bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Quaternary tephrostratigraphy, Ahklun Mountains, SW Alaska
Authors: Kaufman Darrell S. , Jensen Britta J. L. , Reyes Alberto V. , Schiff Caleb J. , Froese Duane G. , Pearce Nicholas J. G.
Published: January 2012

Radiocarbon‐dated sediment cores from six lakes in the Ahklun Mountains, south‐western Alaska, were used to interpolate the ages of late Quaternary tephra beds ranging in age from 25.4 to 0.4 ka. The lakes are located downwind of the Aleutian Arc and Alaska Peninsula volcanoes in the northern Bristol Bay area between 159° and 161°W at around 60°N. Sedimentation‐rate age models for each lake were based on a published spline‐fit procedure that uses Monte Carlo simulation to determine age model uncertainty. In all, 62 14C ages were used to construct the six age models, including 23 ages presented here for the first time. The age model from Lone Spruce Pond is based on 18 ages, and is currently the best‐resolved Holocene age model available from the region, with an average 2σ age uncertainty of about ± 109 years over the past 14.5 ka. The sedimentary sequence from Lone Spruce Pond contains seven tephra beds, more than previously found in any other lake in the area. Of the 26 radiocarbon‐dated tephra beds at the six lakes and from a soil pit, seven are correlated between two or more sites based on their ages. The major‐element geochemistry of glass shards from most of these tephra beds supports the age‐based correlations. The remaining tephra beds appear to be present at only one site based on their unique geochemistry or age. The 5.8 ka tephra is similar to the widespread Aniakchak tephra [3.7 ± 0.2 (1σ) ka], but can be distinguished conclusively based on its trace‐element geochemistry. The 3.1 and 0.4 ka tephras have glass major‐ and trace‐element geochemical compositions indistinguishable from prominent Aniakchak tephra, and might represent redeposited beds. Only two tephra beds are found in all lakes: the Aniakchak tephra (3.7 ± 0.2 ka) and Tephra B (6.1 ± 0.3 ka). The tephra beds can be used as chronostratigraphic markers for other sedimentary sequences in the region, including cores from Cascade and Sunday lakes, which were previously undated and were analyzed in this study to correlate with the new regional tephrostratigraphy. Copyright © 2012 John Wiley & Sons, Ltd.
Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer
Authors: Yang Guo‐Liang , Zhang Lian‐Hua , Bo Juan‐Jie , Huo Xiao‐Jiao , Chen Hai‐Ge , Cao Ming , Liu Dong‐Ming , Huang Yi‐Ran
Published: January 2012

Background and Objective

High‐mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. HMGB1 overexpression has been reported in a variety of human cancers. However, the clinical significance of HMGB1 expression in bladder cancer (BC) remains unclear. This study is aimed to investigate the correlations between HMGB1 expression and prognosis in patients with BC.

Methods

HMGB1 protein expression in 164 primary BC tissue specimens was analyzed by immunohistochemistry, and its association with clinicopathologic factors and prognosis was also analyzed.

Results

HMGB1 protein had high expression in 87 of 164 cases of BC (53%). HMGB1 overexpression was significantly associated with tumor grade (P < 0.001), and stage (P = 0.001). The Kaplan–Meier survival analysis demonstrated that HMGB1 expression was significantly associated with shorter disease‐free survival and overall survival (both P < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with BC.

Conclusions

HMGB1 might be a new molecular marker to predict the prognosis of patients with BC. J. Surg. Oncol. 2012; 106:57–61. © 2012 Wiley Periodicals, Inc.
Rate constants for hydrogen abstraction by HȮ2 from n‐butanol
Authors: Zhou Chong‐Wen , Simmie John M. , Curran Henry J.
Published: January 2012

