bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased ovarian function is associated with obesity in very long-term female survivors of childhood cancer
Authors: van Dorp W , Blijdorp K , Laven J S E , Pieters R , Visser J A , van der Lely A J , Neggers S J C M M , van den Heuvel-Eibrink M M
Published: April 2013

Objective

Obesity and gonadal dysfunction are known major side effects of treatment in adult childhood cancer survivors (CCS). In the general population, obesity has a negative influence on female fertility. We aimed to evaluate whether obesity and serum insulin are associated with decreased ovarian reserve markers in CCS.

Design

Retrospective single-center cohort study.

Methods

Data of 191 female survivors of childhood cancer were analyzed. Median follow-up time was 18.8 (2.3–48.8) years. Outcome measures were serum anti-Müllerian hormone (AMH) and total follicle count (FC). Potential risk factors were: BMI; body composition measures, determined by dual-energy X-ray absorptiometry (total fat percentage, lean body mass, and visceral fat percentage); and fasting insulin.

Results

Lower serum AMH was found in obese subjects (β(%) −49,P=0.007) and in subjects with fasting insulin in the highest tertile (β(%) −43,P=0.039). Total fat percentage tends to be associated with serum AMH (β(%) −2.1,P=0.06). Survivors in the highest tertile of insulin had significantly lower FC than survivors in the lowest tertile (β−6.3,P=0.013). BMI and other measures of body composition were not associated with FC. Correlation between serum AMH and antral follicle count (AFC) wasρ=0.32 (P=0.08).

Conclusions

Obesity and insulin resistance are associated with gonadal damage, as reflected by decreased AMH and reduced FC in adult survivors of childhood cancer. In contrast to its highly predictive value for AFC in the healthy female population, serum AMH does not seem to correlate as well with AFC in CCS.
The effects of alumina-leached coal fly ash residue on magnesium oxychloride cement
Authors: Wu Chengyou , Zhang Huifang , Yu Hongfa
Published: April 2013

Effects of alumina-leached coal fly ash residue (ACFAR) on magnesium oxychloride (MOC) cement are comprehensively investigated. The results show that the addition of ACFAR delayed the setting time of MOC paste. The compressive strength, the flexural strength and the water resistance of MOC are improved by the incorporation of ACFAR. Furthermore, the improvement effects of ACFAR are compared with those of raw coal fly ash (RFA) on MOC cement. Scanning electron microscopy analysis of MOC cement reveals that ACFAR decreases the interspaces in MOC cement and facilitates the radial growth of 5Mg(OH)2·MgCl2·8H2O. X-ray diffraction analysis of MOC cement with ACFAR indicates that the addition of ACFAR promotes the production of magnesium silicate, which can improve the compactness of 5Mg(OH)2·MgCl2·8H2O and the water resistance of MOC cement.
Rock compressibility at the Wairakei–Tauhara geothermal field, New Zealand
Authors: Pender Michael , Ramsay Graham , Glynn-Morris Trystan , Lynne Bridget , Bromley Chris
Published: April 2013

Geothermal fluid has been extracted from the Wairakei field in New Zealand since the mid-1950s for electricity generation. This has induced regional subsidence of more than 1 m; in addition, there are a few localised bowls with much greater subsidence. A comprehensive geotechnical investigation with recovery of undisturbed samples from depths of up to 774 m was undertaken with testing of samples from within and outside subsidence bowls to determine material properties, with the aim of improved understanding of subsidence within the Wairakei–Tauhara geothermal system. Results from more than 130 K0 triaxial compression tests on core samples are discussed. Given the volcanic origins of most of the material present, a wide variation in the measured constrained modulus values is not surprising. Scanning electron microscope images reveal differences between the texture of the soft materials and the very stiff materials; these correlate with the constrained modulus values. The applicability of the Terzaghi effective stress equation is considered in relation to the measured property values; the conventional equation remains valid even for the least compressible materials tested.
Influence of Postemergence Herbicides on Weed Management in Spring‐Sown Linseed
Authors: Karimmojeni Hassan , Pirbaloti Ahmad G. , Kudsk Per , Kanani Vahid , Ghafori Abbas
Published: April 2013

Linseed (Linum usitatissimum L.) is a very poor competitor with weeds, and to obtain acceptable linseed yields, weeds should be effectively controlled. Very little information is available on the tolerance of linseed to herbicide applications. In this study, the effects of nine herbicide treatments on the control of broadleaf weeds and yield response in spring‐sown linseed were evaluated. The dominant weed species were garden rocket (Eruca sativa Mill.) and field bindweed (Convolvulus arvensis L.). A tank mixture of bromoxynil (337.5 g a.i. ha–1.) plus a nonionic surfactant was more effective than bromoxynil applied alone at 450 g a.i. ha–1 and led to greater yield increases. In contrast, addition of a nonionic surfactant to bentazon did not overcome a reduction in the bentazon dose from 960 to 720 g a.i. ha–1, and the linseed yield was the same or lower than that of bentazon alone. Bromoxynil plus MCPA provided effective weed control but caused crop damage and resulted in lower yields than some of the other herbicides. Similarly, dichlorprop‐P plus mecoprop‐P plus MCPA caused severe crop phytotoxicity and reduced yield. The study confirmed that weeds can severely diminish linseed productivity and that many broadleaf weed herbicides can severely damage the linseed crop. We conclude that bentazon (1440 g a.i. ha–1), bromoxynil (337.5 g ha–1 a.i.) plus a nonionic surfactant, and 2, 4‐D plus MCPA are good options for chemical control of broadleaf weeds in linseed because they protected yield by providing satisfactory levels of weed control with acceptable levels of crop phytotoxicity.
Biochemical Processes Controlling Soil Nitrogen Mineralization under Waterlogged Conditions
Authors: Haddad S. A. , Tabatabai M. A. , Loynachan T. E.
Published: April 2013

Changes in precipitation patterns in recent years have resulted in flooding or ponding of many farmlands in the North Central region of the United States. In this work, 11 field‐moist surface soils (0–15 cm) and their air‐dried counterparts were incubated at 30°C under waterlogged conditions for times ranging from 3 to 15 d, and the amounts of NH4–N released were determined. Results showed that, presumably because of slaking effects, the rates of NH4–N release were greater in air‐dried than in field‐moist soils. The mineralization rates of the field‐moist soils were significantly correlated with organic C (r = 0.59, P < 0.05), organic N (r = 0.69, P < 0.05), and microbial biomass C (r = 0.62, P < 0.05) and N (r = 0.63, P < 0.05). The corresponding r values for the air‐dried soils were 0.76 (P < 0.01), 0.87 (P < 0.01), 0.84 (P < 0.01), and 0.85 (P < 0.001), respectively. Estimation of the amounts of N mineralized per hectare of field‐moist soils in 1 d ranged from 2.2 to 4.9 kg (average = 3.3). Those values for air‐dried soils ranged from 5.2 to 26.2 kg (average = 15.5). The rates of hydrolysis of six enzyme substrates studied were significantly correlated with the rates of NH4–N release in the field‐moist soils. The relationships were amidase (r = 0.82, P < 0.01), arginase (r = 0.90, P < 0.001), asparaginase (r = 0.86, P < 0.001), glutaminase (r = 0.88, P < 0.001), β‐glucosidase (r = 0.83, P < 0.01), and β‐glucosaminidase (r = 0.84, P < 0.01). Temperature coefficient (Q10) values ranged from 1.2 to 1.4 (average = 1.3) for the field‐moist soils and from 1.0 to 1.3 (average = 1.1) for their air‐dried counterparts. This study showed that microbial biomass, a number of hydrolases, and slaking seem to play a significant role in hydrolysis of N in temporarily flooded soils.
Improving Estimates of Soil Salinity from Saturation Paste Extracts in Calcareous Soils
Authors: Amakor Xystus N. , Jacobson Astrid R. , Cardon Grant E.
Published: April 2013

In the arid and semiarid western United States, accurate measurement of soil salinity by electrolytic conductivity can be a challenge due to the formation of ion pairs in the high ionic strength soil solutions that affect estimates of the total quantity of ions in solution. Continued underestimation of total dissolved solids (TDS) threatens the long‐term sustainable management of irrigated agricultural lands in regions faced with a threat of soil salinization. This study aims to improve estimates of soil salinity in calcareous soils. We hypothesized that saturation paste extracts can be diluted to a point where ion pair formation is minimized, so that the electrical conductivity (EC) of the saturation paste extract (ECe) can be used to more accurately predict soil salinity. Results of an analytical conceptual model using salt solutions and ion speciation modeling of these solutions suggest that 0.03 to 0.05 dS m–1 is the optimal EC range beyond which dilutions produce negligible decreases in EC and where approximately 99% of the ion species occur as free ions. Diluting soil saturation paste extracts to conductivities <0.05 dS m–1 (e.g., in our samples by a factor of approximately 1000), minimized ion pairing as supported by analysis of ions in solution, solution speciation with visual Minteq, and comparisons of calculated TDS (in mmol L–1). To therefore improve the estimates of salinity in calcareous soils, we recommend diluting the saturated paste extracts to EC < 0.05 dS m–1, computing TDS from the diluted EC values, and then multiplying the TDS by the dilution factor.
Factors Regulating Net Methane Flux by Soils in Urban Forests And Grasslands
Authors: Costa Karina H. , Groffman Peter M.
Published: April 2013

Long‐term studies in the Baltimore, MD USA metropolitan area have found higher CH4 uptake by soils in rural versus urban forests and no net uptake in urban lawns. Here, we investigated three factors that could be causing this inhibition; reduced diffusion of CH4 into soils, production of CH4 in anaerobic microsites and N additions from fertilizer or atmospheric deposition. Patterns of consumption in homogenized soils in the laboratory were comparable with previous field results, eliminating diffusion as a possible inhibiting mechanism. No CH4 was produced in anaerobic incubations, signifying that microsite production was not important. Nitrogen additions had no effect on consumption of ambient CH4, suggesting that N inputs do not immediately inhibit uptake. However, there were strong negative relationships between CH4 uptake and nitrification, suggesting that long‐term differences in N cycling associated with urban land use change may have led to a reduction in the microbial populations responsible for methane uptake.
Theoretical Comparison of Advanced Methods for Calculating Nitrous Oxide Fluxes using Non‐steady State Chambers
Authors: Venterea Rodney T.
Published: April 2013

Non‐steady state (NSS) chambers provide much of the data used in bottom‐up assessments of global nitrous oxide (N2O) emissions. Due to inherent limitations in NSS chambers and flux calculation (FC) methods, it is likely that these assessments are negatively biased. Potentially more accurate FC schemes have been developed recently. However, there is little consensus regarding optimum FC methods and they are often selected without critical evaluation of their theoretical basis. This study used diffusion modeling to assess the accuracy of several advanced and conventional FC methods under conditions that both adhered to and violated theoretical assumptions on which the methods are based. Two methods (non‐steady‐state diffusive flux estimator [NDFE] and chamber bias correction [CBC]) having the same theoretical basis but differing computational approaches displayed contrasting behavior. The NDFE tended to overestimate the actual pre‐deployment flux (f0) to an increasing degree as assumptions were increasingly violated. In contrast, CBC was most accurate over the broadest range of conditions and relatively insensitive to assumption violation, except when unaccounted‐for processes increased above certain levels. Modified R‐based Hutchinson and Mosier method (HMR) underestimated f0 under all conditions but became more accurate relative to NDFE and CBC as lateral gas diffusion and soil biological N2O uptake increased. This analysis offers new insight into the behavior of FC schemes under varying conditions and provides additional evidence that the most commonly used schemes tend to substantially underestimate f0. Improved understanding of the theoretical basis and limitations of FC schemes should promote more prudent use of chambers, development of improved methods, and more accurate N2O flux estimates at the site‐ and global‐scale.
Quantitative Immunohistochemistry of Desmosomal Proteins (Plakoglobin, Desmoplakin and Plakophilin), Connexin-43, and N-cadherin in Arrhythmogenic Cardiomyopathy: An Autopsy Study
Authors: Tavora Fabio , Zhang Mingchang , Cresswell Nathaniel , Li Ling , Fowler David , Franco Marcello , Burke Allen
Published: April 2013

Background:

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder related to mutations in desmosomal proteins. The current study tests the hypothesis that immunohistochemical staining for desmosomal proteins is of diagnostic utility by studying autopsy-confirmed cases of ARVC.

Methods and Results:

We studied 23 hearts from patients dying suddenly with ARVC. Control subject tissues were 21 hearts from people dying from non-cardiac causes (n=15), dilated cardiomyopathy (n=3) and coronary artery disease (n=3).

Areas free of fibrofatty change or scarring were assessed on 50 sections from ARVC (24 left ventricle, 26 right ventricle) and 28 sections from controls. Immunohistochemical stains against plakoglobin, plakophilin, desmoplakin, connexin-43, and N-cadherin were applied and area expression analyzed by computerized morphometry. Desmin was stained as a control for fixation and similarly analyzed.

The mean area of desmin expression was similar in controls and ARVC (86% vs. 85%, p=0.6). Plakoglobin expression was 4.9% ± 0.3% in controls, vs. 4.6% ± 0.3% in ARVC (p=0.3). Plakophilin staining was 4.8% ± 0.3% in controls vs. 4.4% ± 03% in ARVC (p=0.3). Desmoplakin staining was 3.4% in controls vs. 3.2 ± 0.2% in ARVC (p=0.6). There were no significant differences when staining was compared between right and left ventricles (all p > 0.1).

For non-desmosomal proteins, the mean area of connexin-43 staining showed no significant difference by presence of disease.

Conclusions:

The small and insignificant decrease in junction protein expression in ARVC suggests that immunohistochemistry is not a useful tool for the diagnosis.
Identification of a Loss-of-Function Mutation in Ube2l6 Associated With Obesity Resistance
Authors: Marcelin Genevieve , Liu Shun-Mei , Schwartz Gary J. , Chua Streamson C.
Published: April 2013

We previously mapped a locus on BALB/c chromosome 2 associated with protection from leptin-deficiency–induced obesity. Here, we generated the corresponding congenic mouse strain by introgression of a segment of C57BL/6J chromosome 2 to the BALB/c background to confirm the genotype–phenotype associations. We found that the BALB/c alleles decreased fat mass expansion by limiting adipocyte hyperplasia and adipocyte hypertrophy. This was concomitant to an increase in adipocyte triglyceride lipase (ATGL)-mediated triglyceride breakdown and prolongation of ATGL half-life in adipose tissue. In addition, BALB/c alleles on chromosome 2 exerted a cell-autonomous role in restraining the adipogenic potential of preadipocytes. Within a 9.8-Mb critical interval, we identified a nonsynonymous coding single nucleotide polymorphism in the gene coding for the ubiquitin-conjugating enzyme E2L6 (Ube2l6, also known as Ubch8) and showed that the BALB/c allele of Ube2l6 is a hypomorph leading to the lack of UBE2L6 protein expression. Ube2l6 knockdown in 3T3-L1 adipocytes repressed adipogenesis. Thus, altered adipogenic potential caused by Ube2l6 knockdown is likely critically involved in BALB/c obesity resistance by inhibiting adipogenesis and reducing adipocyte numbers. Overall, we have identified a loss-of-function mutation in Ube2l6 that contributes to the chromosome 2 obesity quantitative trait locus.
Mammalian Target of Rapamycin Regulates Nox4-Mediated Podocyte Depletion in Diabetic Renal Injury
Authors: Eid Assaad A. , Ford Bridget M. , Bhandary Basant , de Cassia Cavaglieri Rita , Block Karen , Barnes Jeffrey L. , Gorin Yves , Choudhury Goutam Ghosh , Abboud Hanna E.
Published: April 2013

Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Pharmacological doses of the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduce albuminuria in diabetes. We explored the hypothesis that mTOR mediates podocyte injury in diabetes. High glucose (HG) induces apoptosis of podocytes, inhibits AMP-activated protein kinase (AMPK) activation, inactivates tuberin, and activates mTOR. HG also increases the levels of Nox4 and Nox1 and NADPH oxidase activity. Inhibition of mTOR by low-dose rapamycin decreases HG-induced Nox4 and Nox1, NADPH oxidase activity, and podocyte apoptosis. Inhibition of mTOR had no effect on AMPK or tuberin phosphorylation, indicating that mTOR is downstream of these signaling molecules. In isolated glomeruli of OVE26 mice, there is a similar decrease in the activation of AMPK and tuberin and activation of mTOR with increase in Nox4 and NADPH oxidase activity. Inhibition of mTOR by a small dose of rapamycin reduces podocyte apoptosis and attenuates glomerular injury and albuminuria. Our data provide evidence for a novel function of mTOR in Nox4-derived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. Thus, mTOR and/or NADPH oxidase inhibition may represent a therapeutic modality of diabetic kidney disease.
β-Cell Lipotoxicity in Response to Free Fatty Acid Elevation in Prepubertal Youth
Authors: Michaliszyn Sara F. , Bonadonna Riccardo C. , Sjaarda Lindsey A. , Lee SoJung , Farchoukh Lama , Arslanian Silva A.
Published: April 2013

Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion, which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide–modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of first- and second-phase insulin secretion showed a significant condition × race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in AA and C youth, with a significantly greater decrease in Cs compared with AAs. In conclusion, AA and C prepubertal youth both demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, that AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion, consistent with our theory.
Wear debris from hip prostheses characterized by electron imaging
Authors: Topolovec Matevž , Milošev Ingrid , Cör Andrej , Bloebaum Roy
Published: April 2013

The characterization of wear particles is of great importance in understanding the mechanisms of osteolysis. In this unique study, thirty-one tissue samples were retrieved at revision surgeries of hip implants and divided into four groups according to the composition of metal prosthetic components. Tissue samples were first analyzed histologically and then by scanning electron microscopy (SEM) combined with back-scattered electron imaging and energy dispersive X-ray spectroscopy. Therefore, particles were studied directly in situ in tissue sections, without the requirement for particle isolation. The composition of metal wear particles detected in the tissue sections corresponded to the composition of the implant components. A considerable number of large metal particles were actually clusters of submicron particles. The clustering of submicron particles was observed primarily with CoCrMo (cobalt-chromiummolybdenum) and, to a lesser extent, for stainless steel particles. SEM secondary and back-scattered electron imaging was an appropriate and selective method for recognizing the composition of metal particles in the in situ tissue sections, without destroying their spatial relationship within the histology. This method can be used as a screening tool for composition of metal and ceramic particles in tissue sections, or as an additional method for particle identification.
Building the Research Capacity of Clinical Physical Therapists Using a Participatory Action Research Approach
Authors: Janssen Jessie , Hale Leigh , Mirfin-Veitch Brigit , Harland Tony
Published: April 2013

Background

This 2-year study explored the experiences of clinical physical therapists who used a participatory action research (PAR) approach to learn about the practice of clinical research.

Objectives

The aim of this study was to explore the experiences of physical therapists who were conducting clinical research, facilitated by a PAR approach.

Design

A mixed-methods research design was used.

Methods

Physical therapists completed questionnaires, were interviewed, and participated in focus groups prior to and after the 1-year intervention and 1 year later. The research facilitator took field notes. Questionnaire data were analyzed descriptively, and themes were developed from the qualitative data. Twenty-five therapists took part in 4 self-selected groups.

Results

Three groups actively participated in the PAR research projects (n=14). The remaining 11 therapists decided not to be involved in clinical research projects but took part in the study as participants. After 1 year, one group completed the data collection phase of their research project, and a second group completed their ethics application. The third group ceased their research project but hosted a journal club session. At completion of the study, the experiences of the physical therapists were positive, and their confidence in conducting research and orientation toward research had increased. The perceptions of physical therapists toward research, relationships among individuals, and how the clinical projects were structured influenced the success of the projects.

Limitations

Only physical therapists of one hospital and no other health care practitioners were included in this study.

