bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Differences in Quality of Life in Stroke Survivors
Authors: Gray Laura J. , Sprigg Nikola , Bath Philip M.W. , Boysen Gudrun , De Deyn Peter Paul , Leys Didier , O’Neill Desmond , Ringelstein E. Bernd
Published: September 2007

Background and Purpose—

Female sex is predictive of poor functional outcome in stroke, even after correction for prognostic factors. Poor quality of life (QoL) is observed in stroke survivors with lower scores seen in the most disabled patients. We used data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST) to assess the relationship between sex and QoL after ischemic stroke.

Methods—

TAIST was a randomized, controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischemic stroke. QoL was measured at 180 days postrandomization using the Short Form-36 health survey, which assesses QoL across 8 domains. The relationship between sex and each domain was assessed using ordinal regression, both unadjusted and adjusted for key prognostic factors.

Results—

Of the 1484 patients randomized into TAIST, 216 had died at 180 days postrandomization. A total of 1268 survivors were included in this analysis, 694 males (55%) and 574 females (45%). Females tended to score lower than males across all QoL domains (apart from general health); statistically significant lower scores were seen for physical functioning (OR: 0.58, 95% CI: 0.47 to 0.72), vitality (OR: 0.79, 95% CI: 0.64 to 0.98), and mental health (OR: 0.75, 95% CI: 0.61 to 0.93). The results for physical functioning and mental health remained significant after adjustment for prognostic variables (OR: 0.73, 95% CI: 0.58 to 0.92; OR: 0.76, 95% CI: 0.60 to 0.95, respectively).

Conclusions—

QoL, in particular physical function and mental health domains, is lower in female patients after stroke. This difference persists even after correction for known prognostic factors such as age and stroke severity.
Long-Term Neuroblast Migration Along Blood Vessels in an Area With Transient Angiogenesis and Increased Vascularization After Stroke
Authors: Thored Pär , Wood James , Arvidsson Andreas , Cammenga Jörg , Kokaia Zaal , Lindvall Olle
Published: September 2007

Background and Purpose—

Stroke induced by middle cerebral artery occlusion (MCAO) causes long-term formation of new striatal neurons from stem/progenitor cells in the subventricular zone (SVZ). We explored whether MCAO leads to hypoxia, changes in vessel density, and angiogenesis in the ipsilateral SVZ and adjacent striatum, and determined the relation between the migrating neuroblasts and the vasculature.

Methods—

Adult rats were subjected to 2 hours of MCAO. Hypoxia was studied by injecting Hypoxyprobe-1 during MCAO or 6 weeks later. Vessel density and length was estimated using stereology. New cells were labeled with 5′-bromo-2′deoxyuridine (BrdU) during weeks 1 and 2 or 7 and 8 after MCAO, and angiogenesis was assessed immunohistochemically with antibodies against BrdU and endothelial cell markers. Distance from neuroblasts to nearest vessel was measured using confocal microscopy.

Results—

The ischemic insult caused transient hypoxia and early, low-grade angiogenesis, but no damage or increase of vascular density in the SVZ. Angiogenesis was detected during the first 2 weeks in the dorsomedial striatum adjacent to the SVZ, which also showed long-lasting increase of vascularization. At 2, 6, and 16 weeks after MCAO, the majority of neuroblasts migrated through this area toward the damage, closely associated with blood vessels.

Conclusions—

The vasculature plays an important role for long-term striatal neurogenesis after stroke. During several months, neuroblasts migrate close to blood vessels through an area exhibiting early vascular remodeling and persistently increased vessel density. Optimizing vascularization should be an important strategy to promote neurogenesis and repair after stroke.
Error Estimation of Buoy, Satellite, and Model Wave Height Data
Authors: Janssen Peter A. E. M. , Abdalla Saleh , Hersbach Hans , Bidlot Jean-Raymond
Published: September 2007

Triple collocation is a powerful method to estimate the rms error in each of three collocated datasets, provided the errors are not correlated. Wave height analyses from the operational European Centre for Medium-Range Weather Forecasts (ECMWF) wave forecasting system over a 4-yr period are compared with independent buoy data and dependent European Remote Sensing Satellite-2 (ERS-2) altimeter wave height data, which have been used in the wave analysis. To apply the triple-collocation method, a fourth, independent dataset is obtained from a wave model hindcast without assimilation of altimeter wave observations. The seasonal dependence of the respective errors is discussed and, while in agreement with the properties of the analysis scheme, the wave height analysis is found to have the smallest error.

In this comparison the altimeter wave height data have been obtained from an average over N individual observations. By comparing model wave height with the altimeter superobservations for different values of N, alternative estimates of altimeter and model error are obtained. There is only agreement with the estimates from the triple collocation when the correlation between individual altimeter observations is taken into account.