Rate constants of hydrogen‐atom abstraction from n‐butanol by the HȮ2 radical have been calculated. Conventional transition state theory employing rigid‐rotor harmonic‐oscillator approximations for all but the torsional degrees of freedom is used with tight transition states. The Pitzer–Gwinn‐like approximation using Fourier fits to internal rotations was applied to determine the one‐dimensional hindered potentials. Asymmetric Eckart barriers were used to model tunneling in one‐dimensional through saddle points. Activation entropies for all of the reaction channels have been determined. Hydrogen bonds formed in the transition states lead to ring structures, which lower the energy barrier and thus an increase in the rate constant for abstraction. Conversely, entropy is lost when the ring structure is formed and this decreases the frequency factor for abstraction; therefore, both of these effect influence the rate constants in opposite ways. Abstraction of an α hydrogen atom is dominant throughout the whole temperature range, and the branching ratio decreases from 96.1% at 500 K to 46.6% at 2000 K. As the carbon chain lengthens, the influence from the OH group lessens and hence δ hydrogens behave in a similar fashion to primary H‐atoms in n‐butane. The estimated uncertainty for the individual rate constants is a factor of 2.5. Computed total, kt, and individual rate constants, based on the CCSD(T)/cc‐pVTZ//MP2/6‐311G(d,p) potential energy surface, in the temperature range of 500–2000 K for n‐butanol + HȮ2 are reported as follows (cm3 mol−1 s−1):

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© 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 155–164, 2012
Effect of weld metal chemistry on stress corrosion cracking behavior of AISI 444 ferritic stainless steel weldments in boiling chloride solution
Authors: Antunes P. D. , Correa E. O. , Barbosa R. P. , Silva E. M. , Padilha A. F. , Guimaraes P. M.
Published: January 2012

The influence of the weld metal chemistry on the susceptibility of AISI 444 ferritic stainless steel (FSS) weldment to stress corrosion cracking (SCC) in hot chloride was investigated by constant load tests and metallographic examination. Two types of filler metal of austenitic stainless steel (E316L and E309L) were used in order to produce fusion zones of different chemical compositions. The SCC test results showed that the interface between the fusion zone (FZ) and the heat affected zone (HAZ) was the most susceptible region to SCC. Results also showed that the AISI 444 stainless steel weldment with E309L weld metal presented the best SSC resistance. Microstructural examinations indicated that the cracks initiated in the weld metal and propagated to the HAZ of the AISI 444 FSS, where the fracture occurred and it was observed a considerable amount of precipitates. Additionally, the higher SCC resistance of the AISI 444 FSS weldment with E309L weld metal may be attributed to the presence of a discontinuous delta‐ferrite network in its microstructure, which acted as a barrier to cracks propagation from the fusion zone to the HAZ/fusion zone interface of AISI 444 FSS. Fractrography analyses showed that the transgranular quasi‐cleavage fracture mode was predominant in the AISI 444 weldment with E316L weld metal and the mixed fracture mode was the predominant in the AISI 444 weldment with E309L weld metal.
A novel method to determine the flow accelerated corrosion rate in the elbow
Authors: Zhu X. L. , Lu X. F. , Ling X.
Published: January 2012

Flow‐accelerated corrosion (FAC) is the most common failure in nuclear power plants. The FAC rate conforms to the experimental results in lab, which are calculated by some other FAC rate prediction models. However, when these models are employed to calculate the FAC rate of the elbow, the result is opposite to actual situation of failure of the elbow. In this paper, a new prediction model is proposed to calculate the flow accelerated corrosion (FAC) rate in the elbow, which combine the steady‐state mass transfer model of electrochemical theory and one‐dimensional galvanic corrosion model. Firstly, the distribution of velocity in the elbow is counted by FLUENT. Secondly, the free corrosion potential and the free corrosion current density are calculated by steady‐state mass transfer model. At last, the novel model is used to obtain the FAC rate of the elbow. The result will show that the FAC rate of the outward bend of the elbow is two‐orders than the inward bend of the elbow. The outward bend of elbow is the defective position, which accords with the statistical result of Kuen Ting et al.
The influence of secondary phase carbide particles on the passivity behaviour of NiTi shape memory alloys
Authors: Neelakantan L. , Monchev B. , Frotscher M. , Eggeler G.
Published: January 2012

