bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrin αvβ3-Targeted IRDye 800CW Near-Infrared Imaging of Glioblastoma
Authors: Huang Ruimin , Vider Jelena , Kovar Joy L. , Olive D. Michael , Mellinghoff Ingo K. , Mayer-Kuckuk Philipp , Kircher Moritz F. , Blasberg Ronald G.
Published: August 2012

Purpose: Integrin αvβ3 plays an important role in tumor angiogenesis, growth, and metastasis. We have tested a targeted probe to visualize integrin receptor expression in glioblastomas using near-infrared fluorescent (NIRF) imaging.

Experimental design: A transgenic glioblastoma mouse model (RCAS-PDGF-driven/tv-a glioblastoma, which mimics the infiltrative growth pattern of human glioblastomas) and two human orthotopic glioblastoma models (U-87 MG with high integrin β3 expression and TS543 with low integrin β3 expression) were studied. An integrin-targeting NIRF probe, IRDye 800CW-cyclic-RGD peptide (IRDye 800CW-RGD), was tested by in vivo and ex vivo NIRF imaging.

Results: We show that the IRDye 800CW-RGD peptide: (i) specifically binds to integrin receptors; (ii) is selectively localized to glioblastoma tissue with overexpressed integrin receptors and is retained over prolonged periods of time; (iii) is associated with minimal autofluorescence and photobleaching because of imaging at 800 nm; (iv) provides delineation of tumor tissue with high precision because of a high tumor-to-normal brain fluorescence ratio (79.7 ± 6.9, 31.2 ± 2.8, and 16.3 ± 1.3) in the U-87 MG, RCAS-PDGF, and TS543 models, respectively; P < 0.01); and (v) enables fluorescence-guided glioblastoma resection. Importantly, small foci of residual fluorescence were observed after resection was completed using white light imaging alone, and these fluorescent foci were shown to represent residual tumor tissue by histology.

Conclusions: NIRF imaging with the IRDye 800CW-RGD probe provides a simple, rapid, low-cost, nonradioactive, and highly translatable approach for improved intraoperative glioblastoma visualization and resection. It also has the potential to serve as an imaging platform for noninvasive cancer detection and drug efficacy evaluation studies. Clin Cancer Res; 18(20); 5731–40. ©2012 AACR.
Publication and Reporting Conduct for Pharmacodynamic Analyses of Tumor Tissue in Early-Phase Oncology Trials
Authors: Freeman Georgina A. , Kimmelman Jonathan
Published: August 2012

Purpose: In principle, nondiagnostic biopsies for pharmacodynamic (PD) studies are carried out to inform decision-making in drug development. Because such procedures have no therapeutic value, their ethical justification requires that results be published. We aimed to assess the frequency of nonpublication of PD data in early phase cancer trials and to identify factors that prevent full publication of data.

Methods: We identified a sample of early-phase cancer trials containing invasive nondiagnostic tissue procurement for PD analysis from American Society of Clinical Oncologyand American Association for Cancer Research meeting abstracts published between 1995 and 2005. These trials were followed to publication to determine frequency of nonpublication of PD data. Corresponding authors on early-phase cancer trials using invasive nondiagnostic research procedures were also surveyed to identify factors preventing full publication of PD data.

Results: In a sample of 90 trials, 22.2% (20 trials) resulted in no trial publication. Of published trials expected to contain PD reports, 16 (17.8%) did not include any PD data, and 21 (23.3%) reported incomplete PD data. We surveyed 92 authors; nonpublication was regarded as a frequent occurrence, and the most commonly cited barrier to full publication of PD data was strategic considerations in publication (58.8% of responding authors).

Conclusions: Our results suggest ways that investigators, study planners, and reviewers can improve the burden/knowledge value balance in PD studies. Clin Cancer Res; 18(23); 6478–84. ©2012 AACR.
Genomic Estimates of Aneuploid Content in Glioblastoma Multiforme and Improved Classification
Authors: Li Bo , Senbabaoglu Yasin , Peng Weiping , Yang Min-Lee , Xu Jishu , Li Jun Z.
Published: August 2012

Purpose: Accurate classification of glioblastoma multiforme (GBM) is crucial for understanding its biologic diversity and informing diagnosis and treatment. The Cancer Genome Atlas (TCGA) project identified four GBM classes using gene expression data and separately identified three classes using methylation data. We sought to integrate multiple data types in GBM classification, understand biologic features of the newly defined subtypes, and reconcile with prior studies.

Experimental Design: We used allele-specific copy number data to estimate the aneuploid content of each tumor and incorporated this measure of intratumor heterogeneity in class discovery. We estimated the potential cell of origin of individual subtypes and the euploid and aneuploid fractions using reference datasets of known neuronal cell types.

