bluuebunny/crossref_metadata_2025 huggingface dataset:
A new chromogranin A–dependent angiogenic switch activated by thrombin
Authors: Crippa Luca , Bianco Mimma , Colombo Barbara , Gasparri Anna M. , Ferrero Elisabetta , Loh Y. Peng , Curnis Flavio , Corti Angelo
Published: November 2012

Angiogenesis, the formation of blood vessels from pre-existing vasculature, is regulated by a complex interplay of anti and proangiogenic factors. We found that physiologic levels of circulating chromogranin A (CgA), a protein secreted by the neuroendocrine system, can inhibit angiogenesis in various in vitro and in vivo experimental models. Structure-activity studies showed that a functional anti-angiogenic site is located in the C-terminal region, whereas a latent anti-angiogenic site, activated by cleavage of Q76-K77 bond, is present in the N-terminal domain. Cleavage of CgA by thrombin abrogated its anti-angiogenic activity and generated fragments (lacking the C-terminal region) endowed of potent proangiogenic activity. Hematologic studies showed that biologically relevant levels of forms of full-length CgA and CgA1-76 (anti-angiogenic) and lower levels of fragments lacking the C-terminal region (proangiogenic) are present in circulation in healthy subjects. Blood coagulation caused, in a thrombin-dependent manner, almost complete conversion of CgA into fragments lacking the C-terminal region. These results suggest that the CgA-related circulating polypeptides form a balance of anti and proangiogenic factors tightlyregulated byproteolysis. Thrombin-induced alteration of this balance could provide a novel mechanism for triggering angiogenesis in pathophysiologic conditions characterized by prothrombin activation.
Hemophagocytic lymphohistiocytosis in syntaxin-11–deficient mice: T-cell exhaustion limits fatal disease
Authors: Kögl Tamara , Müller Jürgen , Jessen Birthe , Schmitt-Graeff Annette , Janka Gritta , Ehl Stephan , zur Stadt Udo , Aichele Peter
Published: November 2012

Syntaxin-11 (Stx11), an atypical member of the SNARE protein family, is part of the cytolytic machinery of T and NK cells and involved in the fusion of lytic granules with the plasmamembrane. Functional loss of syntaxin-11 in humans causes defective degranulation and impaired cytolytic activity of T and NK cells. Furthermore, patients with STX11 deficiency develop familial hemophagocytic lymphohistiocytosis type 4 (FHL4), a life-threatening disease of severe hyperinflammation. We established Stx11-deficient mice as an animal model for FHL4. Stx11-deficient mice exhibited severely reduced degranulation and cytolytic activity of CTL and NK cells and developed all clinical symptoms of hemophagocytic lymphohistiocytosis (HLH) after infection with lymphocytic choriomeningitis virus (LCMV). The HLH phenotype was further characterized by hyperactive CD8 T cells and continuous IFN-γ production. However, in contrast to perforin-deficient mice, which represent a model for FHL2, progression of HLH was not fatal. Survival of Stx11-deficient mice was determined by exhaustion of antigen-specific T cells, characterized by expression of inhibitory receptors, sequential loss of effector functions, and finally T-cell deletion. Blockade of inhibitory receptors on T cells in Stx11-deficient mice converted nonfatal disease course into fatal HLH, identifying T-cell exhaustion as an important factor for determination of disease severity in HLH.
Aberrant 3′ oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia
Authors: Hilcenko Christine , Simpson Paul J. , Finch Andrew J. , Bowler Frank R. , Churcher Mark J. , Jin Li , Packman Len C. , Shlien Adam , Campbell Peter , Kirwan Michael , Dokal Inderjeet , Warren Alan J.
Published: November 2012

Key Points

Crystal structure of human USB1 identifies it as a member of the LigT-like superfamily of 2H phosphoesterases. USB1 protects spliceosomal U6 small nuclear RNA from aberrant 3′ oligoadenylation.
Multiple-omic data analysis of Klebsiella pneumoniae MGH 78578 reveals its transcriptional architecture and regulatory features
Authors: Seo Joo-Hyun , Hong Jay Sung-Joong , Kim Donghyuk , Cho Byung-Kwan , Huang Tzu-Wen , Tsai Shih-Feng , Palsson Bernhard O , Charusanti Pep
Published: November 2012

Background

The increasing number of infections caused by strains of Klebsiella pneumoniae that are resistant to multiple antibiotics has developed into a major medical problem worldwide. The development of next-generation sequencing technologies now permits rapid sequencing of many K. pneumoniae isolates, but sequence information alone does not provide important structural and operational information for its genome.

Results

Here we take a systems biology approach to annotate the K. pneumoniae MGH 78578 genome at the structural and operational levels. Through the acquisition and simultaneous analysis of multiple sample-matched –omics data sets from two growth conditions, we detected 2677, 1227, and 1066 binding sites for RNA polymerase, RpoD, and RpoS, respectively, 3660 RNA polymerase-guided transcript segments, and 3585 transcription start sites throughout the genome. Moreover, analysis of the transcription start site data identified 83 probable leaderless mRNAs, while analysis of unannotated transcripts suggested the presence of 119 putative open reading frames, 15 small RNAs, and 185 antisense transcripts that are not currently annotated.