The collocation method is also applied to estimate the error in Environmental Satellite (ENVISAT), ERS-2 altimeter, buoy, model first-guess, and analyzed wave heights. It is shown that there is a high correlation between ENVISAT and ERS-2 wave height error, while the quality of ENVISAT altimeter wave height is high.
The Real-Time Data Management System for Argo Profiling Float Observations
Authors: Schmid Claudia , Molinari Robert L. , Sabina Reyna , Daneshzadeh Yeun-Ho , Xia Xiangdong , Forteza Elizabeth , Yang Huiqin
Published: September 2007

Argo is an internationally coordinated program directed at deploying and maintaining an array of 3000 temperature and salinity profiling floats on a global 3° latitude × 3° longitude grid. Argo floats are deployed from research vessels, merchant ships, and aircraft. After launch they sink to a prescribed pressure level (typically 1000–2000 dbar), where most floats remain for 10 days. The floats then return to the surface, collecting temperature and salinity profiles. At the surface they transmit the data to a satellite and sink again to repeat the cycle. As of 10 August 2006 there are 2489 floats reporting data. The International Argo Data Management Team oversees the development and implementation of the data management protocols of Argo. Two types of data systems are active—real time and delayed mode. The real-time system receives the transmissions from the Argo floats, extracts the data, checks their quality, and makes them available to the users. The objective of the real-time system is to provide Argo profiles to the operational and research community within 24 h of their measurement. This requirement makes it necessary to control the quality of the data automatically. The delayed-mode quality control is directed at a more detailed look at the profiles using statistical methods and scientific review of the data. In this paper, the real-time data processing and quality-control methodology is described in detail. Results of the application of these procedures to Argo profiles are described.
Handheld Sun Photometer Measurements from Light Aircraft*
Authors: Porter John N. , Clarke Antony , Reid Jeffrey S. , Reid Elizabeth A. , Shaw Glen , Maring Hal , Kress David
Published: September 2007

Handheld sun photometers are typically used to make aerosol optical depth measurements while on the ground. Various investigators, in unrelated efforts, have used handheld sun photometers to make aerosol optical depth measurements from light aircraft, but the strengths and weakness of this approach have not been characterized until now. While the ease and relatively low cost of an aircraft manual sun photometer are attractive, determining if the sun photometer was correctly pointed at the sun for each measurement is the biggest challenge. This problem can be partially addressed by collecting a large number of measurements at each altitude, then manually removing the largest optical depths (misalignment always results in erroneous larger values). Examples of past aircraft manual sun photometer measurements are demonstrating that it is possible to obtain quantitative measurements if sufficient sun photometer measurements are made at each elevation. In order to improve on manual sun photometer measurements, a small webcam was attached to the side of a Microtops sun photometer, and the Microtops sun photometer was triggered by computer control. By detecting the position of the sun in the webcam image, it is possible to determine whether the sun photometer was pointed at the sun correctly when the aerosol optical depth measurement was made. Unfortunately, it was found that the Microtops sun photometer takes ∼1.1 s to scan over the five wavelength channels. This 1.1-s delay proved to be too long, preventing the proposed approach from working as the aircraft was bouncing around.
Spontaneous Coronary Artery Dissection of the Left Circumflex Artery Causing Cardiac Tamponade and Presenting With Atrial Fibrillation: A Case Report and Review of the Literature
Authors: Hayes Christopher R. , Lewis Debbie
Published: September 2007

Spontaneous coronary artery dissection is rare. When it does occur, it can present in a myriad of ways and can mimic more common clinical scenarios. Undiagnosed it can be fatal. In this article, the authors present a case of coronary artery dissection in a middle aged man presenting as fast atrial fibrillation with hemodynamic compromise. He was unsuccessfully cardioverted and later arrested and died. Postmortem showed a ruptured dissection of the left circumflex artery causing cardiac tamponade and death. Incidence, associations, pathophysiology, investigations, and treatment options are reviewed.
The Clinician-Patient Partnership Paradigm: Outcomes Associated With Physician Communication Behavior
Authors: Clark Noreen M. , Cabana Michael D. , Nan Bin , Gong Z. Molly , Slish Kathryn K. , Birk Nancy A. , Kaciroti Niko
Published: September 2007

Objective: To identify physician communication behaviors associated with perceptions of quality of care and predictive of positive patient outcomes.

Patients and Methods: A total of 452 families seeing 48 pediatricians for a child's asthma participated. Perceptions and health care use were assessed at baseline and after 12 months through interviews and medical records. The measures used were 10 physician communication behaviors and 6 items describing physician's performance, asthma office visits, emergency department visits, and hospitalization.

Results: Positive perceptions of physicians' performance were related to ( P ≤ .05) careful listening, inquiring about at-home management, nonverbal attention, interactive conversation, tailoring short-term goals, and long-term therapeutic plan. Loss in health care use was predicted ( P ≤ .05) by interactive conversation, short-term goals, criteria for decision making, long-term treatment plan, and tailoring according to needs. The use of these techniques did not lengthen the patient visit. A clinician-patient partnership paradigm is provided based on these findings.

Conclusions: The specific clinician communication behaviors predicted reduced health care use and positive perceptions of quality of care.
Knowledge and Use of Music Therapy Among Pediatric Practitioners in Michigan
Authors: Mathur Ambika , Duda Laura , Kamat Deepak M.
Published: September 2007

Objective Increasingly, music therapy is being used, in combination with conventional treatment modalities, as part of the health care treatment plan. The objective of our study was to determine the awareness, knowledge and use of music therapy by members of the Michigan chapter of the American Academy of Pediatrics (Michigan AAP) in their health care practice.

Methods Members of the Michigan AAP were asked to participate in a survey designed to assess their knowledge and use of music therapy in their health care practice.

Results Although the majority of respondents were aware of the use of music therapy in health care settings, very few had referred their own patients for music therapy services.

Conclusion Music therapy is an inexpensive and noninvasive treatment modality being used increasingly, especially to alleviate pain, stress, and anxiety among patients in a variety of conditions. Pediatric practitioners in Michigan, who responded to our survey, expressed a strong interest in learning more about music therapy and learning about ways to incorporate music therapy into their health care practice.
Social Cleavages and the Number of Parties
Authors: Stoll Heather
Published: September 2007

This article explores the issues surrounding the operationalization and measurement of social cleavages in a large- N context from the perspective of the party systems literature. It first highlights the difficulty of measuring the concept, which it argues has impeded hypothesis testing, and suggests strategies for improving upon existing measures. It then demonstrates that the conclusions we draw about well-known hypotheses linking social cleavages to the number of electoral parties in legislative elections depend upon the measure we employ. Hence, the article makes the case that how we measure social cleavages matters.
Home on the Range
Authors: Wyatt Sally , Balmer Brian
Published: September 2007

This article introduces the special issue on middle-range theory in science and technology studies (STS), providing the background to its production and reviewing different notions of “middle.” It begins with Merton's ideas about middle-range theory as a way of moving beyond the production of either descriptions or theories of everything. Instead of seeing the middle as the space between the theoretical imagination and the detailed depiction of everyday practices, the authors outline three ways of thinking about the middle range: as an adjective, the closest to Merton's conception; as a noun, the liminal place between theories, audiences, and levels; and as a verb, a process, a means of making connections across time, discipline, community, and place. A summary of each of the articles in this special issue is provided, preceding a call for further discussion about the role of case studies and the nature of the middle in STS.
Not Another Case Study
Authors: Beaulieu Anne , Scharnhorst Andrea , Wouters Paul
Published: September 2007

This article addresses the need to problematize “cases” in science and technology studies (STS) work, as a middle-range theory issue. The focus is not on any one case study per se, but on why case studies exist and endure in STS. Case studies are part of a specific problematization in the field. We therefore explore relations between motivation for the use of cases (especially ethnographic ones), their constitution, and ways they can be invoked to make particular kinds of arguments in STS. We set out to examine the case as an object that links together research practices, intellectual debates, and programmatic concerns in our own work. Based on our experiences and on this reflection on the links between cases and questions in STS, we propose a number of casemaking strategies that shift and enrich the deployment of ethnographic cases as an epistemic tool in STS.
An Investigation of Fraud in Nonprofit Organizations: Occurrences and Deterrents
Authors: Greenlee Janet , Fischer Mary , Gordon Teresa , Keating Elizabeth
Published: September 2007

Losses due to fraudulent activities are particularly troublesome in the nonprofit sector because they directly reduce resources available to address tax-exempt purposes. The ensuing bad publicity also may reduce contributions and grants in subsequent periods. This article uses data provided by Certified Fraud Examiners to report on the types of fraud they identified in nonprofit organizations and the characteristics of both the victims and the perpetrators of the fraudulent activities. Based on the analysis of the data, the authors suggest ways that fraud losses can be prevented or mitigated. In particular, governing boards are urged to consider important controls in addition to the annual financial statement audit.
The Evaluation Self-Efficacy Scale for Assessing Progress Toward CSWE Accreditation—Related Objectives: A Replication
Authors: Holden Gary , Barker Kathleen , Rosenberg Gary , Onghena Patrick
Published: September 2007

Objective: The Evaluation Self-Efficacy Scale (ESE) is being developed as an outcomes assessment instrument for social work courses focusing on evaluation. Method: This scale, based on social cognitive theory, was pretested, revised, and then used with a final sample of 85 master's-level students in the original study. Using a single-group, pretest-posttest retrospective design, the current study (N = 111) is a direct replication of the original ESE study. Results: In this replication, Cronbach's alphas for the ESE were .95 (pretest), .95 (posttest), and .96 (retrospective pretest). Evidence for the construct validity of the ESE is obtained. Conclusion: The results provide additional evidence supporting the psychometric properties of data obtained using the ESE, suggesting that it may be appropriate for use in educational outcomes assessment in general and accreditation-related research in particular.
LREE distribution patterns in zoned alkali feldspar megacrysts from the
Karkonosze pluton, Bohemian Massif - implications for parental magma
composition
Authors: Słaby E. , Seltmann R. , Kober B. , Müller A. , Galbarczyk-GąSiorowska L. , Jeffries T.
Published: September 2007

The elemental compositions of zoned alkali feldspar megacrysts from the
Karkonosze pluton have been analysed and Pb isotope ratios determined using
LA-ICP-MS, EMPA and TIMS. The results are used to interpret the magmatic
environments within which they crystallized. Growth zones in the megacrysts show
fluctuating trace element patterns that reflect a systematic relationship between
incompatible LREE and compatible Ba. Chemical gradients
between zones in the cores and rims of the megacrysts are not accompanied by
significant variation in initial Pb isotope composition. The nucleation and
crystallization of the megacrysts is interpreted as having occurred in an
environment of magmatic hybridization caused by mixing of mantle and crustal
components in which effective homogenization of the Pb isotope composition
preceded the onset of megacryst growth. The concentrations of
LREE in alkali feldspar zones were used to
reconstruct hypothetical melt compositions. Some of the zones appear to have
crystallized in an homogenous magmatic environment having clear geochemical
affinities with end-member magmas in the Karkonosze pluton, whereas others
crystallized in heterogeneous domains of magma hybridization. With the exception
of Nd, zones crystallized in more homogeneous magma show
LREE fractionation under near-equilibrium
conditions. Trace element abundances of megacrysts grown in dynamic, homogeneous
magmatic environments of the Karkonosze pluton occasionally deviate from the
predicted patterns and show LREE
impoverishment.
Olmiite, CaMn[SiO3(OH)](OH), the Mn-dominant analogue of
poldervaartite, a new mineral species from Kalahari manganese fields (Republic of
South Africa)
Authors: Bonazzi P. , Bindi L. , Medenbach O. , Pagano R. , Lampronti G. I. , Menchetti S.
Published: September 2007