The current investigation aims at studying the passivity behaviour of NiTi shape memory alloys with different levels of secondary phase titanium carbide (TiC) particles in an electrolyte of 0.9% sodium chloride at 37 °C. The influence of carbides and thermo‐mechanical treatment/cold working on the passivity breakdown is highlighted. The polarisation studies on the as‐cast and cold worked NiTi with high (0.05 wt%) and low (0.005 wt%) carbon levels show a significant difference in oxide stability. The alloy with extremely low carbon content shows a higher breakdown potential. Higher carbon levels result in higher density of larger TiC and these carbide/matrix interfaces are more susceptible to pitting. The qualitative behaviour of passive layer formed at 0.5 V on the cold worked NiTi alloy with different carbon levels was ascertained by electrochemical impedance spectroscopy (EIS). The oxide on the NiTi alloy with high (0.05 wt%) carbon levels showed lower resistance and poor stability at this condition.
On the free implicative semilattice extension of a Hilbert algebra
Authors: Celani Sergio A. , Jansana Ramon
Published: January 2012

Hilbert algebras provide the equivalent algebraic semantics in the sense of Blok and Pigozzi to the implication fragment of intuitionistic logic. They are closely related to implicative semilattices. Porta proved that every Hilbert algebra has a free implicative semilattice extension. In this paper we introduce the notion of an optimal deductive filter of a Hilbert algebra and use it to provide a different proof of the existence of the free implicative semilattice extension of a Hilbert algebra as well as a simplified characterization of it. The optimal deductive filters turn out to be the traces in the Hilbert algebra of the prime filters of the distributive lattice free extension of the free implicative semilattice extension of the Hilbert algebra. To define the concept of optimal deductive filter we need to introduce the concept of a strong Frink ideal for Hilbert algebras which generalizes the concept of a Frink ideal for posets.
Eventually open action
Authors: Majcher‐Iwanow Barbara
Published: January 2012

We study a natural subclass of continuous actions of Polish groups on Polish spaces which we call eventually open actions. We prove that this property characterizes the actions endowed with a complete system of hereditarily countable invariant structures introduced by Hjorth as a generalization of Scott sentences.
Gorenstein projective and flat complexes over noetherian rings
Authors: Enochs E. , Estrada S. , Iacob A.
Published: January 2012

We give sufficient conditions on a class of R‐modules \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathcal {C}$\end{document} in order for the class of complexes of \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathcal {C}$\end{document}‐modules, \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$dw \mathcal {C}$\end{document}, to be covering in the category of complexes of R‐modules. More precisely, we prove that if \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathcal {C}$\end{document} is precovering in R − Mod and if \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathcal {C}$\end{document} is closed under direct limits, direct products, and extensions, then the class \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$dw \mathcal {C}$\end{document} is covering in Ch(R). Our first application concerns the class of Gorenstein flat modules. We show that when the ring R is two sided noetherian, a complex C is Gorenstein flat if and only if each module Cn is Gorenstein flat. If moreover every direct product of Gorenstein flat modules is a Gorenstein flat module, then the class of Gorenstein flat complexes is covering. We consider Gorenstein projective complexes as well. We prove that if R is a commutative noetherian ring of finite Krull dimension, then the class of Gorenstein projective complexes coincides with that of complexes of Gorenstein projective modules. We also show that if R is commutative noetherian with a dualizing complex then every right bounded complex has a Gorenstein projective precover.
Apathy in Parkinson's disease: Diagnostic and etiological dilemmas
Authors: Starkstein Sergio E.
Published: January 2012

About one‐third of patients with Parkinson's disease (PD) are diagnosed with apathy in cross‐sectional studies. However, once patients with concomitant depression and dementia are excluded, the frequency of apathy drops to 5% to 10%. Several scales have been recommended to rate apathy in PD, but specific psychiatric interviews have not been developed, and recently proposed standardized diagnostic criteria are still in the validation process. Most studies assessing the association between subthalamic deep brain stimulation (STN‐DBS) and apathy have reported a relative increase in the frequency and severity of apathy, although discrepant findings have also been reported. Several mechanisms to explain apathy in PD have been proposed, from dopaminergic imbalances in frontal‐basal ganglia circuits to dysfunction of nondopaminergic circuits and the cingulate gyrus. Future studies should provide reliable and valid instruments to diagnose apathy in PD, and should examine the mechanism of apathy accounting for relevant confounders, such as depression and cognitive deficits, and important contextual factors. Finally, treatment for apathy in PD should not be restricted to psychoactive drugs, but should also include nonpharmacological techniques such as psychotherapy and occupational therapy. © 2012 Movement Disorder Society
Anesthesia Information Management Systems: Past, Present, and Future of Anesthesia Records
Authors: Kadry Bassam , Feaster William W. , Macario Alex , Ehrenfeld Jesse M.
Published: January 2012

Documenting a patient's anesthetic in the medical record is quite different from summarizing an office visit, writing a surgical procedure note, or recording other clinical encounters. Some of the biggest differences are the frequent sampling of physiologic data, volume of data, and diversity of data collected. The goal of the anesthesia record is to accurately and comprehensively capture a patient's anesthetic experience in a succinct format. Having ready access to physiologic trends is essential to allowing anesthesiologists to make proper diagnoses and treatment decisions. Although the value provided by anesthesia information management systems and their functions may be different than other electronic health records, the real benefits of an anesthesia information management system depend on having it fully integrated with the other health information technologies. An anesthesia information management system is built around the electronic anesthesia record and incorporates anesthesia‐relevant data pulled from disparate systems such as laboratory, billing, imaging, communication, pharmacy, and scheduling. The ability of an anesthesia information management system to collect data automatically enables anesthesiologists to reliably create an accurate record at all times, regardless of other concurrent demands. These systems also have the potential to convert large volumes of data into actionable information for outcomes research and quality‐improvement initiatives. Developing a system to validate the data is crucial in conducting outcomes research using large datasets. Technology innovations outside of healthcare, such as multitouch interfaces, near‐instant software response times, powerful but simple search capabilities, and intuitive designs, have raised the bar for users' expectations of health information technology. Mt Sinai J Med 79:154–165, 2012. © 2012 Mount Sinai School of Medicine
Integrating Perioperative Information From Divergent Sources
Authors: Frost Elizabeth A. M.
Published: January 2012

The enormous diversity of physician practices, including specialists, and patient requirements and comorbidities make integration of appropriate perioperative information difficult. Lack of communicating computer systems adds to the difficulty of assembling data. Meta analysis and evidence‐based studies indicate that far too many tests are performed perioperatively. Guidelines for appropriate perioperative management have been formulated by several specialties. Education as to current findings and requirements should be better communicated to surgeons, consultants, and patients to improve healthcare needs and at the same time decrease costs. Means to better communication by interpersonal collaboration are outlined. Mt Sinai J Med 79:3–12, 2012. © 2012 Mount Sinai School of Medicine
Developmental Disability in the Young and Postoperative Cognitive Dysfunction in the Elderly After Anesthesia and Surgery: Do Data Justify Changing Clinical Practice?
Authors: Cottrell James E. , Hartung John
Published: January 2012

The assumption that anesthesia has no serious, long‐term, adverse central nervous system consequences may be true for most patients between 6 months and 60 years of age. However, for patients younger than 6 months or older than 60 years, that status quo assumption is under challenge from a growing body of evidence. Fetuses and newborns appear to be at risk because systems that would enable them to fully recover from the effects of more than 2 hours of anesthesia are still in development. In distinction, the elderly appear to be at risk because systems that once enabled them to fully recover have ever‐diminishing capacity. Even for those between the age of 6 months and 60 years, full recovery may require replacing apoptosed neurons and pruning overabundant dendritic spines…perhaps leaving patients not quite the same person that they were before they were anesthetized.Mt Sinai J Med 79:75–94, 2012.© 2012 Mount Sinai School of Medicine
Long‐Term Outcomes in Elderly Surgical Patients
Authors: Deiner Stacie , Silverstein Jeffrey H.
Published: January 2012

Anesthesia has developed to the point where long‐term outcomes are important endpoints. Elderly patients are becoming an increasingly large part of most surgical practices, consistent with demographic shifts. Long‐term outcomes are particularly important for this group. In this review, we discuss functional outcomes in the elderly. We describe the areas of cognitive change and frailty, both of which are specific to the elderly. We also discuss prevention of surgical infections and emerging evidence around hemodynamic alterations in the operating room and their impact on long‐term outcomes. Mt Sinai J Med 79:95–106, 2012. © 2012 Mount Sinai School of Medicine
Prediction of Rate and Severity of Adverse Perioperative Outcomes: “Normal Accidents” Revisited
Authors: Saubermann Albert J. , Lagasse Robert S.
Published: January 2012

The American Society of Anesthesiologists Physical Status classification system has been shown to predict the frequency of perioperative morbidity and mortality despite known subjectivity, inconsistent application, and exclusion of many perioperative confounding variables. The authors examined the relationship between the American Society of Anesthesiologists Physical Status and both the frequency and the severity of adverse events over a 10‐year period in an academic anesthesiology practice. The American Society of Anesthesiologists Physical Status is predictive of not only the frequency of adverse perioperative events, but also the severity of adverse events. These nonlinear mathematical relationships can provide meaningful information on performance and risk. Calculated odds ratios allow discussion about individualized anesthesia risks based on the American Society of Anesthesiologists Physical Status because the added complexity of the surgical or diagnostic procedure, and other perioperative confounding variables, is indirectly factored into the Physical Status classification. The ability of the American Society of Anesthesiologists Physical Status to predict adverse outcome frequency and severity in a nonlinear relationship can be fully explained by applying the Normal Accident Theory, a well‐known theory of system failure that relates the interactive complexity of system components to the frequency and the severity of system failures or adverse events. Mt Sinai J Med 79:46–55, 2012. © 2012 Mount Sinai School of Medicine
Robust Hurwitz and Schur stability via interval positivity
Authors: Keel L. H. , Stratton T. F. , Bhattacharyya S. P.
Published: January 2012

In this paper, we develop a new approach to computing the entire set of stabilizing controllers for a given continuous‐time linear time‐invariant system by using recent results from interval positivity. The discrete counterpart is also presented. The approaches are based on the sign‐definite decomposition that enables us to deal with functions that are polynomially dependent on the parameters of interests. Copyright © 2012 John Wiley & Sons, Ltd.
Predictors of von Willebrand disease in children
Authors: Sidonio Robert F. , Gunawardena Sriya , Shaw Peter H. , Ragni Margaret
Published: January 2012

Background

Bleeding and bruising are common symptoms for which children are referred to a pediatric hematologist. Although bleeding scores have been validated to quantify bleeding risk in adults, there are no similar definitive data in children. The aim was to describe presenting bleeding symptoms in children and evaluate if these bleeding symptoms were predictive of von Willebrand disease (VWD) or low von Willebrand factor (VWF).

Procedure

We performed a retrospective chart review of consecutive pediatric patients referred for perceived bleeding symptoms to the coagulation clinic at The Children's Hospital of Pittsburgh of UPMC. All underwent a uniform bleeding symptom inventory and hemostatic testing. Single and multiple variable logistic regression models were created to predict either VWD, low VWF, or nonspecific defective platelet aggregation, using the predictor variables of family bleeding history, mucocutaneous bleeding, cutaneous bleeding, and surgical bleeding, based on The International Society on Thrombosis and Hemostasis (ISTH) bleeding definitions.

Results

Of 298 pediatric patients evaluated, 8% had VWD (VWF:RCo and VWF:Ag ≤30 IU/dl) and 34% had low VWF (VWF:RCo and VWF:Ag 30–50 IU/dl). Further, 16% had a nonspecific platelet aggregation disorder, 41% had normal hemostatic testing, and 1% had factor VIII or IX deficiency. In single and multiple variable logistic regression analysis, neither a personal or family bleeding history at presentation, nor the presence of two or more bleeding symptoms were predictive of VWD, low VWF, or nonspecific defective platelet aggregation.

Conclusions

These findings suggest that qualitative assessment of bleeding symptoms alone is not useful in children. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards
Authors: Al‐Kzayer Lika'a Fasih Y. , Sakashita Kazuo , Matsuda Kazuyuki , Al‐Hadad Salma Abbas , Al‐Jadiry Mazin Faisal , Abed Wisam Majeed , Abdulkadhim Jaafar M.H. , Al‐Shujairi Tariq Abadi , Hasan Janan Ghalib , Al‐Abdullah Hussam M. Salih , Al‐Ani Mouroge H. , Saber Paiman Ali I. , Inoshita Toshi , Kamata Minoru , Koike Kenichi
Published: January 2012

Background

Genetic examination of childhood leukemia has not been available in Iraq. We here report the frequency of TEL‐AML1, E2A‐PBX1, MLL‐AF4, and BCR‐ABL chimeric transcripts in 264 Iraqi children newly diagnosed with acute lymphoblastic leukemia (ALL), using FTA cards impregnated with bone marrow aspirate or whole blood.

Patients and methods

The diagnosis of ALL was made according to standard French‐American‐British morphologic criteria. Based on the results of storage temperature and duration, most of the FTA samples were preserved at 4°C for up to 6 weeks in five Iraqi hospitals and then transferred to Japan for molecular analysis. Nested reverse transcription‐polymerase chain reaction was adopted for the analysis.

Results

TEL‐AML1 chimeric transcript product was found in 32 (12.1%) of 264 ALL patients. Eleven (4.2%) patients, 4 (1.5%) patients, and 11 (4.2%) patients had E2A‐PBX1 mRNA, MLL‐AF4 mRNA, and BCR‐ABL mRNA, respectively. One patient had both TEL‐AML1 and E2A‐PBX1 fusion genes. The incidence of TEL‐AML1 in Iraqi ALL children appears to be similar to or slightly higher than those of Jordan (12%) and Kuwait (7%). The prevalence and clinical findings of ALL patients with either E2A‐PBX1 or BCR‐ABL were comparable to the data reported elsewhere.

Conclusion

International collaboration via FTA cards may be helpful to improve diagnosis and management of patients with hematological malignancies in low‐income and underdeveloped countries. Pediatr Blood Cancer 2012;59:461–467. © 2012 Wiley Periodicals, Inc.
Bilateral Wilms tumors (WT) treated with the SIOP 93 protocol in France: Epidemiological survey and patient outcome
Authors: Sudour Hélène , Audry George , Schleimacher Gudrun , Patte Catherine , Dussart Sophie , Bergeron Christophe
Published: January 2012

Background

The treatment of bilateral Wilms tumors (WT) requires multimodality therapy with individualized decision to ensure cure while preserving as much renal parenchyma as possible.

Procedure

We analyzed the clinical records of 49 children with bilateral WT treated in France between 1993 and 2001, according to the SIOP‐93 guidelines (individual treatment program: Treatment was continued as long as there was imaging evidence of tumor regression). Pathology reports, duration of preoperative chemotherapy and surgical records were also reviewed. Overall Survival (OS) and Event‐Free Survival (EFS) rates were studied and relationships between possible prognostic factors and survival were assessed.

Results

Imaging studies revealed bilateral involvement in 98% of the cases. Whatever the response to preoperative chemotherapy, the mean duration of neoadjuvant chemotherapy was 80 days (Q1–Q3: 47–89 days). Forty‐eight children underwent nephron sparing surgery (NSS) at least for one kidney and 19 for both. Five‐year EFS and OS rates were, respectively, 83.4 and 89.5%. Only the most advanced stages were shown to affect OS (P = 0.03). At study endpoint, end‐stage renal disease (ESRD) was reported in seven children, associated with a predisposing phenotype in three.

Conclusions

Results of this study demonstrate a favorable outcome of patients with bilateral WT receiving an individual treatment program. With a tailored approach to treatment according to the tumor response, 77% of our patients were operated before the third month of preoperative chemotherapy. In spite of good survival, 14% of our patients have ESRD. Pediatr Blood Cancer 2012; 59: 57–61. © 2012 Wiley Periodicals, Inc.
Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate
Authors: Nadaraja Sambavy , Mamoudou Aissata Diop , Thomassen Harald , Wehner Peder Skov , Rosthoej Steen , Schroeder Henrik
Published: January 2012

Background

High dose methotrexate (HD‐MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5‐HT3 receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36–42 hours and has higher affinity and selectivity to the 5‐HT3 receptor. Adult studies have demonstrated that palonosetron is both more effective and require fewer administrations than first generation 5‐HT3 receptor antagonists. The purpose of this study was to examine the effect of a single dose of palonosetron (5 µg/kg) for the prevention of chemotherapy‐induced nausea and vomiting in children 18 years of age with ALL treated with HD‐MTX, 5 g/m2.

Procedure

Between January 2010 and December 2010, 138 courses, originating from 53 children, were included from four Danish Childhood Cancer Centers. Information regarding emetic episodes, rescue therapy, and nausea were recorded prospectively on questionnaires.

Results

Complete response (no emesis and no rescue therapy) was achieved in 84.1% of courses during the acute (0–24 hours post‐chemotherapy) and in 60.1% during the delayed phase (24–66 hours post‐chemotherapy). 92.0% of courses were free of emesis during the acute, and 86.2% were free of emesis during the delayed phase. 76.8% of courses were free of nausea during the acute, and 78.3% were free of nausea during the delayed phase.

Conclusions

A single dose of palonosetron—without concomitant corticosteroid—was effective in preventing both acute and delayed phase CINV in majority of children with ALL treated with HD‐MTX. Pediatr Blood Cancer 2012; 59: 870–873. © 2012 Wiley Periodicals, Inc.
The effect of trauma on expressive language impairment in borderline personality disorder
Authors: Carter Phoebe E. , Grenyer Brin F. S.
Published: January 2012

Borderline personality disorder (BPD) is a disorder with known expressive language impairments that may be activated in treatment through interpersonal cues to the trauma memory system of these patients. However, there are few BPD studies investigating this phenomenon empirically. Our previous research is the first known investigation revealing expressive language deficits using clinically relevant trauma‐salient stimuli; the current study extends this to compare specific expressive language deficits on a neutral and emotive stimulus and relationships with trauma history. BPD and matched control (N = 24) verbalizations were analysed by computerized measures of language impairment and pause profiles. BPD subjects evidenced greater overall language impairment and reduced syntactic complexity, but not semantic complexity compared with controls. No such differences were found between the two groups on the neutral condition. BPD subjects utilized significantly higher proportions of pauses for both the emotive and neutral condition. BPD subjects used significantly greater proportions of pauses when generating adjectives related to early relationship with mother, not father. Presence of physical abuse history and PTSD related to some expressive language deficits. These results support neuroimaging findings demonstrating reduced activation of the pre‐frontal cortex or anterior cingulate, alongside increased bilateral activation of the amygdala, during exposure to trauma‐salient stimuli. Copyright © 2012 John Wiley & Sons, Ltd.
The prevalence of personality disorder among ethnic minorities: findings from a national household survey
Authors: Crawford Mike J. , Rushwaya Tendai , Bajaj Priya , Tyrer Peter , Yang Min
Published: January 2012

Studies that have examined the ethnicity of people with personality disorder (PD) in contact with mental health services have generally reported that those from ethnic minorities are under‐represented. However, the relationship between ethnicity and PD in the community is unclear. We therefore conducted a secondary analysis of data from a national household survey of people living in Great Britain to compare levels of PD among people from different ethnic backgrounds. Personality was assessed using the SCID‐II screening questionnaire. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated for the likelihood of people from Black, Asian and other ethnic minority groups having PD. Compared with White subjects, PD was more prevalent among people from Black (OR = 1.44; 95% CI = 1.07–1.96) and other ethnic minority groups (OR = 1.50; 95% CI = 1.07–2.10). These data suggest that in Great Britain, PD is at least as prevalent among Black and other minority ethnic groups as it is among White people. Further efforts need to be made to ensure that people with PD have access to suitable services regardless of their ethnicity. Copyright © 2012 John Wiley & Sons, Ltd.
Critical differences in HIV‐1 and HIV‐2 protease specificity for clinical inhibitors
Authors: Tie Yunfeng , Wang Yuan‐Fang , Boross Peter I. , Chiu Ting‐Yi , Ghosh Arun K. , Tozser Jozsef , Louis John M. , Harrison Robert W. , Weber Irene T.
Published: January 2012

Clinical inhibitor amprenavir (APV) is less effective on HIV‐2 protease (PR2) than on HIV‐1 protease (PR1). We solved the crystal structure of PR2 with APV at 1.5 Å resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR1 mutant (PR1M) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR2. PR1M more closely resembled PR2 than PR1 in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR1M with APV, DRV, and SQV were compared with available PR1 and PR2 complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR1M and PR1, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR1M. Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR1M and PR2 relative to the strong hydrogen bonds observed in PR1, consistent with 15‐ and 19‐fold weaker inhibition, respectively. Overall, PR1M partially replicates the specificity of PR2 and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV‐2.
Bidentate and tridentate metal‐ion coordination states within ternary complexes of RB69 DNA polymerase
Authors: Xia Shuangluo , Eom Soo Hyun , Konigsberg William H. , Wang Jimin
Published: January 2012

Two divalent metal ions are required for primer‐extension catalyzed by DNA polymerases. One metal ion brings the 3′‐hydroxyl of the primer terminus and the α‐phosphorus atom of incoming dNTP together for bond formation so that the catalytically relevant conformation of the triphosphate tail of the dNTP is in an α,β,γ‐tridentate coordination complex with the second metal ion required for proper substrate alignment. A probable base selectivity mechanism derived from structural studies on Dpo4 suggests that the inability of mispaired dNTPs to form a substrate‐aligned, tridentate coordination complex could effectively cause the mispaired dNTPs to be rejected before catalysis. Nevertheless, we found that mispaired dNTPs can actually form a properly aligned tridentate coordination complex. However, complementary dNTPs occasionally form misaligned complexes with mutant RB69 DNA polymerases (RB69pols) that are not in a tridentate coordination state. Here, we report finding a β,γ‐bidentate coordination complex that contained the complementary dUpNpp opposite dA in the structure of a ternary complex formed by the wild type RB69pol at 1.88 Å resolution. Our observations suggest that several distinct metal‐ion coordination states can exist at the ground state in the polymerase active site and that base selectivity is unlikely to be based on metal‐ion coordination alone.
The impact of CRISPR repeat sequence on structures of a Cas6 protein–RNA complex
Authors: Wang Ruiying , Zheng Han , Preamplume Gan , Shao Yaming , Li Hong
Published: January 2012

The repeat‐associated mysterious proteins (RAMPs) comprise the most abundant family of proteins involved in prokaryotic immunity against invading genetic elements conferred by the clustered regularly interspaced short palindromic repeat (CRISPR) system. Cas6 is one of the first characterized RAMP proteins and is a key enzyme required for CRISPR RNA maturation. Despite a strong structural homology with other RAMP proteins that bind hairpin RNA, Cas6 distinctly recognizes single‐stranded RNA. Previous structural and biochemical studies show that Cas6 captures the 5′ end while cleaving the 3′ end of the CRISPR RNA. Here, we describe three structures and complementary biochemical analysis of a noncatalytic Cas6 homolog from Pyrococcus horikoshii bound to CRISPR repeat RNA of different sequences. Our study confirms the specificity of the Cas6 protein for single‐stranded RNA and further reveals the importance of the bases at Positions 5–7 in Cas6–RNA interactions. Substitutions of these bases result in structural changes in the protein–RNA complex including its oligomerization state.
PERSISTING EFFECTS OF RIVER REGULATION ON EMERGENT AQUATIC INSECTS AND TERRESTRIAL INVERTEBRATES IN UPLAND FORESTS
Authors: Jonsson M. , Deleu P. , Malmqvist B.
Published: January 2012

River regulation can alter the structural complexity and natural dynamics of river ecosystems substantially with negative consequences for aquatic insects. However, there have been few studies of regulation effects on the export of emergent insects into terrestrial ecosystems. In northern Scandinavia, we compared emerged aquatic insect and terrestrial invertebrate biomass between four strongly regulated and four free‐flowing rivers using fortnightly measurements at three upland‐forest blocks in each over one summer. The biomass of emerged aquatic insects was significantly lower along regulated rivers than free‐flowing rivers. Biomass in Linyphiidae, Opiliones, Staphylinidae, total Coleoptera, Formicidae and total terrestrial invertebrates was also lower along regulated rivers. Aquatic insect biomass did not explain the entire regulation effect on terrestrial invertebrates but did explain significant variations among Linyphiidae, total Coleoptera, Formicidae and total terrestrial biomass. Variations in Formicidae also explained significant variance among several terrestrial taxa, suggesting some keystone role in this group. Overall, our results suggest that river regulation affects upland‐forest invertebrate communities, with at least some of these effects arising from links between aquatic emergence and terrestrial predators. The data highlight the need to consider areas beyond the riparian zone when assessing the effects of river regulation. Copyright © 2012 John Wiley & Sons, Ltd.
Patterns, processes, and impacts of abrupt climate change in a warm world: the past 11,700 years
Authors: Shuman Bryan
Published: January 2012

Abrupt environmental changes punctuated the warm Holocene epoch (the past ