bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasive EEG studies in tumor‐related epilepsy: When are they indicated and with what kind of electrodes?
Authors: Rosenow Felix , Menzler Katja
Published: December 2013

Patients with tumor‐related epilepsy (TRE) represent an important proportion of epilepsy surgery cases. Recently established independent negative predictors of postoperative seizure outcome are long duration of epilepsy, presence of generalized tonic–clonic seizures, and incomplete tumor resection. In temporal lobe cases, additional hippocampectomy or corticectomy may further improve outcome. Invasive electroencephalography (EEG) recordings (IEEG) may be indicated to guide the resection by defining eloquent cortex (EC) or to determine the extent of potentially magnetic resonance imaging (MRI)–negative epileptogenic tissue. In fact, invasive recordings are reportedly used in up to 10% of patients who are undergoing epilepsy surgery for TRE. Following careful consideration of the concepts underlying epilepsy surgery, the current use of IEEG, and the predictors of outcome in extratemporal and temporal tumors in TRE, we postulate the following> (1) In patients with extratemporal TRE, IEEG is necessary only if the MRI lesion (and if feasible a rim around it) cannot be completely resected because of adjacent or overlapping EC. In these cases, EC should be mapped to determine its relationships to the lesion, the irritative, and seizure‐onset zones in order to maximize the extent of the lesionectomy. (2) In patients with nondominant temporal TRE, data suggest that if epileptogenic tumors (ETs) are encroaching on mesial temporal structures, if epilepsy duration is long, and seizures are frequent and disabling, these structures should be included in the resection. (3) In patients with dominant temporal TRE, we suggest leaving the mesial structures in place if they are functionally and structurally intact and to consider resecting these structures only if they are structurally and functionally abnormal. There is insufficient evidence justifying the use of IEEG to define the extent of the epileptogenic zone in such cases. This should be reserved for cases where an initial lesionectomy has failed.
Optimizing antiepileptic drug treatment in tumoral epilepsy
Authors: Perucca Emilio
Published: December 2013

Between 30% and 50% of patients with brain tumors first present with a seizure, and up to 30% more will develop seizures later. Therefore, optimal management of these patients requires a rational approach to the use of antiseizure medications. Based on current evidence, prophylactic prescription of long‐term antiepileptic drugs (AEDs) in patients with brain tumors in patients who did not present with seizures is not justified. Because of the high risk of recurrence, however, AED treatment should be strongly considered after a single seizure considered to be due to a tumor. Because of the lack of well‐controlled randomized trials, the decision on which AED provides the best risk–benefit ratio in the individual patient is based mostly on physician's judgment rather than sound scientific evidence. In patients who may require chemotherapy, a non–enzyme‐inducing AED is preferred for initial treatment to minimize the risk of drug interactions that impact adversely on the outcome of anticancer chemotherapy. Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase. However, valproic acid may also increase the hematologic toxicity of antineoplastic drugs, presumably by inhibiting their metabolism, and may independently impair hemostasis, which is of some concern for patients who require surgical intervention. Among newer generation AEDs, levetiracetam has a number of advantageous features, including availability of a parenteral formulation, but other agents such as gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide may also be considered. Potentially more effective treatments targeting specific mechanisms of epileptogenesis and ictogenesis are being investigated. Resection of the tumor, radiation therapy, or chemotherapy can bring refractory seizures under control or prolong the duration of seizure freedom, an effect that does not appear to be necessarily related to removal or shrinkage of the tumor mass. In patients with a successfully treated tumor and an overall good prognosis for long‐term survival, gradual discontinuation of AEDs may be considered.
Hypothalamic hamartomas: Optimal approach to clinical evaluation and diagnosis
Authors: Wilfong Angus A. , Curry Daniel J.
Published: December 2013

Hypothalamic hamartomas (HHs) present a difficult medical problem, manifested by gelastic seizures, which are often medically intractable. Although existing techniques offer modest surgical outcomes with the potential for significant morbidity, the relatively novel technique of magnetic resonance imaging (MRI)–guided stereotactic laser ablation (SLA) offers a potentially safer, minimally invasive method with high efficacy for theHHtreatment. We report here on 14 patients with medically refractory gelastic epilepsy who underwent stereotactic frame–based placement of anMR‐compatible laser catheter (1.6 mm diameter) through a 3.2‐mm twist drill hole. A U.S. Food and Drug Administration (FDA)–cleared laser surgery system (Visualase, Inc.) was utilized to ablate theHH, using real‐timeMRIthermometry. Seizure freedom was obtained in 12 (86%) of 14 cases, with mean follow‐up of 9 months. There were no permanent surgical complications, neurologic deficits, or neuroendocrine disturbances. One patient had a minor subarachnoid hemorrhage that was asymptomatic. Most patients were discharged home within 1 day.SLAwas demonstrated to be a safe and effective minimally invasive tool in the ablation of epileptogenicHH. Because use ofSLAforHHis being adopted by other medical centers, further data will be acquired to help treat this difficult disorder.
Epilepsy surgery of focal cortical dysplasia–associated tumors
Authors: Cossu Massimo , Fuschillo Dalila , Bramerio Manuela , Galli Carlo , Gozzo Francesca , Pelliccia Veronica , Casaceli Giuseppe , Tassi Laura , Lo Russo Giorgio
Published: December 2013