Conclusions

These findings highlight the strengths of systems biology approaches to the refinement of sequence-based annotations, and to provide new insight into fundamental genome-level biology for this important human pathogen.
Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report
Authors: Langan Julie , Martin Daniel , Shajahan Polash , Smith Daniel J
Published: November 2012

Background

“Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined.

Description

We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1–15 to 346.9 mg/day during days 16–30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators.

Conclusions

Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS.
Differences in weight status and energy-balance related behaviors among schoolchildren in German-speaking Switzerland compared to seven countries in Europe
Authors: Herzig Michael , Dössegger Alain , Mäder Urs , Kriemler Susi , Wunderlin Tina , Grize Leticia , Brug Johannes , Manios Yannis , Braun-Fahrländer Charlotte , Bringolf-Isler Bettina
Published: November 2012

Background

Overweight in children and adolescents have increased significantly and are a major public health problem. To allow international comparisons, Switzerland joined the European study ‘ENERGY’ cross sectional survey consortium that investigated the prevalence of overweight and obesity as well as selected dietary, physical and sedentary behaviors of 10–12 years old pupils across seven other countries in Europe. The aims of the present study was to compare body composition and energy-balance related behaviors of Swiss schoolchildren to those of the seven European ENERGY-countries and to analyze overweight and energy-balance related behaviors of Swiss children according to socio-demographic factors.

Methods

A school-based cross-sectional study among 10–12 year old children was conducted in Switzerland and seven other European countries using a standardized protocol. Body height, weight and waist-circumference were measured by trained research assistants. Energy-balance related behaviors –i.e. selected dietary, physical activity and screen-viewing behaviors were assessed by questionnaires. Weight status and behaviors in Switzerland were compared to the seven European ENERGY countries. Within the Swiss sample, analyses stratified by gender, parental education and ethnicity were performed.

Results

Data of 546 Swiss children (mean age 11.6±0.8y, 48% girls) were obtained and compared to the ENERGY- results (N=7.148; mean age 11.5±0.8y, 48% girls). In Switzerland significantly less children were overweight (13.9%) or obese (2.3%) compared to the average across the ENERGY-countries (23.7% and 4.7%, respectively), and were even somewhat lower than the ENERGY countries with the lowest prevalence. Sugar sweetened beverage intakes and breakfast habits of Swiss children did not differ significantly from those of ENERGY. However, the mean time devoted by Swiss children to walking or cycling to school and attending sports activities was significantly higher and screen time significantly lower compared to the other ENERGY-countries. Within the Swiss, sample relatively large and consistent differences were observed between children from native and non-native ethnicity.

Conclusions

The prevalence of overweight and obesity among Swiss children are substantial but significantly lower compared to all other European ENERGY-Partners, probably due to the fact that Swiss children were found to be more active and less sedentary comparing to the rest of the European sample.
Aptasensors for rapid detection of Escherichia coli O157:H7 and Salmonella typhimurium
Authors: Wu Wen-he , Li Min , Wang Yue , Ouyang Hou-xian , Wang Lin , Li Ci-xiu , Cao Yu-chen , Meng Qing-he , Lu Jian-xin
Published: November 2012

Herein we reported the development of aptamer-based biosensors (aptasensors) based on label-free aptamers and gold nanoparticles (AuNPs) for detection of Escherichia coli (E. coli) O157:H7 and Salmonella typhimurium. Target bacteria binding aptamers are adsorbed on the surface of unmodified AuNPs to capture target bacteria, and the detection was accomplished by target bacteria-induced aggregation of the aptasensor which is associated as red-to-purple color change upon high-salt conditions. By employing anti-E. coli O157:H7 aptamer and anti-S. typhimurium aptamer, we developed a convenient and rapid approach that could selectively detect bacteria without specialized instrumentation and pretreatment steps such as cell lysis. The aptasensor could detect as low as 105colony-forming units (CFU)/ml target bacteria within 20 min or less and its specificity was 100%. This novel method has a great potential application in rapid detection of bacteria in the near future.
CD19: a biomarker for B cell development, lymphoma diagnosis and therapy
Authors: Wang Kemeng , Wei Guoqing , Liu Delong
Published: November 2012

The human CD19 antigen is a 95 kd transmembrane glycoprotein belonging to the immunoglobulin superfamily. CD19 is classified as a type I transmembrane protein, with a single transmembrane domain, a cytoplasmic C-terminus, and extracellular N-terminus. CD19 is a biomarker for normal and neoplastic B cells, as well as follicular dendritic cells. CD19 is critically involved in establishing intrinsic B cell signaling thresholds through modulating both B cell receptor-dependent and independent signaling. CD19 functions as the dominant signaling component of a multimolecular complex on the surface of mature B cells, alongside complement receptor CD21, and the tetraspanin membrane protein CD81 (TAPA-1), as well as CD225. Through study of CD19 transgenic and knockout mouse models, it becomes clear that CD19 plays a critical role in maintaining the balance between humoral, antigen-induced response and tolerance induction. This review also summarized latest clinical development of CD19 antibodies, anti-B4-bR (an immunotoxin conjugate), blinatumomab (BiTE), and SAR3419 (huB4-DM4), a novel antibody-drug conjugate.
Active labour market policies in a recession
Authors: Andersen Torben M , Svarer Michael
Published: November 2012