Olmiite, ideally CaMn[SiO3(OH)](OH), is a newly
identified mineral from the N’Chwaning II mine of the Kalahari manganese fields
(Republic of South Africa), which occurs as a product of hydrothermal alteration
associated with poldervaartite, celestine, sturmanite, bultfonteinite and
hematite. The mineral occurs as wheat-sheaf aggregates consisting of pale to
intense reddish pink minute crystals. Olmiite is transparent with vitreous lustre,
and exhibits deep-red fluorescence under short-wave UV-light. The mineral is
brittle, with irregular fracture. Streak is white and Mohs hardness is 5–51/2. No
cleavage was observed. The measured density (pycnometer method) is 3.05(3)
g/cm3. The calculated density is 3.102
g/cm3 or 3.109 g/cm3 using the
unit-cell volume from single-crystal or powder data, respectively. Olmiite is
biaxial positive, with refractive indices α = 1.663(1), β = 1.672(1), γ = 1.694(1)
(589 nm), 2Vmeas = 71.8(1)º, 2Vcalc =
66(8)º. The optical orientation is X = a, Y = c, Z = b and dispersion: r > v,
distinct. Pleochroism is not observed. Chemical analysis by electron microprobe
yielded the chemical formula
(Ca2–xMnxFey)[SiO3(OH)](OH),
with 0.84 ≤ x ≤ 0.86, and y ≤ 0.01. Olmiite is orthorhombic, space group Pbca,
with a = 9.249(3), b = 9.076(9), c = 10.342(9) Å , V = 868(1) Å 3 and Z = 8. The
strongest five powder-diffraction lines [d in Å ,
(I/Io), hkl] are: 4.14, (45), 021; 3.19, (100), 122;
2.807, (35), 311; 2.545 (35), 312; 2.361, (40), 223. Single-crystal structure
refinement (R1 = 2.74% for 1012 observed reflections) showed that the atomic
arrangement of olmiite is similar to that of poldervaartite, with all Mnordered
onthe M2 site. Significant variations in bond distances
and angles are related to the pronounced difference in the Mn content. Olmiite,
therefore, is the Mn-dominant analogue of poldervaartite. The name poldervaartite
should be reserved for samples having Ca dominant at the
M2 site.
Burkeite and hanksite at Copahue, Argentina: the first occurrence of
sulphate-carbonate minerals in a geothermal field
Authors: Mas G. R. , Bengochea L. , Mas L. C.
Published: September 2007

Deposition of two anhydrous sulphate-carbonate minerals, burkeite and
hanksite, around a vapour escape in the pipe of a geothermal well of the Copahue
field in Argentina is described. These minerals usually occur as efflorescences in
saline soils or in continental lacustrine evaporite deposits, but have not been
reported as products from geothermal fluids. Both minerals have been studied by
means of X-ray diffraction, scanning electron microscopy and electron dispersive
energy, and thermo-gravimetric analysis, and have been determined as burkeite,
Na6(CO3)(SO4)2,
and hanksite,
KNa22(SO4)9(CO3)2Cl.
Highly penetrant myeloproliferative disease in the Ts65Dn mouse model of Down syndrome
Authors: Kirsammer Gina , Jilani Sarah , Liu Hui , Davis Elizabeth , Gurbuxani Sandeep , Le Beau Michelle M. , Crispino John D.
Published: September 2007

Children with Down syndrome (DS) display macrocytosis, thrombocytosis, and a 500-fold increased risk of developing megakaryocytic leukemia; however, the specific effects of trisomy 21 on hematopoiesis remain poorly defined. To study this question, we analyzed blood cell development in the Ts65Dn mouse model of DS. Ts65Dn mice are trisomic for 104 orthologs of Hsa21 genes and are the most widely used mouse model for DS. We discovered that Ts65Dn mice display persistent macrocytosis and develop a myeloproliferative disease (MPD) characterized by profound thrombocytosis, megakaryocyte hyperplasia, dysplastic megakaryocyte morphology, and myelofibrosis. In addition, these animals bear distorted hematopoietic stem and myeloid progenitor cell compartments compared with euploid control littermates. Of the 104 trisomic genes in Ts65Dn mice, Aml1/Runx1 attracts considerable attention as a candidate oncogene in DS–acute megakaryoblastic leukemia (DS-AMKL). To determine whether trisomy for Aml1/Runx1 is essential for MPD, we restored disomy at the Aml1/Runx1 locus in the Ts65Dn strain. Surprisingly, trisomy for Aml1/Runx1 is not required for megakaryocyte hyperplasia and myelofibrosis, suggesting that trisomy for one or more of the remaining genes can promote this disease. Our studies demonstrate the potential of DS mouse models to improve our understanding of chromosome 21 gene dosage effects in human hematologic malignancies.
Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress
Authors: Shim Kyuhwan , Anderson Patricia J. , Tuley Elodee A. , Wiswall Erin , Evan Sadler J.
Published: September 2007

Endothelial cells secrete prothrombotic ultralarge von Willebrand factor (VWF) multimers, and the metalloprotease ADAMTS13 cleaves them into smaller, less dangerous multimers. This reaction is stimulated by tensile force applied to the VWF substrate, which may occur on cell surfaces or in the circulating blood. The cleavage of soluble VWF by ADAMTS13 was accelerated dramatically by a combination of platelets and fluid shear stress applied in a cone-plate viscometer. Platelet-dependent cleavage of VWF was blocked by an anti-GPIbα monoclonal antibody or by a recombinant soluble fragment of GPIbα that prevents platelet-VWF binding. Multimeric gel analysis showed that shear and platelet-dependent cleavage consumed large VWF multimers. Therefore, ADAMTS13 preferentially acts on platelet-VWF complexes under fluid shear stress. This reaction is likely to account for a majority of VWF proteolysis after secretion and to determine the steady-state size distribution of circulating VWF multimers in vivo.
Inhibition of tissue factor signaling suppresses tumor growth
Authors: Versteeg Henri H. , Schaffner Florence , Kerver Marjolein , Petersen Helle H. , Ahamed Jasimuddin , Felding-Habermann Brunhilde , Takada Yoshikazu , Mueller Barbara M. , Ruf Wolfram
Published: September 2007

Coagulation activation by tissue factor (TF) is implicated in cancer progression, cancer-associated thrombosis and metastasis. The role of direct TF signaling pathways in cancer, however, remains incompletely understood. Here we address how TF contributes to primary tumor growth by using a unique pair of isotype-matched antibodies that inhibit either coagulation (monoclonal antibody [Mab]-5G9) or direct signaling (Mab-10H10). We demonstrate that the inhibitory antibody of direct TF-VIIa signaling not only blocks TF-VIIa mediated activation of PAR2, but also disrupts the interaction of TF with integrins. In epithelial and TF-expressing endothelial cells, association of TF with β1 integrins is regulated by TF extracellular ligand binding and independent of PAR2 signaling or proteolytic activity of VIIa. In contrast, α3β1 integrin association of TF is constitutive in breast cancer cells and blocked by Mab-10H10 but not by Mab-5G9. Mab-5G9 has antitumor activity in vivo, but we show here that Mab-10H10 is at least as effective in suppressing human xenograft tumors in 2 different models. Breast tumor growth was also attenuated by blocking PAR2 signaling. These results show that tumor cell TF-PAR2 signaling is crucial for tumor growth and suggest that anti-TF strategies can be applied in cancer therapy with minor impairment of TF-dependent hemostatic pathways.
Forced expiratory volume in one second: not just a lung function test but a marker of premature death from all causes
Authors: Young R. P. , Hopkins R. , Eaton T. E.
Published: September 2007

The clinical utility of spirometric screening of asymptomatic smokers for early signs of air flow limitation has recently come under review. The current authors propose that reduced forced expiratory volume in one second (FEV1) is more than a measure of airflow limitation, but a marker of premature death with broad utility in assessing baseline risk of chronic obstructive pulmonary disease (COPD), lung cancer, coronary artery disease and stroke, collectively accounting for 70–80% of premature death in smokers.

Reduced FEV1identifies undiagnosed COPD, has comparable utility to that of serum cholesterol in assessing cardiovascular risk and defines those smokers at greatest risk of lung cancer. As such, reduced FEV1should be considered a marker that identifies smokers at greatest need of medical intervention.

Smoking cessation has been shown to attenuate FEV1decline and, if achieved before the age of 45–50 yrs, may not only preserve FEV1within normal values but substantially reduce cardiorespiratory complications of smoking.

Recent findings suggest inhaled drugs (bronchodilators and corticosteroids), and possibly statins, may be effective in reducing morbidity and mortality in patients with chronic obstructive pulmonary disease. The current authors propose that spirometry has broad utility in identifying smokers who are at greatest risk of cardiorespiratory complications and greatest benefit from targeted preventive strategies, such as smoking cessation, prioritised screening and effective pharmacotherapy.
Congenital cystic adenomatoid malformation presenting as in-flight systemic air embolisation
Authors: Belcher E. , Lawson M. H. , Nicholson A. G. , Davison A. , Goldstraw P.
Published: September 2007

Congenital cystic adenomatoid malformations (CCAMs) are rarely diagnosed in adulthood. The present case study reports a case of a CCAM presenting as a cerebral air embolus during an international flight.

In the present case, supportive therapy resulted in a full recovery. The patient later underwent elective excision of the pulmonary malformation.

Since the overall mortality of in-flight cerebral air embolisation is high, patients with such asymptomatic cysts should be considered for elective surgery.
Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer
Authors: Villiard Éric , Brinkmann Henner , Moiseeva Olga , Mallette Frédérick A , Ferbeyre Gerardo , Roy Stéphane
Published: September 2007

Background

Urodele amphibians like the axolotl are unique among vertebrates in their ability to regenerate and their resistance to develop cancers. It is unknown whether these traits are linked at the molecular level.

Results

Blocking p53 signaling in axolotls using the p53 inhibitor, pifithrin-α, inhibited limb regeneration and the expression of p53 target genes such as Mdm2 and Gadd45, suggesting a link between tumor suppression and regeneration. To understand this relationship we cloned the p53 gene from axolotl. When comparing its sequence with p53 from other organisms, and more specifically human we observed multiple amino acids changes found in human tumors. Phylogenetic analysis of p53 protein sequences from various species is in general agreement with standard vertebrate phylogeny; however, both mice-like rodents and teleost fishes are fast evolving. This leads to long branch attraction resulting in an artefactual basal emergence of these groups in the phylogenetic tree. It is tempting to assume a correlation between certain life style traits (e.g. lifespan) and the evolutionary rate of the corresponding p53 sequences. Functional assays of the axolotl p53 in human or axolotl cells using p53 promoter reporters demonstrated a temperature sensitivity (ts), which was further confirmed by performing colony assays at 37°C. In addition, axolotl p53 was capable of efficient transactivation at the Hmd2 promoter but has moderate activity at the p21 promoter. Endogenous axolotl p53 was activated following UV irradiation (100 j/m2) or treatment with an alkylating agent as measured using serine 15 phosphorylation and the expression of the endogenous p53 target Gadd45.