Results: There exists an unexpected correlation between aneuploid content and the observed among-tumor diversity of expression patterns. Joint use of DNA and mRNA data in ab initio class discovery revealed a distinct group that resembles the Proneural subtype described in a separate study and the glioma-CpG island methylator phenotype (G-CIMP+) class based on methylation data. Three additional subtypes, Classical, Proliferative, and Mesenchymal, were also identified and revised the assignment for many samples. The revision showed stronger differences in patient outcome and clearer cell type–specific signatures. Mesenchymal GBMs had higher euploid content, potentially contributed by microglia/macrophage infiltration.

Conclusion: We clarified the confusion about the “Proneural” subtype that was defined differently in different prior studies. The ability to infer within-tumor heterogeneity improved class discovery, leading to new subtypes that are closer to the fundamental biology of GBM. Clin Cancer Res; 18(20); 5595–605. ©2012 AACR.
Variants on a Theme: A Biomarker of Crizotinib Response in ALK-Positive Non–Small Cell Lung Cancer?
Authors: Crystal Adam S. , Shaw Alice T.
Published: August 2012

Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 5% of non–small cell lung carcinoma patients and confer sensitivity to ALK inhibitors such as crizotinib. The particular ALK fusion expressed may have an impact on protein stability and sensitivity to crizotinib, and this may underlie the heterogeneity in responses observed in the clinic. Clin Cancer Res; 18(17); 4479–81. ©2012 AACR.
Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer
Authors: Juvekar Ashish , Burga Laura N. , Hu Hai , Lunsford Elaine P. , Ibrahim Yasir H. , Balmañà Judith , Rajendran Anbazhagan , Papa Antonella , Spencer Katherine , Lyssiotis Costas A. , Nardella Caterina , Pandolfi Pier Paolo , Baselga José , Scully Ralph , Asara John M. , Cantley Lewis C. , Wulf Gerburg M.
Published: August 2012

There is a need to improve treatments for metastatic breast cancer. Here, we show the activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in a MMTV-CreBrca1f/fTrp53+/− mouse model of breast cancer. When treated with the pan-class IA PI3K inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation, and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK pathway at the “pushing margin.” Surprisingly, PI3K inhibition increased indicators of DNA damage, poly-ADP-ribosylation (PAR), and γ-H2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. The PARP inhibitor olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and olaparib delayed tumor doubling to more than 70 days in the mouse model and more than 50 days in xenotransplants from human BRCA1-related tumors, suggesting that combined PI3K and PARP inhibition might be an effective treatment of BRCA1-related tumors.

Significance: Current treatment options for triple-negative breast cancer are limited to chemotherapeutic regimens that have considerable toxicity and are not curative. We report here that the combination of a PI3K inhibitor with a PARP inhibitor provides in vivo synergy for treatment of an endogenous mouse model for BRCA1-related breast cancers, making this a candidate combination to be tested in human clinical trials. Cancer Discov; 2(11); 1048–63. ©2012 AACR.

Read the Commentary on this article by Rehman et al., p. 982.

This article is highlighted in the In This Issue feature, p. 961
Improved Dexterity after Chronic Electrical Stimulation of the Motor Cortex for Central Pain: A Special Relevance for Thalamic Syndrome
Authors: Nuti Christophe , Vassal François , Mertens Patrick , Lemaire Jean-Jacques , Magnin Michel , Peyron Roland
Published: August 2012

Objectives: To demonstrate that motor cortex stimulation (MCS) could improve motor function in patients with neuropathic pain. Methods: In this prospective clinical study of 38 patients referred for MCS as treatment for their neuropathic pain, we collected any declaration of improvement in motor performance that could be attributed to MCS. Results: Ten patients (26%) declared a benefit in their motor function. Eight presented objective evidence of recovered dexterity for rapid alternating movements. A minor proportion had improvement in dystonic posture (n = 2), but none had detectable increased motor strength or tonus changes. Overall, 73% of the patients with limb ataxia declared a benefit after MCS. In 6 out of 10 patients (60%), the anatomic lesion responsible for pain was restricted to the lateral aspect of the thalamus. All of them had either clinical or electrophysiological evidence of lemniscal dysfunction (proprioceptive ataxia). No correlation was found between the scores of pain relief and the modification of motor status. The correlation between thalamic lesions and benefits in motor performance was significant (Fisher’s exact test, two-tailed, p = 0.0017). Conclusions: Up to 26% of patients estimated that MCS improved their motor outcome through recovered dexterity and in cases of lateral thalamic lesions.
Long-Term Outcome of Anterior Thalamic Nucleus Stimulation for Intractable Epilepsy
Authors: Lee Kyung Jin , Shon Young Min , Cho Chul Bum
Published: August 2012

Background: Many patients with epilepsy have persistent seizures despite treatment with maximal antiepileptic drug therapy and are not candidates for resective brain surgery. Objectives: We investigated the effectiveness of seizure reduction after anterior thalamic nucleus (ATN) stimulation in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. Methods: Patients included in this study had poorly controlled seizures, despite anticonvulsant medication, and were not candidates for surgical resection of an identifiable seizure focus. Fifteen patients with medically refractory epilepsy underwent the placement of bilateral DBS electrodes in the anterior thalamus. The seizure frequency was monitored and compared with the preimplantation baseline. Results: The treatment demonstrated a statistically significant decrease in the seizure frequency, with a mean reduction of 70.4% (mean follow-up, 27 months). Two of the patients had a remarkable reduction of seizure frequency. Conclusion: It seems to be important that the short-term outcome of ATN DBS reflects the long-term outcome directly. The correlation between the seizure type, characteristics and anticonvulsant effects of ATN DBS did not exhibit significance because of the small number of cases. Therefore, a longer-term follow-up with a larger group of patients is required to fully evaluate the safety and effectiveness of this treatment modality.
DREZotomy in the Treatment of Cancer Pain: A Review
Authors: Gadgil Nisha , Viswanathan Ashwin
Published: August 2012

Background: Cancer-related pain is a common problem that may be intractable by medical and neuromodulatory treatment. The dorsal root entry zone (DREZ) is a hyperactive focus in neuropathic pain syndromes, and DREZotomy has been used in selective cases of neuropathic cancer pain. Objective: The aim of this study was to describe the technique of spinal DREZotomy in the treatment of cancer pain and review the relevant published literature. Methods: A PubMed database search for ‘DREZ’, ‘dorsal root entry zone’ and ‘cancer’, and a search of the references of these manuscripts, was undertaken. Results: 14 papers were identified and reviewed that described a total of 123 patients with cancer pain or radiation-induced pain who have been treated with DREZotomy. Though heterogeneous, these studies reported an overall favorable outcome in carefully selected patients with topographically limited pain syndromes. Conclusion: For patients with well-localized neuropathic cancer pain intractable to medical and first-line surgical management, DREZotomy is a viable treatment option. Further prospective studies are needed to evaluate the outcomes of this procedure.
A Narrative History of the International Society for Psychiatric Surgery: 1970–1983
Authors: Lipsman Nir , Meyerson Björn A. , Lozano Andres M.
Published: August 2012

In order to reconcile the present resurgence of psychiatric neurosurgery with the not-too-distant historic transgressions in the field, one needs to examine the era of transition from crude art to regulated science. In large part, this transition took place in the 1970s with the continued development and widespread acceptance of stereotactic techniques in functional neurosurgery and several hard-fought ideological and academic victories by proponents of the much-maligned field. Established in 1970, the International Society for Psychiatric Surgery (ISPS) sought to gather like-minded surgeons, psychiatrists and other neuroscientists to counter the rising pressure from special interest groups, as well as some in the public and medical realm, who attempted to abolish all forms of surgical management of psychiatric disease. We reviewed the archives of the ISPS, including letters from its founding members and active participants, conference proceedings and minutes from organizational meetings, from throughout its existence from 1970 to 1983. The archives provide a unique insight into the organization and objectives of the society that kept psychiatric surgery alive in the face of persistent and staunch opposition. We also outline the lessons that current and future functional neurosurgeons can learn from the ISPS, whose key figures, structure and communication, in the non-electronic era, were instrumental for the survival of psychiatric surgery during that critical period.
A Simple Echocardiographic Prediction Rule for Hemodynamics in Pulmonary Hypertension
Authors: Opotowsky Alexander R. , Ojeda Jason , Rogers Frances , Prasanna Vikram , Clair Mathieu , Moko Lilamarie , Vaidya Anjali , Afilalo Jonathan , Forfia Paul R.
Published: August 2012

Background—

Pulmonary hypertension (PH) has diverse causes with heterogeneous physiology compelling distinct management. Differentiating patients with primarily elevated pulmonary vascular resistance (PVR) from those with PH predominantly because of elevated left-sided filling pressure is critical.

Methods and Results—

We reviewed hemodynamics, echocardiography, and clinical data for 108 patients seen at a referral PH clinic with transthoracic echocardiogram and right heart catheterization within 1 year. We derived a simple echocardiographic prediction rule to allow hemodynamic differentiation of PH attributed to pulmonary vascular disease (PH
PVD
, defined as pulmonary artery wedge pressure [PAWP]≤15 mm Hg and PVR>3 WU). Age averaged 61.3±14.8 years, μPAWP and PVR were 16.4±7.1 mm Hg and 6.3±4.0 WU, respectively, and 52 (48.1%) patients fulfilled PH
PVD
hemodynamic criteria. The derived prediction rule ranged from –2 to +2 with higher scores suggesting higher probability of PH
PVD
: +1 point for left atrial anterior–posterior dimension <3.2 cm; +1 for presence of a mid systolic notch or acceleration time <80 ms; –1 for lateral mitral E:e′>10; –1 for left atrial anterior-posterior dimension >4.2 cm. PVR increased stepwise with score (for –2, 0, and +2, μPVR were 2.5, 4.5, and 8.1 WU, respectively), whereas the inverse was true for pulmonary artery wedge pressure (corresponding μPAWP were 21.5, 16.5, and 10.4 mm Hg). Among subjects with complete data, the score had an area under the curve (AUC) of 0.921 for PH
PVD
. A score ≥0 had 100% sensitivity and 69.3% positive predictive value for PH
PVD
, with 62.3% specificity. No patients with a negative score had PH
PVD
. Patients with a negative score and acceleration time >100 ms had normal PVR (μPVR=1.8 WU, range=0.7–3.2 WU).