Conclusions

Fourteen physical therapists divided among 3 PAR groups were overall positive about their experiences when they conducted a research project together. This finding shows that a PAR approach can be used as a novel tool to stimulate research participation in clinics.
"Barbaric Laws, Barbaric Bonds": Arnold Wesker's The Merchant
Authors: Alter Iska
Published: April 2013

If The Merchant of Venice is not the most problematic of Shakespeare's plays, it certainly has become one of the most provocative, not to say provoking, for the contemporary sensibility, schooled by history to the horrific outcome of anti-Jewish prejudice in the twentieth century. A tentative hint suggesting the possibility of a production is often enough to generate a cause celebre, prompting attacks on the playwright, cries of outrage against the theatre, and the inevitable demands for censorship among those who view the playas an antisemitic desecration. Once a production has been mounted, unless Shylock has been interpreted as an appropriately heroic if frequently sentimentalized figure, attacks often recur.
Throwing Theory at Ireland? The Field Day Theatre Company and Postcolonial Theatre Criticism
Authors: Richards Shuan
Published: April 2013

Writing in 2000, the literary critic Richard Kirkland noted, "[I]t is clear that most considerations of theory and Ireland are now roughly reducible to postcolonial theory — a transition which would have been unthinkable ten years ago". A range of recent work demonstrates the extent to which critics of Irish drama have embraced "postcolonial" analysis. I However, in drama criticism specifically, and literary criticism more widely, a considered analysis of the adequacy of the term is frequently as absent as its application is ubiquitous. This essay is an examination of the development of postcolonial readings of Irish drama through the lens of the Field Day Theatre Company, tracing its progression as a mode of analysis and, crucially, its perceived and actual limitations. In particular it looks to extend the critique of the company beyond the exhausted framework of Anglo-Irish relations and locate it within the dynamic definition of the postcolonial developed by critics such as Robert Young, for whom the "economic dominance" of one part of the world over another is the fundamental "assumption of postcolonial studies". His observation that "postcolonial theory's intellectual commitment will always be to seek to develop new forms of engaged theoretical work" informs the present analysis, in which Translations, described by Seamus Deane as Field Day's "central text" is read in a creative transcendence of the condemnations of its critics. In Young's terms, a progressive postcolonial analysis must ensure that "[i]nterest in oppression of the past will always be guided by the relation of that history to the present", and it is the precise nature of the global "present" to which the argument is particularly directed.
Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma
Authors: Sloan Andrew E. , Ahluwalia Manmeet S. , Valerio-Pascua Jose , Manjila Sunil , Torchia Mark G. , Jones Stephen E. , Sunshine Jeffrey L. , Phillips Michael , Griswold Mark A. , Clampitt Mark , Brewer Cathy , Jochum Jennifer , McGraw Mary V. , Diorio Dawn , Ditz Gail , Barnett Gene H.
Published: April 2013

Object

Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose–escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).

Methods

Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, side-firing laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation.

Results

Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals–Case Medical Center). Their average age was 55 years (range 34–69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70–90). The mean tumor volume was 6.8 ± 5 cm3 (range 2.6–19 cm3), the percentage of tumor treated was 78% ± 12% (range 57%–90%), and the conformality index was 1.21 ± 0.33 (range 1.00–2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62–767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose.

Conclusions

NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. Clinical trial registration no.: NCT00747253 (ClinicalTrials.gov).
Biomechanical evaluation of 2 insertion points for ventral screw fixation of C-2 dens fractures
Authors: Oberkircher Ludwig , Bliemel Christopher , Flossdorf Felix , Schwarting Tim , Ruchholtz Steffen , Krüger Antonio
Published: April 2013

Object

For many Type II fractures of the dens (Anderson and D'Alonzo classification), a double anterior screw fixation is performed. If screw disruption occurs, the location is most often at the anterior caudal endplate and body of the axis and not directly at the fracture line. The authors' objective was to determine the differences in primary mechanical stability at 2 insertion points used in ventral screw fixation of Type II fractures of the C-2 dens.

Methods

Screw fixation was performed on 16 formalin-fixed human C-2 dens specimens. The specimens were divided into 2 groups. For Group 1, the screws were inserted directly at the anterior lower endplates; for Group 2, the screws were inserted 2 mm dorsal to the anterior wall of the vertebral body. After a Type II odontoid fracture was created with an oscillating saw, screw fixation was performed using two 3.5-mm partially threaded lag screws with washers. Subsequently, each vertebral body was continuously loaded. The criterion for breakage was reversal of the force vector.

Results

In Group 1, screw disruption occurred at the point of entry; the mean load failure was 290.5 ± 106 N. In Group 2, no screw disruption occurred; the mean load failure was 574.2 ± 170.5 N. These results were significant (p < 0.05).

Conclusions

For double screw fixation of Type II fractures of the dens (Anderson and D'Alonzo classification), placement of the screws as far dorsal to the anterior lower endplate as possible seems to favorably affect primary stability. In actual clinical practice, care should be taken to not damage the anterior wall of the vertebral body of the axis during screw insertion.
Speaking a ‘Stammering Speech’: Tadeusz Kantor as ‘Poor’ Messenger
Authors: Leach Martin
Published: April 2013

On the eighth of April 1978 Tadeusz Kantor was awarded the Rembrandt Prize for outstanding contributions to art. It might be expected that an artist, upon public recognition of his greatness, would have something to say concerning the essence of his art that might aid public understanding. However, Kantor's presentation of this manifesto represents a somewhat puzzling performance. Instead of thanking the international panel of the Goethe Foundation for the award, Kantor painted a strange picture of the artist ‘on trial’. The manifesto appears to end with a sort of disappearing act: Kantor stands before his audience and makes seemingly profound statements about fear and the nature of the artist; he attempts to redefine Dada for his audience and suddenly finds that he has turned himself into the accused, has become a schoolboy once again, has forgotten what he had to say and appears to fade away to the nothingness of the closing ellipsis.This discussion uses Kantor's ‘Little Manifesto’ to explore the problematic of the artist's experience in terms that parallel the concepts that Heidegger and Gadamer developed in their philosophy. It draws on certain themes from post-Heideggerian philosophy, in particular, Agamben's account of negativity in the metaphysics of presence and his radical critique of aesthetics. I will further suggest that, as well as providing a useful framework for ‘understanding Tadeusz Kantor’, such a philosophical hermeneutic framework resonates productively with Kantor's own aesthetic and metaphysical concerns in a way that more conventional frameworks based on the idea of art-as-representation do not.In his regression to childhood from the defiant stance at the beginning of the manifesto Kantor enacts a move from the status of award-winning artist to something more abject. But, paradoxically, that very state of humiliation in the return to the immaturity of childhood, and of the absence of memory, is a return to potentiality, and, this apparently humiliating regression becomes a potentially positive beginning rather than a humiliating end. As Kantor's ‘poor objects’ became a form of resistance against the threat of annihilation during the occupation, this regression to childhood and the potentiality of the informe of immaturity become a form of resistance, even though futile, against the encroachment of the final annihilation of death. It is as if by embracing the nothingness of forgetfulness as a conscious, intentional gesture, Kantor is able to suggest the potential continuation of the performance of himself.
Catastrophe Survived? The Failure of the Tragic in Moira Buffini'sWelcome to Thebes
Authors: Voela Angie
Published: April 2013

In Moira Buffini's Welcome to Thebes (2010) Antigone fails to reach her tragic destiny, the city of Thebes fails to become an autonomous democratic state, and the audience fails to witness the splendour of the ancient heroine. In this paper I consider these three failures as interrelated and dependent upon one another, arguing, along psychoanalytic lines, that they register changing attitudes towards knowledge and the Other which ultimately determine the meaning of ‘failure’. However, in order to better appreciate the contemporary scope of failure, I draw on both Lacan and Baudrillard, highlighting convergences between the two theorists. In particular, I argue that Lacan's notion of the inconsistent Other can be supplemented by Baudrillard's notion of the impossible exchange. Further, the relevance of these notions for theatre and spectatorship is discussed in detail, as they both invite spectators to reflect on their own involvement in the scene they witness and the ontological conditions of (their own) absence and presence. Failure to do so possibly indicates an irreparable loss of the critical capacity which we have always considered central to radical thought.
A Somatechnics of Moralism: New Materialism or Material Foundationalism
Authors: Bruining Dennis
Published: April 2013

A growing number of critical theorists are associating themselves with a movement now commonly referred to as ‘new materialism’. What characterizes this movement, broadly speaking, is a reconceptualization of matter in response to an alleged erasure of materiality in postmodern, poststructuralist, and/or constructivist theories. In this way of thinking, those associated with the so-called ‘linguistic turn’ are said to have upheld (and reinforced) the dichotomy of nature/culture by focusing on culture to the detriment of ‘nature’. However, in this paper, I will argue that new materialist texts are often founded upon and supported by a problematic moralistic rhetoric. Employing a somatechnic framework, I will show that the ethical investment guiding much of the new materialism could be thought of as a particular vitalism, or rather, as I am conceiving it, a material foundationalism, in which matter possesses an inherent life-force.
Getting Emotional After Sex: Tendencies in Queer Studies Browne, Kath and Nash, Catherine (eds) (2010),Queer Methods and Methodologies: Intersecting Queer Theories and Social Science Research, Ashgate, Farnham and Burlington, 2010. ISBN: 978-0-7546-7843-4, 316 pp., £65.00. Halley, Janet and Parker, Andrew (eds),After Sex? On Writing Since Queer Theory, Duke University Press, Durham and London, 2011. ISBN: 978-0-8223-4909-9, 336 pp., US$24.95.Heckert, Jamie and Cleminson, Richard (eds),Anarchism & Sexuality: Ethics, Relationships and Power, Routledge, Oxon and New York, 2011. ISBN: 978-0415-65818-8, 238 pp., US$42.99.
Authors: Cefai Sarah
Published: April 2013

This article reviews three recent queer studies anthologies: Queer Methods and Methodology: Intersecting Queer Theories and Social Science Research, by Kath Browne and Catherine J. Nash (2010), Anarchism & Sexuality: Ethics, Relationships and Power by Jamie Heckert and Richard Cleminson (2011) , and After Sex? On Writing Since Queer Theory, by Janet Halley and Andrew Parker (2011) . A brief synopsis of the books is followed by discussion on three key observations. First, I discuss the specificity of the queer ‘body’, particularly with regard to the scholarly subjectivity articulated by contributors to these anthologies. Second, I discuss the distillation of queer identity from the field of queer corporeality as a specific move to embrace anti-identitarianism through conceiving identity as fluid. Lastly, questions of queer and identity are reconsidered as methodologically specific and, as such, as entailing sensitivity to the movement of concepts between the different epistemological fields of knowledge called the social sciences and the arts and humanities. Through discussion of these observations, this review aims to stimulate thought and reflection on these texts as responding to and participating in the highly contested institutionalisation of queer studies in the academy.
Embryonic-Derived Olfactory Ensheathing Cells Remyelinate Focal Areas of Spinal Cord Demyelination more Efficiently than Neonatal or Adult-Derived Cells
Authors: Coutts David J. C. , Humphries Charlotte E. , Zhao Chao , Plant Giles W. , Franklin Robin J. M.
Published: April 2013

Transplanted olfactory ensheathing cells (OECs) contribute to functional recovery in a range of CNS injuries by several mechanisms, one of which is potentially their ability to form myelin sheaths. OECs sourced from donors of different ages have been shown to remyelinate in several in vitro and in vivo models. However, the optimal donor age for OEC associated remyelination is unclear. This project directly compared the remyelinating potential of p75 purified OEC transplants from three donor ages. OECs were sourced from the olfactory bulbs of embryonic, neonatal, and adult rats and purified by immunopanning, and their remyelinating potential was directly compared by transplantation into the same adult rat toxin-induced model of spinal cord demyelination. Remyelination efficiency 3 weeks after transplantation was assessed morphologically and by immunostaining. Our results indicate that all donor ages remyelinate; however, this process is most efficiently achieved by embryonic-derived OECs.
ABCG2 Protects Kidney Side Population Cells from Hypoxia/Reoxygenation Injury through Activation of the MEK/ERK Pathway
Authors: Liu Wei-Hui , Liu Hong-Bao , Gao Da-Kuan , Ge Guan-Qun , Zhang Peng , Sun Shi-Ren , Wang Han-Min , Liu Shui-Bing
Published: April 2013

Breast cancer resistance protein 1 (BCRP1/ABCG2) is used to identify the side population (SP) within a population of cells, which is enriched for stem and progenitor cells in different tissues. Here, we investigated the role of extracellular signal-regulated kinase (ERK) 1/2 in the signaling mechanisms underlying ischemic/hypoxic conditions in kidney SP cells. Kidney SP cells were isolated using Hoechst 33342 dye-mediated fluorescein-activated cell sorting and then incubated under hypoxia/reoxygenation (H/R) with or without verapamil, a selective BCRP1/ABCG2 inhibitor. ABCG2 expression, ERK activity, cell viability, metabolic activity, and membrane damage were tested after H/R treatment. To evaluate the role of ERK 1/2 on the expression and function of ABCG2, the expression of mitogen-activated protein kinase (MAPK)/ERK kinase (MEK), which preferentially activates ERK, was upregulated by transfection with the recombinant sense expression vector pcDNA3.1-MEK and downregulated by pretreatment with U0126, a specific MEK inhibitor. We found that hypoxia activated ERK activity in the kidney SP cells but not in non-SP cells both in vitro and in vivo. Overexpression of MEK mimicked hypoxia-induced ABCG2 expression. Contrarily, U0126 inhibited hypoxia- and MEK-upregulated ABCG2 expression. Furthermore, H/R induced significant increases in nuclear, metabolic, and membrane damage in both SP cells and non-SP cells; however, this H/R-induced cytotoxicity was much more severe in non-SP cells than in SP cells. Notably, the viability of kidney SP cells was enhanced by MEK overexpression and inhibited by U0126. Verapamil treatment reversed MEK-induced viability of kidney SP cells. When administered systemically into animals with renal ischemia/reperfusion injury, the SP cells significantly improved renal function, accelerated mitogenic response, and reduced cell apoptosis. However, this improved therapeutic potential of SP cells was significantly reduced by pretreatment with verapamil. Collectively, these findings provide evidence for a crucial role for the MEK/ERK-ABCG2 pathway in protecting kidney SP cells from ischemic/hypoxic injury.
Proteomic Profiling of Secreted Proteins for the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells
Authors: Bal Gürkan , Kamhieh-Milz Julian , Sterzer Viktor , Al-Samman Muhammad , Debski Janusz , Klein Oliver , Kamhieh-Milz Sundrela , Bhakdi Sucharit , Salama Abdulgabar
Published: April 2013

Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the most comprehensive proteomic profiling of the HUVEC secretome and identified 827 different secreted proteins. Two hundred and thirty-one proteins were found in all conditions, whereas 369 proteins were identified only under proinflammatory conditions following IL-1β, IL-3, and IL-6 stimulation. Thirteen proteins including complement factor b (CFb) were identified only under IL-1β and IL-3 conditions and may potentially represent HSPC proliferation factors. The combination of bioinformatics and gene ontology annotations indicates the role of the complement system and its activation. Furthermore, CFb was found to be transcriptionally strongly upregulated. Addition of complement component 5b-9 (C5b-9) monoclonal antibody to the stem cell expansion assay was capable of significantly reducing their proliferation. This study suggests a complement-mediated cross-talk between endothelial cells and HSPCs under proinflammatory conditions.
Mesenchymal Stem Cells Expressing Vasoactive Intestinal Peptide Ameliorate Symptoms in a Model of Chronic Multiple Sclerosis
Authors: Cobo Marién , Anderson Per , Benabdellah Karim , Toscano Miguel G. , Muñoz Pilar , García-Pérez Angélica , Gutierrez Iván , Delgado Mario , Martin Francisco
Published: April 2013

Multiple sclerosis (MS) is a severe debilitating disorder characterized by progressive demyelination and axonal damage of the central nervous system (CNS). Current therapies for MS inhibit the immune response and demonstrate reasonable benefits if applied during the early phase of relapsing–remitting MS (RRMS) while there are no treatments for patients that progress neither to the chronic phase nor for the primary progressive form of the disease. In this manuscript, we have studied the therapeutic efficacy of a cell and gene therapy strategy for the treatment of a mouse model of chronic MS [myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE)]. We used allogenic mesenchymal stem cells (MSCs) as a therapeutic tool and also as vehicle to deliver fully processed 3.3-kDa vasoactive intestinal peptide (VIP) to the peripheral immune organs and to the inflamed CNS. Intraperitoneal administrations of MSCs expressing VIP stopped progression and reduced symptoms when administered at peak of disease. The improvement in clinical score correlated with diminished peripheral T-cell responses against MOG as well as lower inflammation, lower demyelination, and higher neuronal integrity in the CNS. Interestingly, neither lentiviral vectors expressing VIP nor unmodified MSCs were therapeutic when administer at the peak of disease. The increased therapeutic effect of MSCs expressing VIP over unmodified MSCs requires the immunoregulatory and neuroprotective roles of both VIP and MSCs and the ability of the MSCs to migrate to peripheral lymph organs and the inflamed CNS.
Role of Matrix Metalloproteinases in Migration and Neurotrophic Properties of Nasal Olfactory Stem and Ensheathing Cells
Authors: Ould-Yahoui Adlane , Sbai Oualid , Baranger Kévin , Bernard Anne , Gueye Yatma , Charrat Eliane , Clément Benoît , Gigmes Didier , Dive Vincent , Girard Stéphane D. , Féron François , Khrestchatisky Michel , Rivera Santiago
Published: April 2013

Adult olfactory ectomesenchymal stem cells (OE-MSCs) and olfactory ensheathing cells (OECs), both from the nasal olfactory lamina propria, display robust regenerative properties when transplanted into the nervous system, but the mechanisms supporting such therapeutic effects remain unknown. Matrix metalloproteinases (MMPs) are an important family of proteinases contributing to cell motility and axonal outgrowth across the extracellular matrix (ECM) in physiological and pathological conditions. In this study, we have characterized for the first time in nasal human OE-MSCs the expression profile of some MMPs currently associated with cell migration and invasiveness. We demonstrate different patterns of expression for MMP-1, MMP-2, MMP-9, and MT1-MMP upon cell migration when compared with nonmigrating cells. Our results establish a correspondence between the localization of these proteinases in the migration front with the ability of cells to migrate. Using various modulators of MMP activity, we also show that at least MMP-2, MMP-9, and MT1-MMP contribute to OE-MSC migration in an in vitro 3D test. Furthermore, we demonstrate under the same conditions of culture used for in vivo transplantation that OE-MSCs and OECs secrete neurotrophic factors that promote neurite outgrowth of cortical and dorsal root ganglia (DRG) neurons, as well as axo-dendritic differentiation of cortical neurons. These effects were abolished by the depletion of MMP-2 and MMP-9 from the culture conditioned media. Altogether, our results provide the first evidence that MMPs may contribute to the therapeutic features of OE-MSCs and OECs through the control of their motility and/or their neurotrophic properties. Our data provide new insight into the mechanisms of neuroregeneration and will contribute to optimization of cell therapy strategies.
Neurotrophin-3 Accelerates Wound Healing in Diabetic Mice by Promoting a Paracrine Response in Mesenchymal Stem Cells
Authors: Shen Lei , Zeng Wen , Wu Yang-Xiao , Hou Chun-Li , Chen Wen , Yang Ming-Can , Li Li , Zhang Ya-Fang , Zhu Chu-Hong
Published: April 2013

Angiogenesis is a major obstacle for wound healing in patients with diabetic foot wounds. Mesenchymal stem cells (MSCs) have an important function in wound repair, and neurotrophin-3 (NT-3) can promote nerve regeneration and angiogenesis. We investigated the effect of NT-3 on accelerating wound healing in the diabetic foot by improving human bone marrow MSC (hMSC) activation. In vitro, NT-3 significantly promoted VEGF, NGF, and BDNF secretion in hMSCs. NT-3 improved activation of the hMSC conditioned medium, promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, and significantly improved the closure rate of HUVEC scratches. In addition, we produced nanofiber mesh biological tissue materials through the electrospinning technique using polylactic acid, mixed silk, and collagen. The hMSCs stimulated by NT-3 were implanted into the material. Compared with the control group, the NT-3-stimulated hMSCs in the biological tissue material significantly promoted angiogenesis in the feet of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. These results suggest that NT-3 significantly promotes hMSC secretion of VEGF, NGF, and other vasoactive factors and that it accelerates wound healing by inducing angiogenesis through improved activation of vascular endothelial cells. The hMSCs stimulated by NT-3 can produce materials that accelerate wound healing in the diabetic foot and other ischemic ulcers.