Conclusion

Urodele p53 may play a role in regeneration and has evolved to contain multiple amino acid changes predicted to render the human protein defective in tumor suppression. Some of these mutations were probably selected to maintain p53 activity at low temperature. However, other significant changes in the axolotl proteins may play more subtle roles on p53 functions, including DNA binding and promoter specificity and could represent useful adaptations to ensure p53 activity and tumor suppression in animals able to regenerate or subject to large variations in oxygen levels or temperature.
Phase III Randomized Trial of Intravenous Cisplatin Plus a 24- or 96-Hour Infusion of Paclitaxel in Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: Spriggs David R. , Brady Mark F. , Vaccarello Luis , Clarke-Pearson Daniel L. , Burger Robert A. , Mannel Robert , Boggess John F. , Lee Roger B. , Hanly Mark
Published: September 2007

Purpose

This study was undertaken to assess if prolonged paclitaxel administration in combination with cisplatin improves overall survival (OS) in epithelial ovarian cancer (EOC).

Patients and Methods

Eligible patients with suboptimal stage III or IV EOC, fallopian tube, or primary peritoneal cancer were randomly allocated to receive six cycles of cisplatin 75 mg/m2 and either paclitaxel 135 mg/m2 during 24 hours (arm 1) or paclitaxel 120 mg/m2 during 96 hours (arm 2).

Results

Planned accrual was 324 patients; 293 were enrolled before the study was closed as a result of a scheduled interim futility analysis. There were 13 ineligible patients; thus, 140 patients in each arm were assessable. In arm 1, 80% of patients completed all six cycles compared with 83% of patients in arm 2. Grade 4 granulocytopenia was more common in arm 1 (79% v 54%; P < .001) whereas grade 3 or worse anemia was more severe in arm 2 (6% v 18%; P < .003). The median progression-free survival was 1.03 years for arm 1 versus 1.05 years for arm 2. The median OS was 2.49 and 2.54 years for arms 1 and 2, respectively. There have been 237 reported deaths. The relative death rate was approximately 12% greater in arm 2 (hazard ratio, 1.12; 95% CI, 0.860 to 1.45).

Conclusion

Patients with advanced EOC have a relatively poor prognosis. The results of treatment with cisplatin and paclitaxel are not significantly improved by prolonging the paclitaxel infusion from 24 to 96 hours.
Pharmacogenomic Strategies Provide a Rational Approach to the Treatment of Cisplatin-Resistant Patients With Advanced Cancer
Authors: Hsu David S. , Balakumaran Bala S. , Acharya Chaitanya R. , Vlahovic Vanja , Walters Kelli S. , Garman Katherine , Anders Carey , Riedel Richard F. , Lancaster Johnathan , Harpole David , Dressman Holly K. , Nevins Joseph R. , Febbo Phillip G. , Potti Anil
Published: September 2007

Purpose

Standard treatment for advanced non–small-cell lung cancer (NSCLC) includes the use of a platinum-based chemotherapy regimen. However, response rates are highly variable. Newer agents, such as pemetrexed, have shown significant activity as second-line therapy and are currently being evaluated in the front-line setting. We utilized a genomic strategy to develop signatures predictive of chemotherapeutic response to both cisplatin and pemetrexed to provide a rational approach to effective individualized medicine.

Methods

Using in vitro drug sensitivity data, coupled with microarray data, we developed gene expression signatures predicting sensitivity to cisplatin and pemetrexed. Signatures were validated with response data from 32 independent ovarian and lung cancer cell lines as well as 59 samples from patients previously treated with cisplatin.

Results

Genomic-derived signatures of cisplatin and pemetrexed sensitivity were shown to accurately predict sensitivity in vitro and, in the case of cisplatin, to predict treatment response in patients treated with cisplatin. The accuracy of the cisplatin predictor, based on available clinical data, was 83.1% (sensitivity, 100%; specificity 57%; positive predictive value, 78%; negative predictive value, 100%). Interestingly, an inverse correlation was seen between in vitro cisplatin and pemetrexed sensitivity, and importantly, between the likelihood of cisplatin and pemetrexed response in patients.

Conclusion

The use of genomic predictors of response to cisplatin and pemetrexed can be incorporated into strategies to optimize therapy for advanced solid tumors.
Patients With Curative Resection of cT3-4 Rectal Cancer After Preoperative Radiotherapy or Radiochemotherapy: Does Anybody Benefit From Adjuvant Fluorouracil-Based Chemotherapy? A Trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group
Authors: Collette Laurence , Bosset Jean-Francois , den Dulk Marcel , Nguyen France , Mineur Laurent , Maingon Philippe , Radosevic-Jelic Ljiljana , Piérart Marianne , Calais Gilles
Published: September 2007

Purpose

European Organisation for Research and Treatment of Cancer (EORTC) trial 22921 compared adjuvant fluorouracil-based chemotherapy (CT) to no adjuvant treatment in a 2 × 2 factorial trial with randomization for preoperative (chemo)radiotherapy in patients with resectable T3-4 rectal cancer. The results showed no significant impact of adjuvant CT on progression-free or overall survival, although a difference seemed to emerge at approximately, respectively, 2 and 5 years after the start of preoperative treatment. We further explored the data with the aim of refining our understanding of the long-term results.