A major labour market challenge following the Great Recession is to avoid an increase in long-term unemployment and thus the structural unemployment rate. Active labour market policies may play an important role in this respect. We consider these issues with outset in Denmark which is a country relying extensively on active labour market policies. It is also characterised by high flows into and out of employment, implying that most unemployment spells are rather short and the unemployment rate is relative low. These features have been maintained despite the crisis, and in this sense the Danish flexicurity model has coped reasonably well with the crisis. The Danish active labour market policies have been continuously changed in light of experience, new knowledge and changes in the labour market situation. This paper reviews and discusses these changes in light of the recession and considers how the labour market has coped with the recession.
Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients: a systematic review and meta-analysis
Authors: Wu Youping , Wang Fei , Fan Xiaohua , Bao Rui , Bo Lulong , Li Jinbao , Deng Xiaoming
Published: November 2012

Introduction

Early diagnosis of sepsis is vital to the clinical course and outcome of septic patients. Recently, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) appears to be a potential marker of infection. The objective of this systematic review and meta-analysis was to evaluate the accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients.

Methods

A systematic literature search of PubMed, Embase and Cochrane Central Register of Controlled Trials was performed using specific search terms (up to 15 October 2012). Studies were included if they assessed the accuracy of plasma sTREM-1 for sepsis diagnosis in adult patients with systemic inflammatory response syndrome (SIRS) and provided sufficient information to construct a 2 X 2 contingency table.

Results

Eleven studies with a total of 1,795 patients were included. The pooled sensitivity and specificity was 79% (95% confidence interval (CI), 65 to 89) and 80% (95% CI, 69 to 88), respectively. The positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 4.0 (95% CI, 2.4 to 6.9), 0.26 (95% CI, 0.14 to 0.48), and 16 (95% CI, 5 to 46), respectively. The area under the curve of the summary receiver operator characteristic was 0.87 (95% CI, 0.84 to 0.89). Meta-regression analysis suggested that patient sample size and assay method were the main sources of heterogeneity. Publication bias was suggested by an asymmetrical funnel plot (P = 0.02).

Conclusions

The present meta-analysis showed that plasma sTREM-1 had a moderate diagnostic performance in differentiating sepsis from SIRS. Accordingly, plasma sTREM-1 as a single marker was not sufficient for sepsis diagnosis in systemic inflammatory patients.
Kidney transplantation: analysis of the expression and T cell-mediated activation of latent TGF-β
Authors: Willet Joseph D P , Pichitsiri Watchara , Jenkinson Sarah E , Brain John G , Wood Katrina , Alhasan Abd A , Spielhofer Julia , Robertson Helen , Ali Simi , Kirby John A
Published: November 2012

T cells activate latent TGF-β by an LSKL peptide-sensitive mechanism, suggesting a role for thrombospondin-1 in T cell differentiation after kidney transplantation.

Activated T cells infiltrate a renal allograft during rejection and can respond to TGF-β within the tubules, causing local differentiation and expression of the αE(CD103)β7 integrin. This study was performed to examine the expression of latent TGF-β within renal allograft tissues and to define a mechanism by which T cells can activate and respond to this latent factor. Rejecting renal allograft biopsy tissues showed increased expression of the latent TGF-β complex, which was localized around the tubules by a mechanism that might involve interaction with heparan sulfate in the basement membrane. A cultured renal TEC line also expressed the latent complex, but these cells did not respond to this form of TGF-β by pSmad 3. However, coculture of these cells with activated T cells induced the expression of CD103, suggesting that T cells can activate and respond to the latent TGF-β associated with TEC. Although activated T cells expressed little cell-surface TSP-1, this was increased by culture with fibronectin or fibronectin-expressing renal TEC. Blockade of TSP-1 using LSKL peptides reduced the potential of activated T cells to differentiate in response to latent TGF-β. This study suggests that penetration of renal tubules by activated T cells leads to increased expression of T cell-surface TSP-1, allowing activation of latent TGF-β sequestered on heparan sulfate within the microenvironment. This mechanism may be important for localized phenotypic maturation of T cells that have infiltrated the kidney during allograft rejection.
The emerging role of protein kinase Cθ in cytoskeletal signaling
Authors: Michalczyk Izabela , Sikorski Aleksander F , Kotula Leszek , Junghans Richard P , Dubielecka Patrycja M
Published: November 2012

Review on the signaling of protein kinase C theta (PKCθ), focusing on signal transduction to cytoskeletal elements critical for cell-type specific responses to stimuli.

Cytoskeletal rearrangements often occur as the result of transduction of signals from the extracellular environment. Efficient awakening of this powerful machinery requires multiple activation and deactivation steps, which usually involve phosphorylation or dephosphorylation of different signaling units by kinases and phosphatases, respectively. In this review, we discuss the signaling characteristics of one of the nPKC isoforms, PKCθ, focusing on PKCθ-mediated signal transduction to cytoskeletal elements, which results in cellular rearrangements critical for cell type-specific responses to stimuli. PKCθ is the major PKC isoform present in hematopoietic and skeletal muscle cells. PKCθ plays roles in T cell signaling through the IS, survival responses in adult T cells, and T cell FasL-mediated apoptosis, all of which involve cytoskeletal rearrangements and relocation of this enzyme. PKCθ has been linked to the regulation of cell migration, lymphoid cell motility, and insulin signaling and resistance in skeletal muscle cells. Additional roles were suggested for PKCθ in mitosis and cell-cycle regulation. Comprehensive understanding of cytoskeletal regulation and the cellular “modus operandi” of PKCθ holds promise for improving current therapeutic applications aimed at autoimmune diseases.
Integrated Flight Scheduling and Fleet Assignment Under Airport Congestion
Authors: Pita João P. , Barnhart Cynthia , Antunes António P.
Published: November 2012

Airport congestion is a major cause for the large delays that currently affect the air transport industry. These delays have huge cost implications—for the U.S. economy these costs were estimated at $32.9 billion in 2007. In this paper, we present a mixed-integer linear optimization model aimed at assisting airlines in the making of integrated flight scheduling and fleet assignment decisions that take aircraft and passenger delay costs explicitly into account. The objective of the model is to maximize the expected profits of an airline that faces a given origin/destination-based travel demand and operates in congested, slot-constrained airports. Both airline competition and airline cooperation are dealt with in the model, though in a simplified manner. The model was applied to a case study involving the main network of TAP Portugal, which comprises 31 airports and 100 daily flight legs. The results obtained through the model suggest that the Portuguese legacy carrier can improve their expected profits significantly, while diminishing the total number of flights and slightly increasing the passengers' average connecting time. The calculation effort involved in the application of the model even on a desktop computer is small enough to allow its real-time utilization in International Air Transport Association scheduling conferences. These findings clearly indicate that the model is a significant addition to the airline planning toolbox.
Optimization-Based Adaptive Large Neighborhood Search for the Production Routing Problem
Authors: Adulyasak Yossiri , Cordeau Jean-François , Jans Raf
Published: November 2012

Operational problems arising in the planning of integrated supply chains have been increasingly studied in the past decade. Among these, the production routing problem (PRP) is a difficult problem that aims to jointly optimize production, inventory, distribution, and routing decisions in order to satisfy the dynamic demand of customers and minimize the overall system cost. This paper introduces an optimization-based adaptive large neighborhood search heuristic for the PRP. In this heuristic, binary variables representing setup and routing decisions are handled by an enumeration scheme and upper-level search operators, respectively, and continuous variables associated with production, inventory, and shipment quantities are set by solving a network flow subproblem. Extensive computational experiments have been performed on benchmark instances from the literature. The results show that our algorithm generally outperforms existing heuristics for the PRP and can produce high-quality solutions in short computing times.
Single-Leg Airline Revenue Management with Overbooking
Authors: Aydın Nurşen , Birbil Ş. İlker , Frenk J. B. G. , Noyan Nilay
Published: November 2012

Airline revenue management is concerned with identifying the maximum revenue seat allocation policies. Because a major loss in revenue results from cancellations and no-shows, overbooking has received significant attention in the literature over the years. In this study, we propose new static and dynamic single-leg overbooking models. In the static case we introduce two models: the first one aims to determine the overbooking limit and the second one is about finding the overbooking limit and the booking limits to allocate the virtual capacity among multiple fare classes. Because the second static model is hard to solve, we also introduce computationally tractable models that give upper and lower bounds on its optimal expected net revenue. In the dynamic case, we propose a dynamic programming model, which is based on two streams of events. The first stream corresponds to the arrival of booking requests and the second one corresponds to the cancellations. We conduct simulation experiments to illustrate the effectiveness of the proposed models.
Branch and Price for the Time-Dependent Vehicle Routing Problem with Time Windows
Authors: Dabia Said , Ropke Stefan , van Woensel Tom , De Kok Ton
Published: November 2012

This paper presents a branch-and-price algorithm for the time-dependent vehicle routing problem with time windows (TDVRPTW). We capture road congestion by considering time-dependent travel times, i.e., depending on the departure time to a customer, a different travel time is incurred. We consider the variant of the TDVRPTW where the objective is to minimize total route duration and denote this variant the duration minimizing TDVRPTW (DM-TDVRPTW). Because of time dependency, vehicles' dispatch times at the depot are crucial as road congestion might be avoided. Because of its complexity, all known solution methods to the DM-TDVRPTW are based on (meta-)heuristics. The decomposition of an arc-based formulation leads to a set-partitioning problem as the master problem, and a time-dependent shortest path problem with resource constraints as the pricing problem. The master problem is solved by means of column generation, and a tailored labeling algorithm is used to solve the pricing problem. We introduce new dominance criteria that allow more label dominance. For our numerical results, we modified Solomon's data sets by adding time dependency. Our algorithm is able to solve about 63% of the instances with 25 customers, 38% of the instances with 50 customers, and 15% of the instances with 100 customers.
Progesterone Use to Reverse the Effects of Mifepristone
Authors: Delgado George , Davenport Mary L
Published: November 2012

Objective:

To present a series of cases demonstrating successful reversal of mifepristone effects in women who chose to reverse the medical abortion process.

