS COME TO THINK ABOUT GAYLE RUBIN
Authors: Stryker Susan
Published: December 2010

This article is a personal testimonial to Gayle Rubin, delivered as an introduction to her keynote address at the 2009 “Rethinking Sex” conference convened in her honor at the University of Pennsylvania. It makes a few brief remarks on Rubin's contribution to the development of transgender studies.
THINKING SEX ETHNOGRAPHICALLY
Authors: Epstein Steven
Published: December 2010

The influence and staying power of Gayle Rubin's essay “Thinking Sex” reflect her success in taking the insights of empirical studies of sexuality—particularly, historically informed ethnography—and drawing out their intellectual and political implications so as to permit an astonishingly interdisciplinary engagement. Part of what Rubin has given social scientists (as well as ethnographically minded humanists) is a model of how to link discourse and representation to the domain of practice as enacted within the lived worlds of erotic communities that are marked by their own rituals, politics, institutions, and spatial configurations.
An endophilin–dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling
Authors: Sundborger Anna , Soderblom Cynthia , Vorontsova Olga , Evergren Emma , Hinshaw Jenny E. , Shupliakov Oleg
Published: December 2010

Clathrin-mediated vesicle recycling in synapses is maintained by a unique set of endocytic proteins and interactions. We show that endophilin localizes in the vesicle pool at rest and in spirals at the necks of clathrin-coated pits (CCPs) during activity in lamprey synapses. Endophilin and dynamin colocalize at the base of the clathrin coat. Protein spirals composed of these proteins on lipid tubes in vitro have a pitch similar to the one observed at necks of CCPs in living synapses, and lipid tubules are thinner than those formed by dynamin alone. Tubulation efficiency and the amount of dynamin recruited to lipid tubes are dramatically increased in the presence of endophilin. Blocking the interactions of the endophilin SH3 domain in situ reduces dynamin accumulation at the neck and prevents the formation of elongated necks observed in the presence of GTPγS. Therefore, endophilin recruits dynamin to a restricted part of the CCP neck, forming a complex, which promotes budding of new synaptic vesicles.
A hidden incoherent switch regulates RCAN1 in the calcineurin–NFAT signaling network
Authors: Shin Sung-Young , Yang Hee Won , Kim Jeong-Rae , Do Heo Won , Cho Kwang-Hyun
Published: December 2010

Regulator of calcineurin 1 (RCAN1) is a key regulator of the calcineurin–NFAT signaling network in organisms ranging from yeast to human, but its functional role is still under debate because different roles of RCAN1 have been suggested under various experimental conditions. To elucidate the mechanisms underlying the RCAN1 regulatory system, we used a systems approach by combining single-cell experimentation with in silico simulations. In particular, we found that the nuclear export of GSK3β, which switches on the facilitative role of RCAN1 in the calcineurin–NFAT signaling pathway, is promoted by PI3K signaling. Based on this, along with integrated information from previous experiments, we developed a mathematical model in which the functional role of RCAN1 changes in a dose-dependent manner: RCAN1 functions as an inhibitor when its levels are low, but as a facilitator when its levels are high. Furthermore, we identified a hidden incoherent regulation switch that mediates this role change, which entails negative regulation through RCAN1 binding to calcineurin and positive regulation through sequential phosphorylation of RCAN1.
Cultural issues and the menopause
Authors: Pitkin Joan
Published: December 2010

Culture is a rather amorphous concept yet has a huge impact on our attitudes to diet, lifestyle, religion, sexuality and, via its influence on society, attitudes to education and health care. The midlife is a time of emotional and hormonal upheaval for any woman so defining the effects on culture on her response is challenging. Much depends on the value she places on her fertility and sexuality together with her own goals and aspirations, yet these are also influenced by culture. Very few traditional cultures survive in isolation for comparison. Shifting populations mean counter influences and transitional societies can be ambivalent. Emigrants and refugees transplanted into a different environment may struggle with the concept of acculturation. In time, all cultures evolve regardless. Finally, there may be biological and hormonal differences between races. This article seeks to place these different forces into context.
Management of women requesting subtotal hysterectomy
Authors: Maina William C , Morris Edward P
Published: December 2010

Subtotal hysterectomy (SH), which is also referred to as supracervical hysterectomy, is a common gynaecological procedure in which the uterus is removed and the cervix is retained. There is continuing debate about the advantages and disadvantages of SH compared with total abdominal hysterectomy. Persistent vaginal bleeding and the need for continued cervical screening appear to be the main disadvantages of SH. The procedure is often combined with removal of the ovaries. Women should be counselled appropriately prior to removal of their ovaries. Following an internal audit of practice of hormone replacement therapy (HRT) prescription within our own unit, we discovered that there were inconsistencies in the prescription of HRT following SH which led us to investigate this matter further. We concluded that evidence is lacking to guide HRT prescription following SH and bilateral oophorectomy and propose content that can help produce guidelines for the counselling of women prior to SH and prescription of HRT.
Menopause and sexual desire: the role of testosterone
Authors: Nappi Rossella E , Albani Francesca , Santamaria Valentina , Tonani Silvia , Martini Ellis , Terreno Erica , Brambilla Emanuela , Polatti Franco
Published: December 2010

The present short review underlines the role of testosterone (T) in the motivational and satisfaction components of women's sexuality and critically discusses the strategies to treat hypoactive sexual desire disorder (HSDD), a condition of low desire associated with personal and/or interpersonal difficulties, which is more common in surgical menopausal women. There are multiple ways androgens target the brain regions (hypothalamic, limbic and cortical) involved in sexual function and behaviour. Even though circulating available androgens have been implicated in several domains of sexual response, they seem to be related weakly to symptoms, such as low sexual desire, poor sexual arousal, orgasm and diminished well-being in postmenopausal women. The possibilities of treating low sexual desire/HSDD are multifaceted and should include the combination of pharmacological treatments able to maximize biological signals driving the sexual response, and individualized psychosocial therapies in order to overcome personal and relational difficulties. Transdermal T has been shown to be effective at a dose of 300 µg/day both in surgically and naturally menopausal women replaced with estrogen or not, without any relevant side-effects. However, the decision to treat postmenopausal women with HSDD with T is mainly based on clinical judgement, after informed consent regarding the unknown long-term risks.
Rickettsial infection with hemophagocytosis
Authors: Jayakrishnan M P , Veny John , Feroze M
Published: December 2010

A five-year-old girl admitted with scrub typhus developed multiple organ dysfunction associated with hyperferritinaemia, hypofibrinogenaemia and hyperlipidaemia. Bone marrow aspiration studies confirmed haemophagocytic lymphohistiocytosis (HLH). HLH is a syndrome characterized by the uncontrolled activation and proliferation of macrophages and T-cells and can occur together with infections, connective tissue disorders, malignancies and genetic disorders.
Urinary stone composition in pediatric patients: a retrospective study of 205 cases
Authors: Alaya Akram , Nouri Abdellatif , Najjar Mohamed Fadhel
Published: December 2010

Background:Stone composition has changed substantially over the past decades in developed countries. We studied urinary stone composition in Tunisian children.

Methods:We studied 205 children ranging from 3 months to 16 years old age and who were diagnosed as having urinary stones (122 boys and 83 girls). Stone analysis was performed respectively using a stereomicroscope and by infrared spectroscopy to determine, respectively, the morphological type and molecular composition of each.

Results:Of 205 stones analysed, 77 (37.5%) were composed of a single constituent. Calcium oxalate (CaOx) stone were predominant, being a constituent of 54.7% of stones, followed by calcium phosphate and purines; 14.6% of cases. Calcium oxalate monohydrate was more frequently seen in girls (p<0.01), while struvite was more common in boys (p<0.001). Teenagers were more affected by whewellite stones compared with infants (p<0.05). Purine stones were predominant in 20% of cases, but its prevalence decreased with age.

Conclusions:The increase in calcium oxalate stones in school age children and the decrease of struvite and purines stones confirm the change in the etiology of urolithiasis with respect to age.
Full-scan mass spectral evidence for 3-epi-25-hydroxyvitamin D3 in serum of infants and adults
Authors: Stepman Hedwig C.M. , Vanderroost An , Stöckl Dietmar , Thienpont Linda M.
Published: December 2010

Background: Since the introduction of liquid chromatography-mass spectrometry (LC/MS) for assessing vitamin D status, it has been shown that the C-3 epimer can account for a significant proportion of circulating 25-hydroxyvitamin D3 (25OHD3) concentrations in infants. However, some question whether monitoring a single MS transition at a chromatographic retention time typical for 3-epi-25OHD3 sufficiently warrants conclusions about the identity of the substance generating the signal. Therefore, we aimed to substantiate the evidence for 3-epi-25OHD3 in infants by collision induced dissociation (CID)-MS/MS product ion scans. A second objective was mass spectrometric investigation of the presence and prevalence of the 3-epi metabolite in serum from adults.