Conclusions—

We present a simple echocardiographic prediction rule that accurately defines PH hemodynamics, facilitates improved screening and focused clinical investigation for PH diagnosis and management.
Periprocedural Heparin Bridging in Patients Receiving Vitamin K Antagonists
Authors: Siegal Deborah , Yudin Jovana , Kaatz Scott , Douketis James D. , Lim Wendy , Spyropoulos Alex C.
Published: August 2012

Background—

Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established.

Methods and Results—

MEDLINE, EMBASE, and Cochrane databases (2001–2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (κ=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0–3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0–1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42–1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00–9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52–8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04–2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27–4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non–vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses.

Conclusions—

Vitamin K antagonist–treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging.
CO2 Snow Deposition in Antarctica to Curtail Anthropogenic Global Warming
Authors: Agee Ernest , Orton Andrea , Rogers John
Published: August 2012

A scientific plan is presented that proposes the construction of carbon dioxide (CO2) deposition plants in the Antarctic for removing CO2 gas from Earth’s atmosphere. The Antarctic continent offers the best environment on Earth for CO2 deposition at 1 bar of pressure and temperatures closest to that required for terrestrial air CO2 “snow” deposition—133 K. This plan consists of several components, including 1) air chemistry and CO2 snow deposition, 2) the deposition plant and a closed-loop liquid nitrogen refrigeration cycle, 3) the mass storage landfill, 4) power plant requirements, 5) prevention of dry ice sublimation, and 6) disposal (or use) of thermal waste. Calculations demonstrate that this project is worthy of consideration, whereby 446 deposition plants supported by sixteen 1200-MW wind farms can remove 1 billion tons (1012 kg) of carbon (1 GtC) annually (a reduction of 0.5 ppmv), which can be stored in an equivalent “landfill” volume of 2 km × 2 km × 160 m (insulated to prevent dry ice sublimation). The individual deposition plant, with a 100 m × 100 m × 100 m refrigeration chamber, would produce approximately 0.4 m of CO2 snow per day. The solid CO2 would be excavated into a 380 m × 380 m × 10 m insulated landfill, which would allow 1 yr of storage amounting to 2.24 × 10−3 GtC. Demonstrated success of a prototype system in the Antarctic would be followed by a complete installation of all 446 plants for CO2 snow deposition and storage (amounting to 1 billion tons annually), with wind farms positioned in favorable coastal regions with katabatic wind currents.
High-Resolution Vertical Profiles of X-Band Polarimetric Radar Observables during Snowfall in the Swiss Alps
Authors: Schneebeli Marc , Dawes Nicholas , Lehning Michael , Berne Alexis
Published: August 2012

An X-band polarimetric radar was deployed in the eastern Swiss Alps at an altitude of 2133 m. Radar measurements were complemented with several weather stations deployed in an altitude range from 1500 to 3100 m as well as with a fixed GPS ground station that was used to infer integrated water vapor estimates. Around 8000 vertical profiles of polarimetric radar observables above the melting layer collected during two months are analyzed. First, the behavior of the mean profiles of reflectivity at horizontal polarization Zh, differential reflectivity Zdr, copolar cross correlation ρhv, and specific differential phase shift Kdp are interpreted from a microphysical point of view. It is shown that the whole evolution of snowflakes, from pristine crystals at temperatures around −30°C to dendritic crystals around −15°C, to large aggregates around 0°C, is well captured by the polarimetric radar variables. In a second step, the profiles are analyzed as functions of high and low water vapor and snow accumulation conditions. It is found that the vertical profiles of polarimetric radar variables have distinct features in low versus high water vapor conditions. High water vapor conditions appear to favor the occurrence of crystal aggregates at high altitudes/low temperatures. It is shown with a hydrometeor identification scheme that graupel-like particles are found to be dominant right above the melting layer for snow events with high accumulation intensities. The present analyses show that measurements from X-band dual-polarization radar can be useful to characterize the dominant microphysical processes during precipitation in mountainous regions.
Influence of ENSO on the Diurnal Cycle of Rainfall over the Maritime Continent and Australia
Authors: Rauniyar Surendra P. , Walsh Kevin J. E.
Published: August 2012

This study examines the influence of ENSO on the diurnal cycle of rainfall during boreal winter for the period 1998–2010 over the Maritime Continent (MC) and Australia using Tropical Rainfall Measuring Mission (TRMM) and reanalysis data. The diurnal cycles are composited for the ENSO cold (La Niña) and warm (El Niño) phases. The k-means clustering technique is then applied to group the TRMM data into six clusters, each with a distinct diurnal cycle. Despite the alternating patterns of widespread large-scale subsidence and ascent associated with the Walker circulation, which dominates the climate over the MC during the opposing phases of ENSO, many of the islands of the MC show localized differences in rainfall anomalies that depend on the local geography and orography. While ocean regions mostly experience positive rainfall anomalies during La Niña, some local regions over the islands have more rainfall during El Niño. These local features are also associated with anomalies in the amplitude and characteristics of the diurnal cycle in these regions. These differences are also well depicted in large-scale dynamical fields derived from the interim ECMWF Re-Analysis (ERA-Interim).
Tracing Southwest Pacific Bottom Water Using Potential Vorticity and Helium-3
Authors: Downes Stephanie M. , Key Robert M. , Orsi Alejandro H. , Speer Kevin G. , Swift James H.
Published: August 2012

This study uses potential vorticity and other tracers to identify the pathways of the densest form of Circumpolar Deep Water in the South Pacific, termed “Southwest Pacific Bottom Water” (SPBW), along the 28.2 kg m−3 surface. This study focuses on the potential vorticity signals associated with three major dynamical processes occurring in the vicinity of the Pacific–Antarctic Ridge: 1) the strong flow of the Antarctic Circumpolar Current (ACC), 2) lateral eddy stirring, and 3) heat and stratification changes in bottom waters induced by hydrothermal vents. These processes result in southward and downstream advection of low potential vorticity along rising isopycnal surfaces. Using δ3He released from the hydrothermal vents, the influence of volcanic activity on the SPBW may be traced across the South Pacific along the path of the ACC to Drake Passage. SPBW also flows within the southern limb of the Ross Gyre, reaching the Antarctic Slope in places and contributes via entrainment to the formation of Antarctic Bottom Water. Finally, it is shown that the magnitude and location of the potential vorticity signals associated with SPBW have endured over at least the last two decades, and that they are unique to the South Pacific sector.
Internal Bores and Breaking Internal Tides on the Oregon Continental Slope
Authors: Martini Kim I. , Alford Matthew H. , Kunze Eric , Kelly Samuel M. , Nash Jonathan D.
Published: August 2012

Observations of breaking internal tides on the Oregon continental slope during a 40-day deployment of 5 moorings along 43°12′N are presented. Remotely generated internal tides shoal onto the slope, steepen, break, and form turbulent bores that propagate upslope independently of the internal tide. A high-resolution snapshot of a single bore is captured from lowered acoustic Doppler current profilers (LADCP)/CTD profiles in a 25-h time series at 1200 m. The bore is cold, salty, over 100 m tall, and has a turbulent head where instantaneous dissipation rates are enhanced (ε > 10−6 W kg−1) and sediment is resuspended. At the two deepest slope moorings (1452 and 1780 m), similar borelike phenomena are observed in near-bottom high-resolution temperature time series. Mean dissipation rates and diapycnal diffusivities increase by a factor of 2 when bores are present ( W kg−1 and m s−1) and observed internal tides are energetic enough to drive these enhanced dissipation rates. Globally, the authors estimate an average of 1.3 kW m−1 of internal tide energy flux is directed onto continental slopes. On the Oregon slope, internal tide fluxes are smaller, suggesting that it is a relatively weak internal tide sink. Mixing associated with the breaking of internal tides is therefore likely to be larger on other continental slopes.
Characterization of Riboflavin-modified Dentin Collagen Matrix
Authors: Fawzy A. , Nitisusanta L. , Iqbal K. , Daood U. , Beng L.T. , Neo J.
Published: August 2012

Crosslinking is considered a possible approach to increasing the mechanical and structural stability and biodegradation resistance of the dentin collagen matrix. The aim of this study was to investigate the mechanical and chemical variations and collagen degradation resistance associated with crosslinking of the dentin collagen matrix with UVA-activated riboflavin. Dentin collagen matrix specimens were treated with 0.1 and 1% riboflavin for 2 min and photo-activated with 7 mW/cm2 UVA (368 nm) for 2 min. The structural change of the dentin collagen network with collagenase exposure was investigated by AFM and SEM at different time-points. The variations in surface/bulk mechanical properties and biodegradation resistance were characterized by nano-indentation, conventional mechanical testing, and hydroxyproline liberation at different time-points. Chemical changes associated with riboflavin/collagen-matrix interaction were analyzed by micro-Raman spectroscopy. UVA-activated riboflavin increased the mechanical properties, mechanical stability, and biodegradation resistance of the dentin collagen matrix. Higher collagen-network structural resistance against collagenolytic challenges was found with crosslinking. micro-Raman spectroscopy showed a strong dependency, in both intensity and wave-number, of certain Raman bands (1242-1667 cm-1) with crosslinking indicating the collagen/riboflavin interactions. UVA-activated riboflavin (1%) more efficiently crosslinked the dentin collagen matrix within a relatively clinically acceptable time-frame compared with 0.1% riboflavin.
Effects of Using a Web-Based Individualized Education Program Decision-Making Tutorial
Authors: Shriner James G. , Carty Susan J. , Rose Chad A. , Shogren Karrie A. , Kim Myungjin , Trach John S.
Published: August 2012

This study explored the effects of a web-based decision support system ( Tutorial) for writing standards-based Individualized Education Programs (IEPs). A total of 35 teachers and 154 students participated across two academic years. Participants were assigned to one of three intervention groups based on level of Tutorial access: Full, Partial, or Comparison. Direct effects of the intervention on procedural and substantive elements of IEPs revealed that, although all groups had initial IEPs of similar quality, the Full Intervention group’s post- Tutorial IEPs had a significantly higher proportion of substantive items rated as adequate than did the IEPs of other groups. The intervention’s indirect effects were examined using student scores on the State Reading Assessment. The Full Intervention group demonstrated a higher rate of reading score gain than the other two groups during the academic year in which the IEP prepared with access to the Tutorial was implemented. Implications for educational practices and future research directions are discussed.
Negotiating Time and Space for Study: Student-parents and Familial Relationships
Authors: Brooks Rachel
Published: August 2012

Historically, university cultures have been described as masculine in orientation, and the ‘ideal learner’ as male, white, middle class and unencumbered by domestic responsibility. Nevertheless, more recent work has highlighted certain spaces within the higher education sector which, it is argued, are more welcoming of female students and those with family commitments. While there may now be more institutional spaces open to student-parents and others with caring responsibilities, we know little about whether similar change has been wrought in the domestic sphere. Drawing on interviews with 68 student-parents, this article explores the various strategies UK students with dependent children used to find time and space, within the home, to pursue their studies. By comparing these to the strategies used by student-parents at Danish universities, the article considers the extent to which differences in gender norms and state policy with respect to both higher education and childcare affect day-to-day familial practices.
Exploring Trends and Challenges in Sociological Research
Authors: McKie Linda , Ryan Louise
Published: August 2012

This is the first e-special issue for the journal Sociology and its chosen focus is the article ‘The coming crisis of empirical sociology’ by Savage and Burrows (2007). This article challenged sociologists with a variety of questions about the role, relevance and methodological opportunities for sociological research in the 21st century. On publication it stoked the already charged debates on a public sociology (Burawoy, 2004), the role of publicly funded research (ESRC, 2009) and relevance of sociological research in an age of burgeoning social media (Brewer and Hunter, 2006). This e-special provides a reprise of these debates and explores relevant papers in Sociology, as well as alerting readers to recurring themes and new directions on the topic of methods and social research.
Intersections of Gender, Race, and Class in Introductory Textbooks
Authors: Puentes Jennifer , Gougherty Matthew
Published: August 2012

We update Ferree and Hall’s (1996) examination of the stratification systems of gender, race, and class in introductory textbooks. Using a sample of textbooks from 2003 through 2010, we explore 24 introductory sociology textbooks to determine the relationship between categories of gender, race, and class and levels of analysis. Previous research found that textbooks primarily discuss gender at the micro level, race at the meso level, and class at the macro level. Replicating previous approaches by using index citations, we find evidence that gender is linked to socialization much more than race and class, and there is evidence that class is still more likely to be discussed at a macro level. Our content analysis findings show a similar pattern, but also some evidence for the increased inclusion of theories and examples that examine gender, race, and class at multiple levels of analysis. Implications of these findings are discussed.
The Role of L‐Arginine and Inducible Nitric Oxide Synthase in Intestinal Permeability and Bacterial Translocation
Authors: Quirino Iara Eliza Pacífico , Cardoso Valbert Nascimento , Santos Rosana das Graças Carvalho dos , Evangelista Warlley Pinheiro , Arantes Rosa Maria Esteves , Fiúza Jacqueline Araújo , Glória Maria Beatriz Abreu , Alvarez‐Leite Jacqueline Isaura , Batista Marina Andrade , Correia Maria Isabel Toulson Davisson
Published: August 2012

Background: Arginine has been shown to have several immunological and trophic properties in stressful diseases. Its metabolites, nitric oxide (NO) and polyamines, are related to arginine's effects. Thus, the aim of this study was to determine the effects of the NO donor L‐arginine and the role of inducible NO synthase (iNOS) on intestinal permeability and bacterial translocation in a model of intestinal obstruction (IO) induced by a simple knot in the terminal ileum. Material and Methods: Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham–/– (standard chow), IO and IO–/– (standard chow +IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chows, IO was induced and intestinal permeability and bacterial translocation were evaluated. The small intestine and its contents were harvested for histopathological and morphometric analysis and the determination of polyamine concentration. Results: Pretreatment with arginine maintained intestinal permeability (P > .05; Arg and Arg–/– groups vs Sham and Sham–/– groups), increased polyamine concentration in intestinal content (P < .05; Arg vs IO group), and decreased bacterial translocation in WT animals (Arg group vs IO and IO–/– groups). Absence of iNOS also presented a protective effect on permeability but not on bacterial translocation. Conclusion: Arginine supplementation and synthesis of NO by iNOS are important factors in decreasing bacterial translocation. However, when intestinal permeability was considered, NO had a detrimental role.
Transitional NPH Insulin Therapy for Critically Ill Patients Receiving Continuous Enteral Nutrition and Intravenous Regular Human Insulin
Authors: Dickerson Roland N. , Wilson Vera C. , Maish George O. , Croce Martin A. , Minard Gayle , Brown Rex O.
Published: August 2012

Background: The intent of this study was to evaluate the efficacy and safety of transitioning from a continuous intravenous (IV) regular human insulin (RHI) or intermittent IV RHI therapy to subcutaneous neutral protamine Hagedorn (NPH) insulin with intermittent corrective IV RHI for critically ill patients receiving continuous enteral nutrition (EN). Methods: Data were obtained from critically ill trauma patients receiving continuous EN during transitional NPH insulin therapy. Target blood glucose concentration (BG) range was 70–149 mg/dL. BG was determined every 1–4 hours. Results: Thirty‐two patients were transitioned from a continuous IV RHI infusion (CIT) to NPH with intermittent corrective IV RHI therapy. Thirty‐four patients had NPH added to their preexisting supplemental intermittent IV RHI therapy (SIT). BG concentrations were maintained in the target range for 18 ± 3 and 15 ± 4 h/d for the CIT and SIT groups, respectively (P < .05). Thirty‐eight percent of patients experienced a BG <60 mg/dL, and 9% had a BG <40 mg/dL. Hypoglycemia was more prevalent for those who were older (P < .01) or exhibited greater daily BG variability (P < .01) or worse HgbA1C (p < 0.05). Conclusion: Transitional NPH therapy with intermittent corrective IV RHI was effective for achieving BG concentrations within 70–149 mg/dL for the majority of the day. NPH therapy should be implemented with caution for those who are older, have erratic daily BG control, or have poor preadmission glycemic control.
Objectivity and its discontents
Authors: Anderson Warwick
Published: August 2012

In my 2008 book, The Collectors of Lost Souls, I told the story of the medical investigation of kuru, a fatal brain disease afflicting the Fore people of New Guinea during the middle of the 20th century. The story involved sorcery accusations, cannibalism, first contact, colonial incursions, scientific rivalry, alleged sexual molestation, and two Nobel Prizes in Physiology or Medicine. There can be little doubt that kuru, because of its peculiarities, has proven exceptionally ‘good to think with’—in infectious diseases research, medical anthropology and the history of science. Here, I attempt a cultural history of valuation in kuru research, hoping thus to make a tentative contribution to a theory of value in modern science. It is important to distinguish this project from functionalist and normative analyses predicated on conceptions of social structure and solidarity. Instead, I want to look at the inter-subjective mobilization and modulation of desire in scientific work, thus focusing on multiple agency, more than structure, in the making or perception of value. Like John Dewey, and his teacher Georg Simmel, I am most interested in how experiences of self-formation generate or reveal value commitments; that is, I am interested in how interaction, or opening ourselves to others, can form and make visible our values and valuables. In this spirit, I want to attend to the commitments to subjects and objects that emerge through cultural contact and exchange in scientific research.
Top Nurse-Management Staffing Collapse and Care Quality in Nursing Homes
Authors: Hunt Selina R. , Corazzini Kirsten , Anderson Ruth A.
Published: August 2012

Director of nursing turnover is linked to staff turnover and poor quality of care in nursing homes; however the mechanisms of these relationships are unknown. Using a complexity science framework, we examined how nurse management turnover impacts system capacity to produce high quality care. This study is a longitudinal case analysis of a nursing home ( n = 97 staff) with 400% director of nursing turnover during the study time period. Data included 100 interviews, observations and documents collected over 9 months and were analyzed using immersion and content analysis. Turnover events at all staff levels were nonlinear, socially mediated and contributed to dramatic care deficits. Federal mandated, quality assurance mechanisms failed to ensure resident safety. High multilevel turnover should be elevated to a sentinel event for regulators. Suggestions to magnify positive emergence in extreme conditions and to improve quality are provided.
Genotoxic evaluation of two oral antidiabetic agents in the Drosophila wing spot test
Authors: Gürbüzel Mehmet , Çapoğlu İlyas , Kızılet Halit , Halıcı Zekai , Özçiçek Fatih , Demirtaş Levent
Published: August 2012

In this study, two sulfonylureas—glimepiride and glipizide—commonly used in type 2 diabetes mellitus were investigated for genotoxicity in the Drosophila wing spot test. For this purpose, three-day-old transheterozygous larvae were treated with three mutagenic compounds, and the results obtained were compared with the control group. Mutational or recombinogenic changes were recorded in two recessive genes— multiple wing hairs ( mwh) and flare ( flr3). Two recessive markers were located on the left arm of chromosome 3, mwh in map position 0.3, and flare-3 ( flr3) at 38.8, while the centromere was located in position 47.7. Wing spot tests are targeted on the loss of heterozygosity, which may be grounded in different genetic mechanisms such as mutation, mitotic recombination, deletion, half-translocation, chromosome loss, or nondisjunction. Genetic changes formatting in somatic cells of the imaginal discs cause nascence different mutant cloning in different body parts of adult flies. Our in vivo experiments demonstrated that glimepiride and glipizide show the genotoxicity, which is especially dependent on homologous somatic recombination.
Toxicological effect of N, N, N′, N′-tetramethylethylene on rat brain acetylcholinesterase
Authors: Ahmed Mushtaq , Latif Nadia , Khan Rahmat Ali , Ahmad Akhlaq , Schetinger Maria RC , Rocha João BT
Published: August 2012

N, N, N′, N′-tetramethylethylenediamine (TEMED) is extensively used for initiating polymerization of acrylamide and bisacrylamide gel for electrophoresis and for inorganic complex structure formation. The present study evaluates the toxicological effect of TEMED on structures of rat brain acetylcholinesterase (AChE) activity . In vitro study showed that the Ki values for striatum, cortex, cerebellum and hypothalamus were found to be 1.24, 1.4, 1.45 and 1.47 mM. Kinetics studies indicated that TEMED caused mixed type of inhibition that is a combination of competitive and noncompetitive inhibition in striatum, cortex, hypothalamus and cerebellum. The result showed that km increased and Vmax decreased with increase in TEMED concentration. The IC50 values calculated for striatum, cortex, cerebellum and hypothalamus were found to be as 0.92, 0.92, 1.44 and 1.42 mM. The present study indicates that TEMED is a toxicant for brain via inhibition of AChE. Therefore, proper precaution should be made during its handling.
Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats
Authors: El-Shinnawy Nashwa A , Abd-Elmageid Samira A , Alshailabi Eda MA
Published: August 2012

The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity  were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.
Case of Infantile Onset Spinocerebellar Ataxia Type 5
Authors: Jacob Francois-Dominique , Ho Eugenia S. , Martinez-Ojeda Mayra , Darras Basil T. , Khwaja Omar S.
Published: August 2012

Dominant spinocerebellar ataxias are a rare clinically and genetically heterogeneous group of neurodegenerative disorders. They are characterized by progressive cerebellar ataxia resulting in unsteady gait, clumsiness, dysarthria, and swallowing difficulty. The onset of symptoms is usually in the third or fourth decade of life; however, more subtle clinical manifestations can start in early childhood. Spinocerebellar ataxia type 5, a dominant spinocerebellar ataxia associated with mutations involving β-III spectrin ( SPTBN2), has been described in 3 families. It typically consists of a slowly progressive spinocerebellar ataxia with onset in the third decade. The authors present the first case of infantile-onset spinocerebellar ataxia associated with a novel SPTBN2 mutation (transition C>T at nucleotide position 1438), the proband having a much more severe phenotype with global developmental delay, hypotonia, tremor, nystagmus, and facial myokymia.
Acute Disseminated Encephalomyelitis
Authors: Alper Gulay
Published: August 2012

Acute disseminated encephalomyelitis is an immune-mediated inflammatory and demyelinating disorder of the central nervous system, commonly preceded by an infection. It principally involves the white matter tracts of the cerebral hemispheres, brainstem, optic nerves, and spinal cord. Acute disseminated encephalomyelitis mainly affects children. Clinically, patients present with multifocal neurologic abnormalities reflecting the widespread involvement in central nervous system. Cerebrospinal fluid may be normal or may show a mild pleocytosis with or without elevated protein levels. Magnetic resonance image (MRI) shows multiple demyelinating lesions. The diagnosis of acute disseminated encephalomyelitis requires both multifocal involvement and encephalopathy by consensus criteria. Acute disseminated encephalomyelitis typically has a monophasic course with a favorable prognosis. Multiphasic forms have been reported, resulting in diagnostic difficulties in distinguishing these cases from multiple sclerosis. In addition, many inflammatory disorders may have a similar presentation with frequent occurrence of encephalopathy and should be considered in the differential diagnosis of acute disseminated encephalomyelitis.
Properties and osteoblast cytocompatibility of self-curing acrylic cements modified by glass fillers
Authors: Lopes PP , Garcia MP , Fernandes MH , Fernandes MHV
Published: August 2012

Materials filled with a silicate glass (MSi) and a borate glass (MB) were developed and compared in terms of their in vitro behavior. The effect of filler composition and concentration (0, 30, 40 and 50 wt%) on the curing parameters, residual monomer, water uptake, weight loss, bioactivity, mechanical properties (bending and compression) and osteoblast cytocompatibility was evaluated. The addition of bioactive glass filler significantly improved the cements curing parameters and the mechanical properties. The most relevant results were obtained for the lower filler concentration (30 wt%) a maximum flexural strength of 40.4 MPa for MB3 and a maximum compressive strength of 95.7 MPa for MSi3. In vitro bioactivity in acellular media was enhanced by the higher glass contents in the cements. Regarding the biological assessment, the incorporation of the silicate glass significantly improved osteoblast cytocompatibility, whereas the presence of the borate glass resulted in a poor cell response. Nevertheless it was shown that the surviving cells on the MB surface were in a more differentiated stage compared to those growing over non-filled poly(methyl methacrylate). Results suggest that the developed formulations offer a high range of properties that might be interesting for their use as self-curing cements.