Case Reports:

Four of 6 women who took mifepristone were able to carry their pregnancies to term after receiving intramuscular progesterone 200 mg.

Discussion:

Mifepristone has been available in the US since 2000. By 2008, approximately 25% of abortions prior to 9 weeks were accomplished with mifepristone. Some women who take mifepristone wish to reverse the medical abortion process. Progesterone competes with mifepristone for the progesterone receptor and may reverse the effects of mifepristone. A PubMed literature search from 1996 to May 2012 did not reveal any trials or case studies evaluating the efficacy of progesterone use to reverse the effects of mifepristone.

Conclusions:

Health care professionals should be aware of the possible use of progesterone to reverse mifepristone in women who have begun the medical abortion process by taking mifepristone and then change their minds.
Use of Intravenous Lipid Emulsion to Reverse Central Nervous System Toxicity of an Iatrogenic Local Anesthetic Overdose in a Patient on Peritoneal Dialysis
Authors: Lange D Bruce , Schwartz Daniel , DaRoza Gerald , Gair Robert
Published: November 2012

Objective:

To describe a case of severe central nervous system toxicity after an overdose of lidocaine by local infiltration in a peritoneal dialysis patient and subsequent treatment of the toxicity with lipid emulsion.

Case Summary:

A 31-year-old male received an iatrogenic overdose of 1600 mg of lidocaine 2% by infiltration during an attempt to remove and replace a peritoneal dialysis catheter. Within 10 minutes after the last lidocaine injection, the patient exhibited features of local anesthetic toxicity, which included tachycardia, hypertension, shortness of breath, dizziness, and a choking sensation that progressed to hallucinations, dysarthria, and uncoordinated, weak limb movement. Within 10 minutes after administration of a single 1.5-mg/kg intravenous bolus of 20% lipid emulsion, the patient improved dramatically. After observation overnight in a monitored care setting, the patient was discharged home with no apparent neurologic sequelae.

Discussion:

Systemic toxicity due to regional anesthesia with local anesthetic agents such as lidocaine has been well described in the medical literature. The use of lipid emulsion as an antidote to the toxicity of local anesthetics and other lipophilic drugs has been suggested as a valuable intervention in both early, rapidly progressive toxicity, as well as toxicity that is refractory to standard treatment. Patients with advanced chronic kidney disease may be more susceptible to systemic effects of lidocaine due to decreased drug elimination.

Conclusions:

Central nervous system toxicity due to an overdose of lidocaine was quickly reversed by intravenous lipid emulsion in our patient.
Gastroparesis-Associated Refractory Nausea Treated with Aprepitant
Authors: Fahler Jon , Wall Geoffrey C , Leman Bernard I
Published: November 2012

Objective:

To report a case of refractory nausea in a patient with idiopathic gastroparesis successfully treated with aprepitant.

Case Summary:

A 41-year-old female with idiopathic gastroparesis demonstrated by a delayed gastric emptying time experienced significant nausea, vomiting, and abdominal pain. This resulted in numerous hospital admissions and regular outpatient intravenous fluid administration. Over a 3-year period the patient had been treated with numerous agents for nausea and vomiting, including metocfopramide 10 mg 3 times daily, ondansetron 8 mg 2 times daily, and promethazine (various doses from 12.5 to 25 mg orally up to 3 times daily). No treatment tried was either tolerated or effective. As a last option before considering gastric pacing the patient was started on aprepitant 40 mg daily. The patient had a dramatic response to aprepitant and reported that her nausea had decreased significantly after 48 hours of starting the medication (2 doses). She was able to tolerate oral feeding and her need for outpatient intravenous hydration abated. Over the course of 2 months while using aprepitant her gastroparesis symptoms continued to improve. She reported no adverse effects attributable to aprepitant. After the first 2 months of aprepitant treatment, the patient was unable to continue the medication due to cost. Although her symptoms did worsen after discontinuation, they did not return to their initial severity. At 4 months after the trial of aprepitant, she continued to have improved symptoms. She claimed not to have daily nausea or vomiting, but still required high-dose promethazine and occasional outpatient intravenous fluids. At that point, she had gained 7.2 kg from the time that she had started aprepitant.

Discussion:

Aprepitant, a neurokinin-1 receptor antagonist, is approved in the US for nausea and vomiting associated with surgery and cancer chemotherapy. To our knowledge, this is the second reported case of its use in gastroparesis-induced nausea. Our patient reported relief of nausea and vomiting despite existing evidence showing that aprepitant has no significant effect on accelerating gastric emptying. Despite its acquisition cost, our patient avoided hospital admission and the administration of intravenous hydration, suggesting aprepitant may be cost-effective in this case.

Conclusions:

Aprepitant may have some utility in treating refractory nausea caused by gastroparesis. This case suggests that the drug's antiemetic effect may be successfully used in areas not approved by the Food and Drug Administration. A controlled trial examining aprepitant in patients with such challenging clinical conditions may be warranted.
Discussions on the Daybook Style and the Formulae of Malediction and Benediction Stemming from Five Middle Kingdom Rock-Cut Stelae from Gebel el-Girgawi
Authors: Hsieh Julia
Published: November 2012

A small corpus of Gebel el-Girgawi inscriptions dated to the Middle Kingdom shows that the beginnings of the Daybook tradition may be placed as early as the First Intermediate Period. Grammatical constructions pertaining to the Daybook style are evidenced in expeditionary and military inscriptions as well as in other types of record keeping, and the presence of such constructions in these seemingly short and insignificant private rock inscriptions may in fact reflect the monumentalization of the diaries of private individuals. Examination of these Gebel el-Girgawi inscriptions also add to the study of benediction/malediction formulae in personal inscriptions outside of the mortuary realm. The use of malediction formula in these inscriptions provides important evidence for the evolution of the malediction/benediction formulae in a non-mortuary context: from its first applications in military and expeditionary graffiti, to its incorporation in royal boundary stelae of the Middle and New Kingdoms.
A Debated but Little Examined Mathematical Text: Papyrus Berlin 6619
Authors: Miatello Luca
Published: November 2012

This paper proposes an updated analysis of the four mathematical problems on the two main fragments of P. Berlin 6619. Photographs, transcription, translation and commentary of the problem texts are included. The analysis focuses in particular on problem 1, on the recto of the large fragment, previously interpreted as the calculation of the sides of two squares. The sentence jr.t HAy.t m wa r nHH (...) indicates that the problem concerns the calculation of two sides of a rectangle. This interpretation is supported also by architectural and cross-cultural parallels.
Processing and Disposal of Radioactive Waste: Selection of Technical Solutions
Authors: Ojovan Michael I. , Drace Zoran
Published: November 2012

An overview of selection criteria for waste processing and disposal technologies is given. A systematic approach for selection of an optimal technology is proposed. Optimal selection of a technical processing and disposal option is case specific to the waste management needs. Waste streams considered are from nuclear applications, research, power generation, nuclear fuel cycle activities and decommissioning of nuclear facilities as well as for NORM-containing waste.
Simulation by classical molecular dynamics of the influence of radiation effects on the fracture behavior of simplified nuclear glasses
Authors: Kieu Le-Hai , Delaye Jean-Marc , Stolz Claude
Published: November 2012

Classical molecular dynamics simulations were used to compare the fracture behavior of pristine and disordered specimens of a simplified nuclear glass. The disordered specimen is prepared in order to mimic the effects of accumulating displacement cascades. It is characterized by a decreasing Boron coordination and an increasing Na concentration in a modifying role. We observe an enhancement of the plasticity of the disordered glass and a decrease of the elastic limit, resulting in greater fracture toughness. The simulation findings are consistent with experimental results.
A Comparison of Consolidation Routes for Halide Containing Wastes
Authors: Mallinson Phillip M. , Fong Shirley K. , Vance Eric R. , Phillips James D.
Published: November 2012

Research has been carried out to optimize the consolidation stage for the immobilization of pyrochemical wastes with a sodium aluminophosphate glass. The alternative techniques of hot pressing and hot isostatic pressing of the calcined wastes with the glass have been investigated. This has been performed on simulant waste material and the products investigated by scanning electron microscopy and X‑ray diffraction. The consolidation techniques were compared to each other and to the original process for suitability as a waste-form.
An overview of research activities on cementitious materials for radioactive waste management
Authors: Drace Zoran , Mele Irena , Ojovan Michael I. , Abdel Rahman R. O.
Published: November 2012

An overview is given on research activities on cementitious materials for radioactive waste management systems based on the IAEA Coordinated Research Project (CRP) held in 2007-2010. It has been joined by 26 research organizations from 22 countries which shared their research and practical activities on use of cementitious materials for various barrier purposes. The CRP has initially formulated the research topics considered within four specific streams: A) Conventional cementitious systems; B) Novel cementitious materials and technologies; C) Testing and waste acceptance criteria; and D) Modelling long term behaviour.

The CRP has analysed both barrier functions and interactions envisaged between various components with focus on predisposal stage of waste management. Cementation processes have achieved a high degree of acceptance and many processes are now regarded as technically mature. A large body of information is currently available on proven waste conditioning technologies although novel approaches are continuing to be devised.

Most of the existing technologies have been developed for conditioning of large amounts of operational radioactive waste from nuclear power plants and other nuclear fuel cycle facilities. However new waste streams including those resulting from legacy and decommissioning activities required improved material performance and technologies.

The most important outcome of CRP was the exchange of information and research co-operation between different institutions and has contributed towards general enhancement of safety by improving waste management practices and their efficiency. The paper presents the most important results and trends revealed by CRP participants. The research contributions of participating organizations will be published as country contributions in a forthcoming IAEA technical publication.
Modelling of the evolution of iron passivity: solving the moving boundaries problem
Authors: Martin Frantz A. , Bataillon Christian
Published: November 2012

In the framework of long term prediction of corrosion in French geological repository systems, the modelling of the time evolution of the corrosion rate of iron over centuries is of high matter. The DPCM (Diffusion Poisson Coupled Model), implemented with the fully implicit CALIPSO numerical code can give access to the evolution of the oxide thickness grown on iron and the resulting corrosion rate. DPCM parameters for outer interfacial reactions have been set to fit to XANES experimental data provided by literature, and then the parameters for inner reaction rates have been evaluated from fitting to ellipsometry results taken from literature. The result is a good average fitting of the model to the experimental data.
Sorption of Pu(IV) and Tc(IV) on concrete and mortar and effect of the complexation by isosaccharinic acid.
Authors: Rojo H. , García-Gutiérrez M. , Missana T. , Galán H.
Published: November 2012

Batch sorption experiments were carried out, in a glove box under N2 atmosphere, for analysing the effect of increasing ISA (isosaccharinic acid) concentrations on sorption of Tc(IV) and Pu(IV) onto previously characterised Spanish concrete and mortar used in a radioactive waste repository. Results clearly showed that concentrations of ISA around 10-4–10-3 M are able to decrease the distribution coefficients (Rd) of the tetravalent elements analysed, both on concrete and mortar. The decrease in Rd experimentally observed was approximately 2 orders of magnitude for technetium and between 3 and 5 orders of magnitude for plutonium.
Determining hydraulic properties of concrete and mortar by inverse modelling
Authors: Schneider Sébastien , Mallants Dirk , Jacques Diederik
Published: November 2012

This paper presents a methodology and results on estimating hydraulic properties of the concrete and mortar considered for the near surface disposal facility in Dessel, Belgium, currently in development by ONDRAF/NIRAS. In a first part, we estimated the van parameters for the water retention curve for concrete and mortar obtained by calibration (i.e. inverse modelling) of the van Genuchten model [1] to experimental water retention data [2]. Data consisted of the degree of saturation measured at different values of relative humidity. In the second part, water retention data and data from a capillary suction experiment on concrete and mortar cores was used jointly to successfully determine the van Genuchten retention parameters and the Mualem hydraulic conductivity parameters (including saturated hydraulic conductivity) by inverse modelling.
Modelling of a Generic Near-Surface Disposal System
Authors: Sileo Noelia R. , Fuentes Néstor O.
Published: November 2012

Development of numerical tools for performance assessment studies of radioactive waste disposal facilities, must address the management of the wide-ranging uncertainties associated with the long-term behaviour of these complex systems. Different approaches and assumptions are made in order to identify and describe relationships between the disposal system and its environment. They take into account, among other factors, the uncertainties associated with temporal evolution of the system within a proposed scenario; the landscape changes arising from future human actions, climate and geological events and processes; the relationships between components of the disposal system and its immediate environment; the behaviour and characteristics of radionuclides within the system and their role in contributing to radiation exposure. In all cases, the different scenario-based models are typically used to determine the radiological significance of potential future discharges from waste disposal facilities. However, it is important to keep always in mind that in any specific case, the purpose of developing and/or applying a model may vary from a simple calculation (e.g. to support concept development) to detailed site-specific performance assessment in support of a disposal license application. The assumptions and modelling simplifications that are appropriate to one type of calculation may not be so easily justified in different circumstances. In order to develop the capability of modelling different long-term scenarios for a generic disposal site for low and intermediate level radioactive wastes, implementation of models of both the near-field/geosphere and biosphere were performed using general approaches for geosphere-biosphere interface, with sub-models for the whole system.
Phosphate Inhibition Effect on Chloride-Induced Crevice Corrosion of Alloy 22
Authors: Miyagusuku Marcela , Carranza Ricardo M. , Rebak Raul B.
Published: November 2012

Alloy 22 has been extensively studied regarding its crevice corrosion (CC) resistance both in pure chloride solutions and in solutions containing different oxyanions that may act as inhibitors of crevice corrosion. The scope of this work was to study the general and localized corrosion behavior of Alloy 22 when phosphate ions were added to a 1 M NaCl solution at 90°C. Results from the electrochemical tests indicate that the size of the passive potential range and the localized corrosion repassivation potential value increased in the presence of phosphate ions. Results from creviced specimens showed a strong inhibition effect of phosphate ions on the chloride induced crevice corrosion of Alloy 22. The critical molar concentration ratio (RCRIT = [phosphate]/[Cl]) to inhibit crevice corrosion was 0.3.
Radiocarbon measurements in cemented ion-exchange resins
Authors: Motiejunas Stasys , Vaidotas Algirdas , Mazeika Jonas , Skuratovic Zana , Vaitkeviciene Violeta
Published: November 2012

A large amount of liquid radioactive waste has been generated at the Ignalina Nuclear Power Plant (NPP), Lithuania, during its operation. The contaminated liquids are treated with ion exchange-resins, which will generate significant waste stream for cementation. The cemented waste will be disposed of in a near-surface repository. The preliminary safety assessment uncovered that 14C is the most significant radionuclide affecting long-term safety of the closed repository. The method of combined acid striping and wet oxidation with subsequent catalytic combustion has been applied for 14C measurements in cemented ion-exchange resins. It allows separating organic and inorganic compounds from the same sample. At first, the inorganic fraction was extracted by adding acid to the sample followed by absorption of CO2 in a pair of alkali gas washed traps. The remaining carbon was extracted by application of a strong oxidizer. The preliminary results show that activity concentration of 14C in the solidified waste has an order of magnitude of tens and hundreds Bq per gram.
Development of High Resolution X-Ray CT Technique for Highly-Radioactive Material
Authors: Katsuyama Kozo , Ishimi Akihiro , Maeda Koji , Nagamine Tsuyoshi , Asaga Takeo
Published: November 2012

In order to observe the structural change in the interior of irradiated fuel assembly, the non-destructive post irradiation examination technique using X-ray computer tomography (X-ray CT) was developed.

In this X-ray CT system, the 12 MeV X-ray pulses were used in synchronization with the switch-in of the detector in order to minimize the effects of the gamma ray emissions from the irradiated fuel assembly then clear cross section CT image of irradiated fuel assembly could be successfully obtained. Also, this non-destructive technique can be applied to observe the inner condition of the high radioactive materials such as a radioactive waste.
ThermoChimie, the ANDRA Thermodynamic Database
Authors: Duro Lara , Grivé Mireia , Giffaut Eric
Published: November 2012

ThermoChimie is the thermodynamic data base initially created by ANDRA in 1996, especially designed and qualified for systems of interest for the French high level waste repository concept. This database is supported by an experimental program on actinides and fission products and also on major components of the systems of interest, and it has been continuously updated since its creation. The validation of the database is continuously on-going through geochemical calculations related to the performance assessment of different backfill/buffer materials and/or geological formations. ThermoChimie contains data on major elements (including stability of minerals such as clays, zeolites, cementitious phases), a long list of radioelements, such as actinides and lanthanides, chemotoxic metals, as well as organic and inorganic ligands.
Migration Behaviour of Lanthanides in Compacted Bentonite with Iron Corrosion Product Using Electrochemical Method
Authors: Idemitsu Kazuya , Akiyama Daisuke , Matsuki Yoshihiko , Irie Yusuke , Inagaki Yaohiro , Arima Tatsumi
Published: November 2012

After the closure of a high-level waste repository, corrosion of the carbon steel overpack will occur. The corrosion products can then migrate into bentonite and affect the migration behavior of radionuclides in bentonite. Therefore, electrochemical experiments, with Fe2+ supplied by anodic corrosion of carbon steel, were carried out to study trivalent lanthanides in compacted bentonite. The interface between a carbon steel coupon and bentonite (dry density, 1.5 Mg/m3) was spiked with a tracer solution containing Nd(NO3)3, Eu(NO3)3, Dy(NO3)3, and Er(NO3)3. The carbon steel coupon was connected as the working electrode to a potentiostat and held at a constant potential between -550 and 0 mV (vs. Ag/AgCl reference electrode) for 7 days. A model using dispersion and electromigration could explain the measured profiles in the bentonite specimens. The best-fit electromigration velocity was related to the applied electric potential and was 1.0–3.8 nm/s for Nd, Eu, Dy, and Er ions. For these lanthanides, the best-fit dispersion coefficient was also related to the applied potential and was 0.8–1.6 μm2/s, and the dispersion length was calculated as 0.2 mm from the linear relationship between the dispersion coefficient and electromigration velocity. Finally, the apparent diffusion coefficient for these lanthanides was estimated as 0.6–0.9 μm2/s.
Liquid Low-level Radioactive Waste Treatment by Membrane Processes
Authors: Zakrzewska-Trznadel Grazyna , Harasimowicz Marian , Miskiewicz Agnieszka , Jaworska-Sobczak Agnieszka
Published: November 2012

The first step in the processing of low- and medium-level liquid radioactive waste is the reduction in the volume of liquid containing small concentrations of radionuclides. Various methods for concentration of radioactive waste have been studied and developed at the Institute of Nuclear Chemistry and Technology, including membrane processes. Reverse osmosis was implemented at the Radioactive Waste Management Plant. Other methods such as ultrafiltration, membrane distillation, adsorption and different integrated processes were studied in the scope of national and international projects.

This paper presents the results of research performed at Institute of Nuclear Chemistry and Technology in Warsaw concerning radioactive liquid waste treatment and the programs of implementation of these methods at nuclear centers producing such wastes, as well as the plans for the utilization of the knowledge and experience and designs of schemes for radioactive waste management in future nuclear power industry. The integrated system developed on the basis of research will be a prototype for further implementation.