Methods: Serum samples from six infants and 32 adults were studied using an ultra performance LC/tandem MS (UPLC/MS/MS) method designed to separate the 3-epi-25OHD3 from 25OHD3. Samples were submitted to liquid/liquid extraction and Sephadex LH-20 fractionation, prior to column-switching UPLC with MS/MS recording of CID product ion spectra of the [M+H]+ precursor ion. The respective standards were analyzed under identical UPLC/MS/MS conditions for comparison.

Results: In the chromatograms of all samples, two peaks eluted with retention characteristics and spectra closely matching those observed for the 25OHD3 and the 3-epi standards. The percentage of the 3-epi metabolite relative to 25OHD3 in infants ranged from 15% to 41%, and in adults from 2.5% to 17%.

Conclusions: This preliminary finding suggests that the prevalence of 3-epi-25OHD3 in serum of infants is considerable, and that even in adults the concentrations of this form should not be neglected.
Rapid microwave digestion and microplate reading format method for urinary iodine determination
Authors: Hedayati Mehdi , Khazan Marjan , Yaghmaee Parichehr , Yeghaneh Marjan Zarif , Behdadfar Leila , Daneshpour Maryam Sadat
Published: December 2010

Background: High temperature and long heating time can be considered the main drawbacks of the conventional digestion methods of urinary iodine determination. The aim of this study was to assess the usefulness of a microwave for digestion and decomposition of urine interfering substances. It may help for shortening the time and increasing the safety of the method.

Methods: In this study, two digestion methods were tested on urine samples. Random urine samples were processed by conventional electrical heat as well as new microwave digestion methods. The urine samples were digested using the two methods mentioned, and then urinary iodine was determined using a colorimetric reaction according to the Sandell-Kolthoff reaction. In order to increase speed and precision of the test, a microplate ELISA reader was used. Sensitivity, precision, and comparison of the results were assessed in both of the methods.

Results: In the case of microwave digestion, only a 10-min period was needed for complete digestion of urine samples. The precision and recovery of the new digestion step was acceptable. Furthermore, comparison of final results of iodine content obtained using the microwave and conventional method showed good correlation.

Conclusions: These results show that a microwave method for urine digestion is advantageous due to its safety and ease of use, and quick preparation of urine samples to eliminate interfering substances and release iodine. Thus, it can replace the conventional electrical heat digestion method.
Mass spectrometry measurement of plasma hepcidin for the prediction of iron overload
Authors: Floreani Annarosa , Navaglia Filippo , Rizzotto Erik Rosa , Basso Daniela , Chiaramonte Maria , Padoan Andrea , Petridis Ioannis , Cazzagon Nora , Testa Roberto , Marra Maurizio , Plebani Mario
Published: December 2010

Background: Hepcidin has emerged as the primary regulator of iron homeostasis. Previous studies on assessing urinary hepcidin are limited. We developed a method for quantifying hepcidin-25 (Hep-25) in plasma using surface-enhanced laser-desorption-ionization time-of-flight mass spectrometry (SELDI-TOF/MS) and a 25-AA peptide as reference standard. The aims of the study were 1) to assess the performance of this method in different conditions of iron metabolism disorders; 2) to assess the diagnostic validity of non-invasive serum biomarkers in the identification of iron overload.

Methods: Validation of the method was performed in 10 patients with type I hemochromatosis (HE) and in 177 subjects previously enrolled in a general population epidemiological study. Among the latter group, 17 had non-alcoholic fatty liver disease, 10 had chronic hepatitis C, and 150 subjects had normal ultrasound, normal liver function tests (LFTs), an alcohol intake <20 g ethanol/day and were negative for the C282Y mutation. The following biomarkers were assayed in each case: plasma Hep-25, C282Y and H63D mutations of the HFE gene; serum iron, ferritin (SF), transferrin saturation, transaminases, γ-glutamyltransferase (GGT), glucose, insulin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides.

Results: Plasma Hep-25 concentrations were higher in HCV+ patients (26.3±7.2 nmol/L) than in controls, and correlated positively with SF (p<0.001). H63D heterozygous subjects revealed a pattern of iron overload that was significantly higher than H63D wild type subjects. Analyzing the data with the Biomarker Pattern 5.0.2. software to identify the most significant biomarkers for discriminating between HE cases and controls allowed us to produce an algorithm with four terminal nodes, which included glucose >4.8 mmol/L and Hep-25/SF ratio ≤6.6 as the main splitters. These variables enabled the correct diagnosis of HE with 100% sensitivity, 93% specificity and an area under the receiver operating characteristic (ROC) curve of 0.993.

Conclusions: Our plasma Hep-25 mass spectrometry method yields measurements that reflect pathological and genetic influences; simple non-invasive biomarkers (Hep-25/SF ratio and glucose) can predict the presence of HE.
APOA5 −1131T/C polymorphism is associated with coronary artery disease in a Chinese population: a meta-analysis
Authors: Guanghua Zhai , Meifen Li , Chaowang Zhu
Published: December 2010

Background: Functional studies suggest that the APOA5 −1131T/C polymorphism plays an important role in triglyceride (TG) metabolism, which is an event contributing to the pathogenesis of coronary artery disease (CAD). However, genetic evidence of its effect on CAD is inconsistent. To assess this correlation, we performed a meta-analysis of published data.

Methods: A comprehensive meta-analysis was performed on nine published studies, with a total sample of 2049 subjects and 2373 controls using a fixed effect model.

Results: Under the fixed effect model, the risk of the disease was significantly higher in subjects with CC genotype in comparison with both TT (OR: 1.99; 95% CI: 1.64–2.41) and TC (OR: 1.48; 95% CI: 1.22–1.80) subjects. Compared with TT homozygotes, there was 43% increase in the incidence of CAD (OR: 1.43; 95% CI: 1.26–1.61) of C carriers (CC+TC). There was no heterogeneity for these effect estimates.

Conclusions: Our findings support the view that −1131T/C polymorphism of the APOA5 gene is associated with CAD and the C allele might be a genetic risk factor that increases susceptibility to CAD.
Crystalluria: prevalence, different types of crystals and the role of infrared spectroscopy
Authors: Verdesca Simona , Fogazzi Giovanni B. , Garigali Giuseppe , Messa Piergiorgio , Daudon Michel
Published: December 2010

Background: Studies on the frequency of the different types of urinary crystals and the role of Fourier transform infrared microspectroscopy (FTIRM) for identification are few. We describe the results of a retrospective study on the prevalence and typology of crystalluria and on the role of FTIRM.

Methods: Urinary crystals were identified using the combined knowledge of crystal morphology, birefringence features and urine pH (combined approach). When this was inconclusive, FTIRM was performed.

Results: Crystalluria was found in 807 out of 9834 samples (8.2%). In 793, the combined approach identified “typical” crystals, while in 14 FTIRM was needed to identify “atypical” crystals. Among “typical crystals”, calcium oxalate (75.9%), uric acid (25.9%) and amorphous urates (7.9%), alone or in combination, were the most frequent. Brushite, ammonium biurate and cystine were the most rare (0.1%–0.7%). FTIRM identified 12 of 14 atypical crystals: three crystals were due to a drug (amoxicillin, indinavir, doubtful phenytoloxamine); four were due to calcium oxalate mono- or bihydrate, uric acid bihydrate or struvite; five were due to calcium carbonate, Tamm-Horsfall glycoprotein, or rare salt combinations.

Conclusions: Crystalluria is not rare and most crystals can be identified by the combined approach. Occasionally, identification of crystals will require FTIRM.
Effect of metal ions on some pharmacologically relevant interactions involving fluoroquinolone antibiotics
Authors: Seedher Neelam , Agarwal Pooja
Published: December 2010

Background:Complexation of five metal cations, Fe3+, Al3+, Zn2+, Cu2+and Mg2+with four fluoroquinolones, levofloxacin, sparfloxacin, ciprofloxacin hydrochloride and enrofloxacin and human serum albumin (HSA) has been studied for better understanding of bioavailability of drugs interacting with metals and proteins.

Methods:The binding parameters have been determined using fluorescence and ultraviolet absorption spectroscopic techniques. The effect of metal cations on the interaction of fluoroquinolones with HSA has also been investigated.

Results:The association constants were of the order of 102–104for the fluoroquinolone-metal ion interaction. For a given drug, the chelation potential of Al3+was highest, whereas that of Mg2+was lowest. At a metal ion/drug ratio of 1:1, approximately 50%–73% of metal ion was bound per mole drug in most cases. In the case of HSA-metal ion interaction, for Fe3+and Zn2+ions, there was only one class of binding site, whereas for Al3+and Cu2+ions, two types of binding sites were found. The relative affinity of various metal ions was found to vary as Al3+>Cu2+>Zn2+>Fe3+. The extent of binding was found to be independent of the charge on the ion. Owing to very weak quenching of fluorescence, the association constant for the interaction of Mg2+ion could not be determined by this technique. The binding affinity of all the fluoroquinolones to HSA was found to increase in the presence of Cu2+ions, whereas all other metal ions decreased the binding ­affinity with the exception of levofloxacin in the presence of Zn2+and Al3+ions. Increase in the binding affinity indicated that the metal ions facilitate HSA-fluoroquinolone interaction and fluoroquinolones probably interact with HSA via a metal ion bridge. Decrease in the binding affinity, by contrast, can either be due to the fact that fluoroquinolone-metal ion complex inhibits fluoroquinolone-HSA interaction or metal ions produce conformational changes in the HSA molecule.

Conclusions:Results indicate that metal chelate formation can cause significant reduction in the antimicrobial activity of fluoroquinolone antibiotics. Alteration in the HSA-fluoroquinolone binding affinity in the presence of metal ions could have significant pharmacological effects. Quantitative estimate of the magnitude of interaction of different metal ions could also be obtained from the data.
ZR Vertretung ohne Vertretungsmacht
Authors: Petersen Jens
Published: December 2010

Nachdem in früheren Aufsätzen Botenschaft und Stellvertretung, das Offenkundigkeitsprinzip sowie Bestand und Umfang der Vertretungsmacht dargestellt wurden, behandelt der vorliegende Beitrag den für die Fallbearbeitung besonders wichtigen Bereich der Vertretung ohne Vertretungsmacht.
No Sustained Sound Illusion in Rhythmic Sequences
Authors: Repp Bruno H. , Marcus Rachel J.
Published: December 2010

Recent Research has shown that subdivision of intervals between beats makes the beat tempo seem slower—a "divided time illusion" (DTI) in music. Another temporal illusion described in the psychophysical literature is that a sustained sound seems longer than a silent interval of the same duration. This "sustained sound illusion" (SSI) may be due to acceleration of an internal pacemaker by continuous sound, or it may result from slower perception of sound offsets than of sound onsets. Experiment 1 tested the pacemaker acceleration hypothesis in a rhythmic context by asking musicians to compare or reproduce the tempi of isochronous tone sequences played legato ("filled") or staccato ("unfilled"). There was no indication that legato sequences were perceived as slower than staccato sequences. Experiment 2 tested the delayed offset perception hypothesis by asking musicians to judge the relative time of occurrence of abrupt or decaying tone offsets in the interonset intervals of isochronous sequences. There was no evidence of delayed perception of abrupt offsets, and decaying offsets were perceived only slightly late. These results suggest that the SSI, unlike the DTI, does not occur in rhythmic contexts and thus is probably not of musical relevance. More generally, the results challenge some proposed explanations of this illusion and call for further research on the conditions under which it does occur.
Acoustical Correlates of Timbre and Expressiveness in Clarinet Performance
Authors: Barthet Mathieu , Depalle Philippe , Kronland-Martinet Richard , Ystad Sølvi
Published: December 2010

This study deals with the acoustical factors liable to account for expressiveness in clarinet performances. Mechanical and expressive performances of excerpts from Bach's Suite No. II and Mozart's Quintet for Clarinet and Strings were recorded. Timbre, timing, dynamics, and pitch descriptors were extracted from the recorded performances. The data were processed using a two-way analysis of variance, where the musician's expressive intentions and the note factors were defined as the independent variables. In both musical excerpts, a strong effect of the expressive intention was observed on the timbre (attack time, spectral centroid, odd/even ratio), timing (intertone onset intervals) and dynamics (root mean square envelope) descriptors. The changes in the timbre descriptors were found to depend on the position of the notes in the musical phrases. These results suggest that timbre, as well as timing and dynamics variations, may mediate expressiveness in the musical messages transmitted from performers to listeners.
The Contingent Effect of Social Networks on Organizational Commitment: A Comparison of Instrumental and Expressive Ties in a Multinational High-Technology Company
Authors: Kim Young-Choon , Rhee Mooweon
Published: December 2010

This article examines the relationship between social networks and organizational commitment in a globalized workplace. The authors find not only that organizational commitment is affected by the network properties of size, power connection, and national/ethnic composition but also that these network effects are contingent upon whether the content conveyed in the relationship is instrumental or expressive. Results demonstrate that organizational commitment is (1) positively associated with network size in instrumental ties but not in expressive ties, (2) positively associated with the power of network partners in instrumental ties but less so in expressive ties, and (3) positively associated with national/ethnic diversity in expressive ties but not in instrumental ties. Findings highlight the relational foundation of organizational commitment and suggest that social networks of employees, contingent upon specific content, present different opportunities to their level of commitment to the organization.
Weighing the Consequences of a Deviant Career: Factors Leading to an Exit from Prostitution
Authors: Oselin Sharon S.
Published: December 2010

Research on how individuals leave sex work examines this transition by focusing on either structural/economic conditions that keep them in the trade or internal changes that prompt exiting. Leaving certain roles, such as those deemed criminal and deviant, may be more challenging due to labeling, stigma, and a lack of resources. In this study, the author analyzes the particular factors that lead women to exit street prostitution via enrollment in “helping” organizations. The author finds extant theories do not fully capture how multiple factors combine to pull women off the streets. Rather, the author contends it is both internal and external factors that lead women to initially exit prostitution. This study draws on interviews with thirty-six street prostitutes from four different U.S. cities to address these concerns.
Differences in Earnings among Black and White African Immigrants in the United States, 1980–2000: A Cross-Sectional and Temporal Analysis
Authors: Borch Casey , Corra Mamadi K.
Published: December 2010

This study examines the earnings of African immigrants across three waves of U.S. Census data (1980, 1990, and 2000). The authors find that the U.S. labor market favors White male immigrants, followed by Black male and White female immigrants, and finally Black women. The authors also find that male immigrants earned more per hour than female immigrants regardless of race. Considering change over time, this study finds that the earnings gap between Black and White male immigrants is growing larger over time, the positive association between foreign work experience and earnings is attenuated over time, and for women, the positive effect of earning a college degree on earnings is growing stronger over time. These findings confirm many of the conclusions reached by other race and gender scholars; however, the authors extend this work by focusing on male and female African immigrants, who are largely under-represented in the literature, and by examining change over time.
Socioeconomic Differentials in Global Exposure: A Research Note on Taiwan
Authors: Tsai Ming-Chang , Appelbaum Richard P.
Published: December 2010

Compiling several national survey data collected in Taiwan during 2000–2008, this study examines the differences in individuals' exposure to globalization. The authors conceptualize global exposure in terms of cross-border, transnational network relationships and consumption of global cultural products. The authors explore the effects of socioeconomic differences (education, occupational status, and income) on four dimensions of individual global exposure. The results obtained from the regression analysis suggest that social class is a critical determinant in explaining individual global exposure.
Increased mammographic breast density in acromegaly: quantitative and qualitative assessment
Authors: Tagliafico Alberto , Calabrese Massimo , Tagliafico Giulio , Resmini Eugenia , Martinoli Carlo , Rebora Alberto , Colao Annamaria , Pivonello Rosario , Ferone Diego
Published: December 2010

Context

Mammographic density is a strong independent risk factor for breast cancer, whose prevalence in acromegaly is still controversial.

Objective

To compare breast density in premenopausal acromegalic patients and controls and to determine whether density correlated with disease duration, GH, and IGF1 levels.

Design, setting and participants

A prospective study involving 30 patients and 60 controls matched for age and body mass index.

Interventions

A quantitative computer-aided mammographic density estimation (MDEST) and a qualitative blind evaluation by two experienced radiologists using the breast imaging reporting and data system (BI-RADS) was performed. Totally, 60 (acromegaly) and 120 (controls) craniocaudal and mediolateral oblique mammograms were evaluated in both patients and controls.

Main outcome measures

Breast density.

Results

Patients showed a significantly (P<0.01) increased mammographic breast density with both methods (MDEST: 0.33±0.21% and BI-RADS category: 2.81±0.78) in comparison with controls (MDEST: 0.26±0.19% and BI-RADS category: 2.35±0.61). The agreement between the two methods and inter-observer agreement between the two radiologists were excellent (k=0.63 and k=0.85). In patients grouped according to disease activity (17 controlled and 13 uncontrolled) and medical therapy (15 treated and 15 untreated), no differences were found. All these groups had significantly increased mammographic breast density compared with controls (P<0.01).

A positive correlation was found between mammographic breast density, IGF1 values and disease duration (r=0.29 and r=0.39), whereas it was not found with GH (r=−0.02).

Conclusions

Mammographic breast density in premenopausal acromegalic patients is significantly higher than controls and positively correlated with IGF1 and disease duration.
Evolution of the Genomic Recombination Rate in Murid Rodents
Authors: Dumont Beth L , Payseur Bret A
Published: December 2010

Although very closely related species can differ in their fine-scale patterns of recombination hotspots, variation in the average genomic recombination rate among recently diverged taxa has rarely been surveyed. We measured recombination rates in eight species that collectively represent several temporal scales of divergence within a single rodent family, Muridae. We used a cytological approach that enables in situ visualization of crossovers at meiosis to quantify recombination rates in multiple males from each rodent group. We uncovered large differences in genomic recombination rate between rodent species, which were independent of karyotypic variation. The divergence in genomic recombination rate that we document is not proportional to DNA sequence divergence, suggesting that recombination has evolved at variable rates along the murid phylogeny. Additionally, we document significant variation in genomic recombination rate both within and between subspecies of house mice. Recombination rates estimated in F1 hybrids reveal evidence for sex-linked loci contributing to the evolution of recombination in house mice. Our results provide one of the first detailed portraits of genomic-scale recombination rate variation within a single mammalian family and demonstrate that the low recombination rates in laboratory mice and rats reflect a more general reduction in recombination rate across murid rodents.
Use of Skeletal Surveys to Evaluate for Physical Abuse: Analysis of 703 Consecutive Skeletal Surveys
Authors: Duffy Shanna O. , Squires Janet , Fromkin Janet B. , Berger Rachel P.
Published: December 2010

OBJECTIVES:

The goals were to assess the use of the skeletal survey (SS) to evaluate for physical abuse in a large consecutive sample, to identify characteristics of children most likely to have unsuspected fractures, and to determine how often SS results influenced directly the decision to make a diagnosis of abuse.

METHODS:

A retrospective, descriptive study of a consecutive sample of children who underwent an SS at a single children's hospital over 4 years was performed. Data on demographic characteristics, clinical presentation, SS results, and effects of SS results on clinical diagnoses were collected. A positive SS result was defined as a SS which identified a previously unsuspected fracture(s).

RESULTS:

Of the 703 SSs, 10.8% yielded positive results. Children <6 months of age, children with an apparent life-threatening event or seizure, and children with suspected abusive head trauma had the highest rates of positive SS results. Of children with positive SS results, 79% had ≥1 healing fracture.

CONCLUSIONS:

This is the largest study to date to describe the use of the SS. Almost 11% of SS results were positive. The SS results influenced directly the decision to make a diagnosis of abuse for 50% of children with positive SS results. These data, combined with the high morbidity rates for missed abuse and the large proportion of children with healing fractures detected through SS, suggest that broader use of SS, particularly for high-risk populations, may be warranted.
Adherence to the HPV Vaccine Dosing Intervals and Factors Associated With Completion of 3 Doses
Authors: Widdice Lea E. , Bernstein David I. , Leonard Anthony C. , Marsolo Keith A. , Kahn Jessica A.
Published: December 2010

OBJECTIVE:

The objectives of this study were to determine (1) adherence to the immunization schedule for the human papillomavirus quadrivalent vaccine and (2) factors associated with completion of the 3-dose series.

METHODS:

This was a retrospective review of health information records from an academic medical center. The sample included all 9- to 26-year-old female patients who initiated vaccination within 2 years after quadrivalent vaccine availability. Multivariable logistic regression models were estimated to determine associations with completion of the 3-dose series within 7 and 12 months.

RESULTS:

Among the 3297 female patients who initiated vaccination with human papillomavirus quadrivalent vaccine, 67% self-identified as black and 29% self-identified as white. Fewer than 3% of vaccine doses were received earlier than recommended, but >50% of doses were received late. Completion rates were 14% by 7 months and 28% by 12 months. Independent predictors of completion by 7 months included white versus black race (odds ratio [OR]: 2.04 [95% confidence interval (CI): 1.64–2.56]; P < .001), use of contraception that required intramuscular injections every 3 months (OR: 1.53 [95% CI: 1.12–1.95]; P < .001), and private versus public insurance (OR: 1.31 [95% CI: 1.06–1.63]; P < .05). Age and clinic type were not independent predictors of completion.

CONCLUSIONS:

Adherence to recommended intervals and completion of the vaccine series were low. Lower rates of completion in black patients compared with white patients raises concern that disparities in vaccine completion could exacerbate existing disparities in cervical cancer.
Smoke-Free Air Laws and Asthma Prevalence, Symptoms, and Severity Among Nonsmoking Youth
Authors: Dove Melanie S. , Dockery Douglas W. , Connolly Gregory N.
Published: December 2010

OBJECTIVE:

We investigated the association between smoke-free laws and asthma prevalence, symptoms, and severity among nonsmoking youth (aged 3–15 years).

METHODS:

We examined data from the 1999–2006 National Health and Nutrition Examination Survey, a cross-sectional survey designed to monitor the health and nutritional status of the US population. Survey locations were dichotomized as having or not having at least 1 smoke-free workplace, restaurant, or bar law at the county or state level that covered the entire county population. Asthma prevalence was assessed as self-reported current asthma and as ever having asthma with current symptoms. Asthmatic symptoms included persistent wheeze, chronic night cough, and wheeze-medication use. We also examined asthma severity (asthma attack or emergency-department visit for asthma) and persistent ear infection.

RESULTS:

Smoke-free laws were not associated with current asthma but were significantly associated with lower odds of asthmatic symptoms (odds ratio [OR]: 0.67 [95% confidence interval (CI): 0.48–0.93]) among nonsmoking youth. The association between smoke-free laws and ever having asthma with current symptoms approached significance (OR: 0.74 [95% CI: 0.53–1.03]). Smoke-free laws were associated with lower odds of asthma attacks (OR: 0.66 [95% CI: 0.28–1.56]) and emergency-department visits for asthma (OR: 0.55 [95% CI: 0.27–1.13]), although these results were not statistically significant.

CONCLUSIONS:

Our results suggest that smoke-free laws reduce asthmatic symptoms, including persistent wheeze, chronic night cough, and wheeze-medication use in nonsmoking youth.
Tobacco-Smoke Exposure in Children Who Live in Multiunit Housing
Authors: Wilson Karen M. , Klein Jonathan D. , Blumkin Aaron K. , Gottlieb Mark , Winickoff Jonathan P.
Published: December 2010

OBJECTIVE:

There is no safe level of secondhand tobacco-smoke exposure, and no previous studies have explored multiunit housing as a potential contributor to secondhand tobacco-smoke exposure in children. We hypothesized that children who live in apartments have higher cotinine levels than those who live in detached homes, when controlling for demographics.

METHODS:

We analyzed data from the 2001–2006 National Health and Nutrition Examination Survey. The housing types we included in our study were detached houses (including mobile homes), attached houses, and apartments. Our study subjects were children between the ages of 6 and 18 years. Cotinine levels were used to assess secondhand tobacco-smoke exposure, and those living with someone who smoked inside the home were excluded. χ2 tests, t tests, and Tobit regression models were used in Stata. Sample weights accounted for the complex survey design.

RESULTS:

Of 5002 children in our study, 73% were exposed to secondhand tobacco smoke. Children living in apartments had an increase in cotinine of 45% over those living in detached houses. This increase was 212% (P < .01) for white residents and 46% (P < .03) for black residents, but there was no significant increase for those of other races/ethnicities. At every cutoff level of cotinine, children in apartments had higher rates of exposure. The exposure effect of housing type was most pronounced at lower levels of cotinine.

CONCLUSIONS:

Most children without known secondhand tobacco-smoke exposure inside the home still showed evidence of tobacco-smoke exposure. Children in apartments had higher mean cotinine levels than children in detached houses. Potential causes for this result could be seepage through walls or shared ventilation systems. Smoking bans in multiunit housing may reduce children's exposure to tobacco smoke.