Patients and Methods

Data of 785 of the 1,011 randomly assigned patients who whose disease was M0 at curative surgery were used. Using meta-analytic methods, we investigated the homogeneity of the effect of adjuvant CT on the time to relapse or death after surgery (disease-free survival [DFS]) and survival in patient subgroups.

Results

Although there was no statistically significant impact of adjuvant CT on DFS for the whole group (P > .5), the treatment effect differed significantly between the ypT0-2 and the ypT3-4 patients (heterogeneity P = .009): only the ypT0-2 patients seemed to benefit from adjuvant CT (P = .011). The same pattern was observed for overall survival.

Conclusion

Exploratory analyses suggest that only good-prognosis patients (ypT0-2) benefit from adjuvant CT. This could explain why, in the whole group, the progression-free and overall survival diverged only after the poor-prognosis patients (ypT3-4) had experienced treatment failure. Patients in whom no downstaging was achieved did not benefit. This also suggests that the same prognostic factors may drive both tumor sensitivity for the primary treatment and long-term clinical benefit from further adjuvant CT.
Hormone-Induced Expression of Tumor Necrosis Factor α-Converting Enzyme/A Disintegrin and Metalloprotease-17 Impacts Porcine Cumulus Cell Oocyte Complex Expansion and Meiotic Maturation via Ligand Activation of the Epidermal Growth Factor Receptor
Authors: Yamashita Yasuhisa , Kawashima Ikkou , Yanai Yoshiari , Nishibori Masahide , Richards JoAnne S. , Shimada Masayuki
Published: September 2007

The epidermal growth factor (EGF)-like growth factors, amphiregulin (AREG) and epiregulin (EREG), are expressed in murine cumulus oocyte complexes (COCs) where they impact the function of cumulus cells and oocyte maturation during LH-mediated ovulation. Because TNFα-converting enzyme (TACE)/a disintegrin and metalloprotease-17 (ADAM17) is essential for ectodomain shedding of AREG and EREG from the surface of other cell types, the expression and function of TACE/ADAM17 was analyzed in a porcine COC culture system in which FSH- and LH-mediated expansion and oocyte meiotic maturation have been well characterized and shown to occur between 20 and 40 h. In this model, Areg, Ereg, and Tace/Adam17 mRNAs increased significantly with maximal levels observed between 5 and 20 h of culture with FSH plus LH. TACE/ADAM17 protein and protease activity were up-regulated markedly at 10 h and maintained to 40 h. Treatment of COCs with the TACE/ADAM17-selective inhibitor TNFα-processing inhibitor-2 (TAPI-2) significantly suppressed in a time-dependent manner downstream targets of EGF receptor activation such as ERK1/2 phosphorylation, Ptgs2, Has2, and Tnfaip6 mRNA expression, hormone-induced COC expansion, and meiotic maturation of the oocytes. Addition of EGF to COCs cultured in the presence of FSH/LH reversed the inhibitory effects of TAPI-2 on these ovulation-related processes. Gonadotropin-induced phosphorylation of ERK1/2 was also inhibited in rat granulosa cells treated with TAPI-2 or after transfection with Tace/Adam17 small interfering RNA. Induced expression of Tnfaip6 mRNA was also reduced by Tace/Adam17 small interfering RNA. Thus, TACE/ADAM17 is induced and the activity is involved in porcine COC expansion as well as oocyte meiotic maturation through the activation of EGF receptor in cumulus cells.
Molecular Cloning and Characterization of Prostaglandin (PG) Transporter in Ovine Endometrium: Role for Multiple Cell Signaling Pathways in Transport of PGF2α
Authors: Banu S. K. , Lee J. , Satterfield M. C. , Spencer T. E. , Bazer F. W. , Arosh J. A.
Published: September 2007

In ruminants, endometrial prostaglandin F2α (PGF2α) is the luteolytic hormone. Cellular transport of PGF2α in the uterine endometrium is critical for regulation of the estrous cycle. Molecular mechanisms responsible for control of PGF2α transport in endometrium during luteolysis are largely unknown. In the present study, we characterized the prostaglandin transporter (PGT) in ovine endometrium. Ovine PGT cDNA consists of 1935 nucleotides that encode 644 amino acids. In ovine endometria, PGT is highly expressed during the period of luteolysis, between d 14 and 16 of the estrous cycle, in luminal and glandular epithelia. Pharmacological and genomic inhibition of PGT indicates that it is responsible for influx and efflux of PGF2α in ovine endometrial epithelial cells. Inhibition of PGT during the period of luteolysis prevents the release of oxytocin-induced PGF2α pulses, and maintains functional corpus luteum and its secretion of progesterone. In ovine endometrial epithelial cells, protein kinase A and protein kinase C pathways are involved in regulating the influx of PGF2α, whereas epidermal growth factor receptor pathways are implicated in regulation of influx and efflux of PGF2α. The ERK1/2 pathway is associated with efflux of PGF2α, whereas Jun-amino-terminal kinase/stress-activated protein kinase pathways are involved in both efflux and influx of PGF2α. Phosphatidylinositol 3-kinase pathways are not involved in either influx or efflux of PGF2α in ovine endometrial epithelial cells. These are the first results to demonstrate a functional role for PGT in regulation of PGF2α efflux and influx in ovine endometrial cells that influence luteolytic mechanisms in ruminants.
Genome-Wide Identification of Estrogen Receptor α-Binding Sites in Mouse Liver
Authors: Gao Hui , Fält Susann , Sandelin Albin , Gustafsson Jan-Åke , Dahlman-Wright Karin
Published: September 2007

We report the genome-wide identification of estrogen receptor α (ERα)-binding regions in mouse liver using a combination of chromatin immunoprecipitation and tiled microarrays that cover all nonrepetitive sequences in the mouse genome. This analysis identified 5568 ERα-binding regions. In agreement with what has previously been reported for human cell lines, many ERα-binding regions are located far away from transcription start sites; approximately 40% of ERα-binding regions are located within 10 kb of annotated transcription start sites. Almost 50% of ERα-binding regions overlap genes. The majority of ERα-binding regions lie in regions that are evolutionarily conserved between human and mouse. Motif-finding algorithms identified the estrogen response element, and variants thereof, together with binding sites for activator protein 1, basic-helix-loop-helix proteins, ETS proteins, and Forkhead proteins as the most common motifs present in identified ERα-binding regions. To correlate ERα binding to the promoter of specific genes, with changes in expression levels of the corresponding mRNAs, expression levels of selected mRNAs were assayed in livers 2, 4, and 6 h after treatment with ERα-selective agonist propyl pyrazole triol. Five of these eight selected genes, Shp, Stat3, Pdgds, Pck1, and Pdk4, all responded to propyl pyrazole triol after 4 h treatment. These results extend our previous studies using gene expression profiling to characterize estrogen signaling in mouse liver, by characterizing the first step in this signaling cascade, the binding of ERα to DNA in intact chromatin.
Pharmaceutical applications for catanionic mixtures
Authors: Bramer Tobias , Dew Noel , Edsman Katarina
Published: September 2007

Mixtures of oppositely charged surfactants, so called catanionic mixtures, are a growing area of research. These mixtures have been shown to form several different types of surfactant aggregates, such as micelles of various forms and sizes, and lamellar structures, such as vesicles. In this review, a short introduction to the field of catanionic mixtures is presented and the pharmaceutical possibilities offered by such mixtures are reviewed. There are several interesting ideas on how to apply catanionic mixtures to improve the delivery of, for example, drug compounds and DNA, or for HIV treatment.
Development and in-vivo evaluation of insulin-loaded chitosan phthalate microspheres for oral delivery
Authors: Ubaidulla Udhumansha , Khar Roop Kishan , Ahmed Farhan Jalees , Panda Amulya Kumar
Published: September 2007

Novel chitosan phthalate microspheres containing insulin were prepared by emulsion cross-linking technique. The feasibility of these microspheres as oral insulin delivery carriers was evaluated. The pH-responsive release behaviour of insulin from microspheres was analysed. The ability of chitosan phthalate-insulin microspheres to enhance intestinal absorption and improve the relative pharmacological availability of insulin was investigated by monitoring the plasma glucose and insulin level of streptozotocin-induced diabetic rats after oral administration of microspheres at insulin dose of 20 IU kg−1. In simulated gastric fluid (pH 2.0), insulin release from the microspheres was very slow. However, as the pH of the medium was changed to simulated intestinal fluid (pH 7.4), a rapid release of insulin occurred. The relative pharmacological efficacy for chitosan phthalate microspheres (18.66 ± 3.84%) was almost four-fold higher than the efficacy of the chitosan phthalate-insulin solution administration (4.08 ± 1.52%). Chitosan phthalate microspheres sustained the plasma glucose at pre-diabetic level for at least 16 h. These findings suggest that the microsphere is a promising carrier as oral insulin delivery system.
Suppressive activity of fexofenadine hydrochloride on nitric oxide production in-vitro and in-vivo
Authors: Asano Kazuhito , Kanai Ken-ichi , Furuta Atsuko , Furuya Ayako , Suzaki Harumi , Hisamitsu Tadashi
Published: September 2007

The aim of this study was to examine the effect of fexofenadine hydrochloride (FEX), a histamine H1- receptor antagonist, on nitric oxide (NO) production in-vitro and in-vivo. Nasal fibroblasts (5 × 105 cells per mL) were stimulated with 25 ng mL−1 tumour necrosis factor-α in the presence of various concentrations of FEX. NO levels in 24-h-culture supernatants were measured by the Griess method and levels of inducible nitric oxide synthase (iNOS) mRNA levels in 12-h-cultured cells were measured by ELISA. FEX at more than 0.5 μg mL−1 suppressed NO production from fibroblasts by inhibiting expression of iNOS mRNA. We also examined whether FEX could suppress NO production induced by lipopolysaccharide (LPS) stimulation in-vivo. BALB/c mice were treated with 5.0 mg kg−1 LPS i.p. after daily oral doses of FEX, 1.0 mg kg−1, for 1–3 weeks. Plasma was obtained 6 h later and NO levels measured by the Griess method. Expression of iNOS mRNA in lung tissues was measured by ELISA 6h after LPS injection. Oral administration of FEX for 2 and 3 weeks, but not 1 week, significantly suppressed NO levels in plasma through the inhibition of iNOS mRNA expression, which were enhanced by LPS stimulation. These results suggest that the attenuating effect of FEX on NO production may be of therapeutic benefit in allergic diseases.