The goal of the present study was to evaluate the clinical characteristics and postoperative seizure outcome of epileptogenic tumors associated with focal cortical dysplasias (FCDs) compared to both solitaryFCDtype I and solitary tumors. Particular attention is given toFCDtypeIIIb (tumors associated withFCDtype I), which have been recently classified as a separate entity. We retrospectively reviewed the clinical charts of 1,109 patients who were operated on for drug‐resistant focal epilepsy, including 492 patients with a histologic diagnosis of solitaryFCDI andII(83 and 157 cases, respectively), solitary tumors (179 cases), andFCD‐associated tumors (73 cases, 58 of which met the criteria ofFCD IIIb of the new International League Against Epilepsy [ILAE] classification). The different subgroups were evaluated for clinical characteristics and postoperative surgical outcome. Clinical variables and postoperative seizure outcome of patients with coexisting tumor andFCDs (FCD IIIb and tumor associatedFCD II) were similar to those of patients with a solitary tumor and differed significantly from patients with solitaryFCDs. Nevertheless, tumors associated withFCDs are characterized by a striking male predominance and a higher seizure frequency as compared to solitary tumors. Patients with drug‐resistant focal epilepsy secondary to a solitary tumor or with a tumor‐associatedFCDhave similar basic clinical presentation and postoperative seizure outcome. Nevertheless, the epileptogenic contribution of the associatedFCDs can be crucial, and it needs to be adequately assessed. The impact ofFCDon tumor‐related epilepsy deserves future research in order to optimize the surgical strategies aimed at seizure relief.
Analysis of the antiepileptic, ethosuximide impacts on neurogenesis of rat forebrain stem cells
Authors: Sondossi Kiana , Majdzadeh Maryam , Ghaeli Padideh , Ghahremani Mohammad Hossein , Shafaroodi Hamed , Paknejad Babak , Ostad Seyed Nasser
Published: December 2013

Specific GABAergic interneurons in the hilus are lost in animal models with temporal‐lobe epilepsy (TLE). Some preclinical evidence has indicated that GABAergic cells may provide relief from seizures in these models. This study was aimed to examine the ability of ethosuximide, an anticonvulsant drug, to promote neurogenesis in 3‐day‐old rat forebrain cortex stem cells. Most of the cells were found to be nestin‐positive undifferentiated neural stem cells prior to their exposure to ethosuximide. It was noted that the number and percentage of tubulin β‐III immunopositive neurons were increased after 6 days treatment with ethosuximide. Upon bFGF withdrawal, exposure to ethosuximide differentiated the stem cells to MAP2 positive neural cells (7.18 ± 0.43, 21.766 ± 0.55 and 41.57 ± 0.5 for control, 0.1 and 1 μm, respectively). GABA immunofluorescence images illustrated that ethosuximide increased GABAergic neurons (7.19 ± 0.32, 23.23 ± 0.55, and 46.30 ± 0.44 for control, 0.1 and 1 μm, respectively). Additionally, BrdU immunofluorescence assay showed that ethosuximide‐enhanced nucleus proliferation in the neuronal stem cells. Therefore, the results of this study suggest that ethosuximide may compensate damage caused by seizure attacks and possibly other neuronal loss disorders.
Interactions between CO2 enhancement and N addition on net primary productivity and water‐use efficiency in a mesocosm with multiple subtropical tree species
Authors: Yan Junhua , Zhang Deqiang , Liu Juxiu , Zhou Guoyi
Published: December 2013

Carbon dioxide (CO2) enhancement (eCO2) and N addition (aN) have been shown to increase net primary production (NPP) and to affect water‐use efficiency (WUE) for many temperate ecosystems, but few studies have been made on subtropical tree species. This study compared the responses of NPP and WUE from a mesocosm composing five subtropical tree species to eCO2 (700 ppm), aN (10 g N m−2 yr−1) and eCO2 × aN using open‐top chambers. Our results showed that mean annual ecosystem NPP did not changed significantly under eCO2, increased by 56% under aN and 64% under eCO2 × aN. Ecosystem WUE increased by 14%, 55%, and 61% under eCO2, aN and eCO2 × aN, respectively. We found that the observed responses of ecosystem WUE were largely driven by the responses of ecosystem NPP. Statistical analysis showed that there was no significant interactions between eCO2 and aN on ecosystem NPP (P = 0.731) or WUE (P = 0.442). Our results showed that increasing N deposition was likely to have much stronger effects on ecosystem NPP and WUE than increasing CO2 concentration for the subtropical forests. However, different tree species responded quite differently. aN significantly increased annual NPP of the fast‐growing species (Schima superba). Nitrogen‐fixing species (Ormosia pinnata) grew significantly faster only under eCO2 × aN. eCO2 had no effects on annual NPP of those two species but significantly increased annual NPP of other two species (Castanopsis hystrix and Acmena acuminatissima). Differential responses of the NPP among different tree species to eCO2 and aN will likely have significant implications on the species composition of subtropical forests under future global change.
Pollination of two oil‐producing plant species: Camelina (Camelina sativaL. Crantz) and pennycress (Thlaspi arvenseL.) double‐cropping in Germany
Authors: Groeneveld Janna H. , Klein Alexandra‐Maria
Published: December 2013

Camelina and pennycress are two annual oil‐producing plant species that have recently gained attention as biofuel feedstock crops. Prior to commercial production, information on their breeding and pollination system is essential to ensure sustainable management. We conducted pollination experiments and observed flower visitors in an experimental double‐cropping system in southern Germany. We found that common camelina varieties were mainly self‐pollinated and yield of one variety seemed to benefit from insect visitation, whereas pennycress was predominantly wind pollinated. Camelina showed higher overall visitation rates by insects than pennycress. Flies and wild bees visited both crop species, but honey bees visited camelina only. We conclude that both oil crop species produce yield without pollinators but offer foraging resources for different insect taxa at times when few other crops and native plants are flowering.
Explaining the reductions in Brazilian sugarcane ethanol production costs: importance of technological change
Authors: Chen Xiaoguang , Nuñez Hector M. , Xu Bing
Published: December 2013

Over the period 1975–2010, unit production costs of sugarcane ethanol in Brazil declined by 67%, while the per‐unit processing costs decreased by more than 70%. This article examines the role of various factors that lead to these cost reductions, including learning‐by‐doing (LBD), economies of scale, rising input prices, market competitiveness, and exogenous technological changes. Using the aggregate industry‐level data, we show that the traditional experience curve approach will lead to biased estimate of the learning effect when economies of scale, rising input prices, market competitiveness, and exogenous technological changes are excluded as explanatory variables in explaining these cost reductions. With the inclusion of these variables and LBD, we find that the reductions in production/processing costs of Brazilian sugarcane ethanol were primarily driven by autonomous technological changes and unrelated to LBD. Economies of scale, market competitiveness, and rising input prices had insignificant impacts on the reductions in production/processing costs of sugarcane ethanol over the sample period.
Spatial mapping of building energy demand in Great Britain
Authors: Taylor Simon C. , Firth Steven K. , Wang Chao , Allinson David , Quddus Mohammed , Smith Pete
Published: December 2013

Maps of energy demand from buildings in Great Britain have been created at 1 km square resolution. They reveal the spatial variation of demand for heat and electricity, of importance for energy distribution studies and particularly for bioenergy research given the significant distance‐based restrictions on the viability of bioenergy crops. Maps representing the spatial variation of energy demand for the year 2009 were created using publicly available sub‐national gas and electricity consumption data. A new statistical model based on census data was used to increase the spatial resolution. The energy demand was split into thermal energy (the heat energy required for space heating and hot water) and electricity used for purposes other than heating (nonheating electricity or NHE) and was determined separately for the domestic and nondomestic sectors. ‘Scenario factors,’ representing the fractional change at national level in the demand for heat and NHE, were derived from scenarios constructed by UKERC. These scenarios represent a range of pathways from the present day to 2050. The present work focused on the two cases of greatest relevance, the ‘low carbon’ and ‘additional policies’ scenarios, and factors for both were derived, for the demand types described, for every 5 years between 2000 and 2050. Approximately, future spatial energy demands can be obtained by applying the scenario factors to the base mapping data for 2009.
Casino Revenue Sensitivity to Competing Casinos: A Spatial Analysis of Missouri
Authors: Walker Douglas M. , Nesbit Todd M.
Published: December 2013

Previous studies have examined the relationships among different gambling industries (e.g., casinos, lotteries, and racetracks), with mixed results. Yet, the literature lacks evidence on the extent to which casinos in a particular market compete with each other. No study considers the proximity of competing casinos in its empirical analysis. This analysis uses quarterly casino property‐level revenue data from Missouri, 1997.1–2010.2, and a model with a distance‐adjusted competition scalar to analyze how competing casinos affect the revenues of a particular casino. The results indicate that machine games, table games, and square footage all have a positive effect on own‐casino revenues. Machine games and square footage have a negative impact on competing casinos; however, table games have a positive impact on competing casinos. These results are consistent with how the Missouri casino industry is developing, with more emphasis on machine games and less on table games. The results suggest that casinos are competitive in nature (i.e., are substitutes), as there is no evidence to suggest that there is any positive agglomeration effect from casinos being clustered. This analysis should be of interest to industry and policy makers, and provides a foundation for further research on the U.S. casino industry.
In vitro anti‐hydroxyl radical activity of the fructooligosaccharides 1‐kestose and nystose using spectroscopic and computational approaches
Authors: Pejin Boris , Savic Aleksandar G. , Petkovic Milena , Radotic Ksenija , Mojovic Milos
Published: December 2013

Fructooligosaccharides (FOS) are bioactive oligosaccharide fructans with beneficial health effects. Anti‐hydroxyl radical activity is an important factor in the description of antioxidant capacity of any natural product. The aim of this study was to estimate in vitro anti‐hydroxyl radical activity of the FOS 1‐kestose and nystose by electron paramagnetic resonance spectroscopy (EPR) and fluorescence spectroscopy (FS) followed by a theoretical approach based on quantum chemistry calculations. A significant anti‐hydroxyl radical potential of both compounds was observed (72% and 78% by EPR and 69% and 74% by FS, respectively), indicating the nystose to be a more active natural product. In addition, the computational results have confirmed that nystose follows the same pattern previously shown for 1‐kestose, that is, that carbohydrates can react with hydroxyl radical. It is well known that FOS belong to cardioprotective nutraceuticals, so the study may be of some interest to research in heart disease.
Evaluation of the effects of sodium chloride, potassium sorbate, nisin and lysozyme on the probability of growth of Clostridium sporogenes
Authors: Khanipour Elham , Flint Steve H. , McCarthy Owen J. , Golding Matt , Palmer Jon , Tamplin Mark
Published: December 2013

The aim of this study was to evaluate the combined effect of salt (sodium chloride, 0–8% w/v), sorbate (potassium sorbate, 0–4.5% w/v), nisin (0–500 ppm) and lysozyme (0–500 ppm) on the survival of Clostridium sporogenes as a non‐toxigenic surrogate of Clostridium botulinum in terms of the probability of growth by using a central composite rotatable design. The results indicated that salt and sorbate were the most effective factors in preventing the growth of Cl. sporogenes in high‐moisture (>95%) and low‐acid conditions. The probability of growth of Cl. sporogenes in broth was reduced by combinations of salt and sorbate. Nisin and lysozyme had insignificant effects on the probability of growth of Cl. sporogenes (P > 0.05). Lysozyme individually and in combination with nisin had no inhibitory effect on Cl. sporogenes. Overall, the addition of sorbate and lysozyme may allow the salt concentration to be reduced while preventing growth.
Chemical composition, sensory and cooking quality evaluation of durum wheat spaghetti enriched with pea flour
Authors: Padalino Lucia , Mastromatteo Marcella , Lecce Lucia , Spinelli Sara , Contò Francesco , Del Nobile Matteo Alessandro
Published: December 2013

The goal of the study was to obtain spaghetti enriched with pea flour with sensory properties close to conventional pasta. To this aim, the study has been organised in two subsequent trials. In the first, the pea flour amount added to the spaghetti was continuously increased until the overall sensory quality reached its threshold value (pea flour concentration = 15%). In fact, the spaghetti samples supplemented with 15% pea flour (15%S‐P) showed less elasticity, unpleasant colour and higher firmness compared to the control sample (CTRL). The second step was aimed to improve the overall sensory quality of the 15%S‐P spaghetti by means of guar gum (GUAR). The sample with GUAR (15%S‐P/GUAR) showed a pleasant colour, odour and taste. Furthermore, the 15%S‐P/GUAR sample recorded a low starch digestibility value (i.e. 54) and a higher soluble fibre content with respect to the 15%S‐P sample.
Constructing the major biosynthesis pathways for amino acids in the brown planthopper, Nilaparvata lugens Stål (Hemiptera: Delphacidae), based on the transcriptome data
Authors: Wan P‐J. , Yang L. , Wang W‐X. , Fan J‐M. , Fu Q. , Li G‐Q.
Published: December 2013

Nilaparvata lugens is a serious phloem‐feeding pest of rice throughout Asia. Rice phloem sap can meet its nutrition requirement for sugars but not for some essential amino acids such as isoleucine, leucine, methionine, phenylalanine, tryptophan, lysine, arginine and histidine. N. lugens harbours yeast‐like symbionts in mycetocytes formed by abdominal fat body cells. Removal of the symbionts results in negative physiological effects, suggesting that the symbionts play a pivotal role in the nitrogen metabolism. In the present paper, 521 mRNA expressed sequence tags (ESTs) encoding 126 enzymes that were involved in amino acid biosynthesis were identified based on a transcriptome data, reverse transcription (RT)‐PCR and rapid amplification of cDNA ends. Similarity analysis, codon usage bias, along with tissue‐biased expression and phylogenetic analysis of a subset of ESTs, suggest that 437 ESTs out of the 521 originate from symbionts, and the remaining 84 mRNA fragments come from N. lugens. Accordingly, the biosynthesis pathways for 20 amino acids were manually constructed. It is postulated that both N. lugens and its symbiont can independently assimilate ammonia and biosynthesize seven non‐essential amino acids: glutamate; glutamine; aspartate; asparagine; alanine; serine; and glycine. N. lugens and symbiont enzymes may work collaboratively to catalyse the biosynthesis of proline, methionine, valine, leucine, isoleucine, phenylalanine and tyrosine. We infer from this that symbionts function in the biosynthesis of lysine, arginine, tryptophan, threonine, histidine and cysteine. Our data support the previously proposed hypothesis, i.e. the yeast‐like symbionts compensate for, at least partially, the amino acid needs of N. lugens.
Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma
Authors: Chmielewski Markus , Hombach Andreas A. , Abken Hinrich
Published: December 2013

Adoptive T‐cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo‐engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody‐derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T‐cell therapy by modulating the tumor stroma by a CAR T‐cell‐secreted transgenic cytokine like interleukin‐12 (IL‐12). The basic process is that CAR T cells, when activated by their CAR, deposit IL‐12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine‐mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials.
Rapamycin‐resistant effector T‐cell therapy
Authors: Fowler Daniel H.
Published: December 2013

Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) represents a stress test for tumor cells and T cells. Mechanisms exist that allow cells to survive this stress, including suboptimal target block, alternative signaling pathways, and autophagy. Rapamycin‐resistant effector T (T‐Rapa) cells have an altered phenotype that associates with increased function. Ex vivo rapamycin, when used in combination with polarizing cytokines and antigen‐presenting‐cell free costimulation, is a flexible therapeutic approach as polarization to T‐helper 1 (Th1)‐ or Th2‐type effectors is possible. Murine T‐Rapa cells skewed toward a Th2‐type prevented graft rejection and graft‐versus‐host disease (GVHD) more potently than control Th2 cells and effectively balanced GVHD and graft‐versus‐tumor (GVT) effects. A phase II clinical trial using low‐intensity allogeneic hematopoietic cell transplantation demonstrated that interleukin‐4 polarized human T‐Rapa cells had a mixed Th2/Th1 phenotype; T‐Rapa cell recipients had a balanced Th2/Th1 cytokine profile, conversion of mixed chimerism toward full donor chimerism, and a potentially favorable balance between GVHD and GVT effects. In addition, a phase I clinical trial evaluating autologous T‐Rapa cells skewed toward a Th1‐ and Tc1‐type is underway. Use of ex vivo rapamycin to modulate effector T‐cell function represents a promising new approach to transplantation therapy.
Design and development of therapies using chimeric antigen receptor‐expressing T cells
Authors: Dotti Gianpietro , Gottschalk Stephen , Savoldo Barbara , Brenner Malcolm K.
Published: December 2013

Investigators developed chimeric antigen receptors (CARs) for expression on T cells more than 25 years ago. When the CAR is derived from an antibody, the resultant cell should combine the desirable targeting features of an antibody (e.g. lack of requirement for major histocompatibility complex recognition, ability to recognize non‐protein antigens) with the persistence, trafficking, and effector functions of a T cell. This article describes how the past two decades have seen a crescendo of research which has now begun to translate these potential benefits into effective treatments for patients with cancer. We describe the basic design of CARs, describe how antigenic targets are selected, and the initial clinical experience with CAR‐T cells. Our review then describes our own and other investigators' work aimed at improving the function of CARs and reviews the clinical studies in hematological and solid malignancies that are beginning to exploit these approaches. Finally, we show the value of adding additional engineering features to CAR‐T cells, irrespective of their target, to render them better suited to function in the tumor environment, and discuss how the safety of these heavily modified cells may be maintained.
Exploiting the curative potential of adoptive T‐cell therapy for cancer
Authors: Hinrichs Christian S. , Rosenberg Steven A.
Published: December 2013

Adoptive T‐cell therapy (ACT) is a potent and flexible cancer treatment modality that can induce complete, durable regression of certain human malignancies. Long‐term follow‐up of patients receiving tumor‐infiltrating lymphocytes (TILs) for metastatic melanoma reveals a substantial subset that experienced complete, lasting tumor regression – and may be cured. Increasing evidence points to mutated gene products as the primary immunological targets of TILs from melanomas. Recent technological advances permit rapid identification of the neoepitopes resulting from these somatic gene mutations and of T cells with reactivity against these targets. Isolation and adoptive transfer of these T cells may improve TIL therapy for melanoma and permit its broader application to non‐melanoma tumors. Extension of ACT to other malignancies may also be possible through antigen receptor gene engineering. Tumor regression has been observed following transfer of T cells engineered to express chimeric antigen receptors against CD19 in B‐cell malignancies or a T‐cell receptor against NY‐ESO‐1 in synovial cell sarcoma and melanoma. Herein, we review recent clinical trials of TILs and antigen receptor gene therapy for advanced cancers. We discuss lessons from this experience and consider how they might be applied to realize the full curative potential of ACT.
Uncoupling T‐cell expansion from effector differentiation in cell‐based immunotherapy
Authors: Crompton Joseph G. , Sukumar Madhusudhanan , Restifo Nicholas P.
Published: December 2013

Adoptive cellular immunotherapy (ACT) is a potentially curative therapy for patients with advanced cancer. Eradication of tumor in mouse models and humans correlates with both a high dose of adoptively transferred cells and cells with a minimally differentiated phenotype that maintain replicative capacity and multipotency. We speculate that response to ACT not only requires transfer of cells with immediate cytolytic effector function to kill the bulk of fast‐growing tumor but also transfer of tumor‐specific cells that maintain an ability for self‐renewal and the capacity to produce a continual supply of cytolytic effector progeny until all malignant cells are eliminated. Current in vitro methods to expand cells to sufficient numbers and still maintain a minimally differentiated phenotype are hindered by the biological coupling of clonal expansion and effector differentiation. Therefore, a better understanding of the physiologic mechanism that couples cell expansion and differentiation in CD8+ T cells may improve the efficacy of ACT.
Adoptive immunotherapy for cancer
Authors: Ruella Marco , Kalos Michael
Published: December 2013

Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic, potent, and durable clinical responses. This success has led to the broader evaluation of engineered T‐lymphocyte‐based adoptive cell therapy to treat a broad range of malignancies. In this review, we summarize concepts, successes, and challenges for the broader development of this promising field, focusing principally on lessons gleaned from immunological principles and clinical thought. We present ACT in the context of integrating T‐cell and tumor biology and the broader systemic immune response.
A new approach to gene therapy using Sleeping Beauty to genetically modify clinical‐grade T cells to target CD19
Authors: Singh Harjeet , Huls Helen , Kebriaei Partow , Cooper Laurence J. N.
Published: December 2013

The advent of efficient approaches to the genetic modification of T cells has provided investigators with clinically appealing methods to improve the potency of tumor‐specific clinical grade T cells. For example, gene therapy has been successfully used to enforce expression of chimeric antigen receptors (CARs) that provide T cells with ability to directly recognize tumor‐associated antigens without the need for presentation by human leukocyte antigen. Gene transfer of CARs can be undertaken using viral‐based and non‐viral approaches. We have advanced DNA vectors derived from the Sleeping Beauty (SB) system to avoid the expense and manufacturing difficulty associated with transducing T cells with recombinant viral vectors. After electroporation, the transposon/transposase improves the efficiency of integration of plasmids used to express CAR and other transgenes in T cells. The SB system combined with artificial antigen‐presenting cells (aAPC) can selectively propagate and thus retrieve CAR+ T cells suitable for human application. This review describes the translation of the SB system and aAPC for use in clinical trials and highlights how a nimble and cost‐effective approach to developing genetically modified T cells can be used to implement clinical trials infusing next‐generation T cells with improved therapeutic potential.
Genetically engineered donor T cells to optimize graft‐versus‐tumor effects across MHC barriers
Authors: Ghosh Arnab , Holland Amanda M. , van den Brink Marcel R. M.
Published: December 2013

Hematopoietic stem cell transplantation has been used for more than 50 years to combat hematologic malignancies. In addition to being the first stem cell therapy, transplantation has provided evidence for the potent anti‐tumor effects of T cells. Facilitating T‐cell‐based immunity against malignancies requires a careful balancing act between generating a robust response and avoiding off‐target killing of healthy tissues, which is difficult to accomplish using bulk donor T cells. To address these issues, several approaches have been developed, drawing on basic T‐cell biology, to potentiate graft‐versus‐tumor activity while avoiding graft‐versus‐host disease. Current strategies for anti‐tumor cell therapies include: (i) selecting optimal T cells for transfer; (ii) engineering T cells to possess enhanced effector functions; and (iii) generating T‐cell precursors that complete development after adoptive transfer. In this review, we assess the current state of the art in T‐lineage cell therapy to treat malignancies in the context of allogeneic hematopoietic stem cell transplantation.
Zivilgesellschaft und sozialer Basisschutz
Authors: van Ginneken Wouter
Published: December 2013

Auszug

Die Zivilgesellschaft unterstützt voll und ganz das Konzept sozialer Basisschutzniveaus und insbesondere die Annahme der IAO‐Empfehlung (Nr. 202) betreffend den innerstaatlichen sozialen Basisschutz, 2012. Die Verwirklichung sozialer Basisschutzniveaus wird einen großen Schritt nach vorne bei der Verringerung von Armut und Ungleichheit bedeuten und weltweit zur Stärkung der Rechte von Menschen beitragen. Die zivilgesellschaftliche Bewegung ist überzeugt, dass der auf Rechten basierende Ansatz der wirksamste Weg ist zur Ausarbeitung und Verwirklichung sozialer Basisschutzniveaus, die zu mehr Autonomie verhelfen und nachhaltig sind. Bei den menschenrechtlichen Sozialschutzgarantien widmet sie ihre Aufmerksamkeit vier konkreten Punkten: i) der Achtung der Rechte und der Würde von Menschen mit Ansprüchen auf soziale Sicherheit; ii) der umfassenden Beteiligung der Zivilgesellschaft; iii) der allgemeinen Deckung auf der lokalen, nationalen und internationalen Ebene; iv) der besonderen Berücksichtigung schutzbedürftiger Gruppen. Im Anschluss an die 101. Internationale Arbeitskonferenz im Jahr 2012 gründeten 59 Organisationen der Zivilgesellschaft die „Koalition für einen sozialen Basisschutz“, deren zwei Hauptaufgaben folgende sind: die allgemeine Verwirklichung sozialer Basisschutzniveaus auf der lokalen und nationalen Ebene zu überwachen und dazu beizutragen; und das Konzept des sozialen Basisschutzes in der globalen Politikgestaltung zu fördern, beispielsweise in Diskussionen über die Entwicklungsagenda für die Zeit nach 2015.
Überprüfung der Methoden zum Erzielen eines Fortschritts hin zu einer universellen Krankenversicherungsdeckung in Ländern mit Niedrigeinkommen: Erfolg des staatlichen sozialen Basisschutzes
Authors: Scheil‐Adlung Xenia
Published: December 2013

Auszug

Trotz Fortschritten in der Ausweitung der Sozialschutzdeckung sind die meisten Länder mit Niedrigeinkommen immer noch weit entfernt von einer universellen Krankenversicherungsdeckung. Daher werden bis 2015 viele der Verbesserungen im Gesundheitsbereich und wesentliche Millenniumsentwicklungsziele (MDGs) mit grö
ßter Sicherheit nicht erreicht werden. In erster Linie sind die schwächsten Gruppen betroffen: die Armen in Stadt und Land sowie die Arbeitnehmer in der informellen Wirtschaft und deren Familien. Es ist von besonderem Belang, dass der Fortschritt nicht nur beschränkt bleiben, sondern gar ins Gegenteil umgekehrt werden könnte, wenn die Politik weiterhin darin scheitert, die eigentlichen Ursachen der Lücken und Mängel in der Krankenversicherungsdeckung anzugehen. Der Artikel liefert Belege dafür, dass diese Ursachen sowohl innerhalb als auch außerhalb des Gesundheitssektors liegen und eng verbunden sind mit Armut und anderen Formen von Gefährdung. Er vertritt die Ansicht, dass ein nachhaltiger Fortschritt hin zu einer universellen Krankenversicherungsdeckung innerhalb eines geeigneten Zeitrahmens nur erreichbar ist, wenn man sich gleichzeitig auf die folgenden Punkte konzentriert: i) Ausweitung der Krankenversicherungsdeckung und Verbesserung des Zugangs zur benötigten Gesundheitsversorgung, ii) Bereitstellung sicheren Einkommens durch Einkommensbeihilfen für Bedürftige, iii) Lösungen bei Einschränkungen in der Einkommensgenerierung oder Unfähigkeit zur Teilnahme an derselben durch Arbeit und iv) kohärente Maßnahmen im Sozial‐, Wirtschafts‐ und Gesundheitssektor und darüber hinaus zur Linderung der Armut. Solche Maßnahmen können am besten im Kontext des staatlichen sozialen Basisschutzes (SPF – social protection floor) eingeführt werden, die eine minimale Gesundheitsversorgung garantiert und allen Bedürftigen wenigstens eine elementare, lebenslange Einkommenssicherheit bietet. Eine SPF kann dazu beitragen, die Wechselwirkungen zwischen mangelnder Gesundheit, Armut und anderen Gefährdungen und Fortschritten bei der universellen Krankenversicherungsdeckung und weiteren Zielen des Sozialschutzes zu stoppen.
Eine Definition der Angemessenheit mit mehreren Variablen: Herausforderungen und Chancen
Authors: Brimblecombe Simon
Published: December 2013

Auszug

Die Verabschiedung der Empfehlung der Internationalen Arbeitsorganisation über sozialen Basisschutz, 2012 (Nr. 202), zeigt, wie wichtig die Ausweitung der Deckung der sozialen Sicherheit weltweit genommen wird. Damit die positiven Auswirkungen einer Deckungsausweitung maximal genutzt werden können, müssen nicht nur möglichst viele Menschen Leistungen und Dienstleistungen erhalten, die so viele Risiken wie möglich abdecken, sondern die Leistungen müssen auch angemessen sein. Wenn auch nicht ganz ohne Aufwand, so kann doch ein Deckungsniveau definiert und gemessen werden. Die Definition einer angemessene Leistung gestaltet sich hingegen oft schwieriger und beruhte bislang meist auf dem Mass relativer Angemessenheit der Geldleistungen: der Ersatzquote. Angesichts der vielfältigen Ziele, welche die Systeme der sozialen Sicherheit anstreben, erscheint allerdings die Verwendung einer umfassender angesetzten Angemessenheit, die nicht nur die Höhe der Geldleistungen betrachtet, nicht nur viel angebrachter, sondern auch notwendig. In einem Kontext, in dem die finanziellen Zwänge nachweislich stärker sind denn je, untersucht dieser Artikel die Bedeutung des Konzepts der Angemessenheit sowie die Frage, warum eine allgemeinere Betrachtung dieser Art notwendig scheint, damit auch andere Aspekte der Leistungs‐ und Dienstleistungserbringung berücksichtigt werden können. Der Artikel beschreibt, wie eine solche Analyse anhand mehrerer Variablen durchgeführt werden könnte und welches ihre Herausforderungen sind. Durch die Mitberücksichtigung weiterer Ziele der Leistungserbringung – wie etwa die Dienstleistungsqualität, die Sicherheit der Leistungen und die Interaktion mit anderen Akteuren – versucht der Artikel dazu beizutragen, die Debatte weiter zu führen.
Whatever Became of the British?
Authors: McCRONE DAVID
Published: December 2013

Much of the debate about ‘being British’ is driven by the politics of the constitutional future of the United Kingdom. This has led to assertions about the declining impact of Britishness, and how, in the interests of the Union, it might be revived. Data from British and Scottish Social Attitudes surveys show that ‘Britain’ remains an important and meaningful frame of reference, even though people in England and Scotland may not define their prime national identity as British. The relationship between national identity and constitutional preferences is complex. Being ‘strongly Scottish’ is a weak predictor of constitutional preferences because almost all Scots are at the ‘strong’ end of the Scottish scale, whereas saying you are ‘British’ (or not) is a better guide. It is not a matter of choosing to be Scottish or English over being British, but recognising the complexity and inter‐relationships of diverse territorial identities.
(Re)Drawing the Lines on Marriage and Sexuality
Authors: YI JOSEPH
Published: December 2013

The campaign for same‐sex marriage is animated by two, contradictory impulses: a libertarian‐egalitarian strain that continually expands the boundaries of what is publicly legitimate; and a conservative one that seeks to reinforce traditional boundaries. Democratic polities would benefit from public discussion on whether to retain normative, sexual boundaries, and if so, what they should reasonably be. I outline a moderately conservative agenda that would limit public legitimacy to sexually exclusive monogamy (heterosexual or homosexual), but informally tolerate most, consenting, nonconventional sexual practices. A spirit of humility, empathy and tragedy will help us to exercise reasonable judgement as we redraw the lines on marriage and sexuality.
The Road Not Taken and the ‘Bad Faith’ Thesis: Why a Liberal Democrat–Labour Coalition Never Happened in May 2010
Authors: JONES BILL
Published: December 2013

This article examines why a Liberal Democrat‐Labour Coalition did not result from inter‐party negotiations after the General Election in May 2010 and whether the coalition which did emerge was based on a marriage of ‘neo‐liberal minds’, as claimed by Andrew Adonis in his 5 Days in May (Biteback, 2013). Consideration of the available evidence, however, suggests a more nuanced conclusion. It is expected that the 2010 agreement will be revisited in preparation for a possible hung parliament in 2015.
Biomechanical comparison of two implants for the stabilization of incomplete ossification of the humeral condyle lesions in dogs
Authors: Coggeshall Jason D. , Lewis Daniel D. , Fitzpatrick Noel , Conrad Bryan P. , Swanson Katy R. , Kim Stanley E. , Palm Lindsey S. , Tremolada Giovanni , Pozzi Antonio
Published: December 2013

Objective

To compare biomechanical properties of (1) 4.5 mm cortical screws and Fitz Fenestrated Tubular Transcondylar (F2T2) screws; (2) normal humeri and humeri with an intracondylar osteotomy; and (3) humeri with an intracondylar osteotomy stabilized with either a 4.5 mm cortical screw or a F2T2 screw.

Study Design

Cadaveric biomechanical assessment.

Sample Population

4.5 mm cortical screws (n = 10), 5.85 mm F2T2 screws (n = 10), and paired dog humeri (n = 40).

Methods

Cortical and F2T2 screws were loaded to failure in 3‐point bending. Ten pairs of humeri with or without an intracondylar osteotomy were axially loaded to failure. Ten additional pairs of humeri with an intracondylar osteotomy were alternately stabilized with a positional cortical or F2T2 screw and axially loaded to failure.

Results

Mean stiffness, yield load, and failure load was significantly greater (P < .001) for the F2T2 screws compared with cortical screws as well as for intact humeri compared with humeri with an intracondylar osteotomy (P < .001). There were no significant differences in mean stiffness (P = .59), yield load (P = .31), or failure load (P = .24) between humeri with stabilized intracondylar osteotomy.

Conclusion

Isolated F2T2 screws have superior mechanical properties to 4.5 mm cortical screws when loaded in 3‐point bending. Intracondylar osteotomy adversely affected humeral mechanical integrity. Osteotomized humeri stabilized by either screw had comparable mechanical properties.
Ecological correlates of trophic status and frugivory in neotropical primates
Authors: Hawes Joseph E. , Peres Carlos A.
Published: December 2013

Primates are among the most observable and best studied vertebrate order in tropical forest regions, with widespread attention dedicated to the feeding ecology of wild populations. In particular, primates play a key role as frugivores and seed‐dispersal agents for a myriad of tropical plants. Sampling effort by primatologists, however, has been unequally distributed, hampering quantitative comparisons of primate diets. We provide the first systematic review of primate diets, with an emphasis on frugivory, using a comprehensive compilation of 290 unique primate dietary studies from 164 localities in 17 countries across the entire Neotropical realm. We account for sampling effort (standardised as hours) in comparing the richness of fruiting plants recorded in primate diets, and the relative contribution of frugivory to the overall diet in relation to key life‐history traits, such as body mass. We find strong support for the long‐held hypothesis, based on Kay's Threshold, that body size imposes an upper limit on insectivory and a lower limit on folivory, and therefore that frugivory is most important at intermediate body sizes. However, the upper body mass limit of extant neotropical primates, truncated by the post‐Pleistocene megafaunal overkill, has implications for the extent of the frugivory–folivory continuum in extinct lineages. Contemporary threats faced by the largest primates serve as a further warning that the feeding ecology and diet of all neotropical primates remain severely undersampled with regard to the composition and richness of fruits consumed. Indeed, frugivorous primates expected to have the most species‐rich plant diets are amongst those most poorly sampled, exposing implications for our current understanding of primate–plant interaction networks.
Catalyst‐Assisted Growth of Single‐Crystalline Hafnium Carbide Nanotubes by Chemical Vapor Deposition
Authors: Tian Song , Li Hejun , Zhang Yulei , Ren Jincui , Qiang Xinfa , Wang Jie
Published: December 2013

Single‐crystalline hafnium carbide (HfC) nanotubes were synthesized by a one‐step catalyst‐assisted chemical vapor deposition (CVD) method. The typical nanotubes had uniform diameters of ~60 nm and wall thicknesses of ~15 nm and preferentially grew along [201]. From HRTEM/EELS analysis, the growth mechanism based on carbon nanotubes (CNT) tip growth and CNT‐templated reaction was proposed for explaining the formation of HfC nanotubes. According to the mechanism, CNTs were first formed by diffusion of C atoms on the surface of solid Ni catalyst particles. Then, gaseous Hf species reacted with C atoms from CNTs to form HfC nanotubes. During the entire growth process, Hf atoms did not participate in the catalytic reaction. Thus, this process was distinguished from the conventional vapor–liquid–solid process.
Rapid Synthesis of DDR Zeolite at Room Temperature
Authors: Sen Mitali , Bose Ankita , Pal Pameli , Das Jugal K. , Das Nandini
Published: December 2013

In this work, DDR zeolites were synthesized by sonochemical method without the application of any heat energy at room temperature. The synthesized zeolites were characterized by X‐ray diffraction (XRD), infrared (IR) spectral analysis, and field‐emission scanning electron microscopy (FESEM). XRD and IR results showed that phase pure DDR zeolite was started to form at room temperature after 24 h of aging and completed the formation after 5 d of aging. The Brunauer–Emmett–Teller (BET) surface area of the powder was found to be 202 m2/g. The FESEM micrograph and elemental analysis showed that desired atomic ratio of the DDR zeolite was obtained after 5 days of synthesis.
Coloration and Nonlinear Optical Properties of ZnTe Quantum Dots in ZnO–TeO2–P2O5 Glasses
Authors: Du Xi , Zhang Liaolin , Dong Guoping , Sharafudeen Kaniyarakkal , Wen Jian , Chen Dongdan , Qian Qi , Qiu Jianrong
Published: December 2013

ZnO–TeO2–P2O5 glasses were prepared by melt‐quenching method. The color of the glass samples changed from colorless to pale red and dark red with increasing TeO2 content. Coloration mechanism and nonlinear optical properties of ZnO–TeO2–P2O5 glasses have been investigated. Raman spectra and transmission electron microscope measurements indicated the precipitation of ZnTe quantum dots in the glasses and ZnTe quantum dots are the origin of coloration. Z‐scan technique was used to examine the nonlinear optical properties of the glasses. The glass sample with 30 mol% TeO2 exhibits large third‐order nonlinear optical susceptibility of 10−11 esu.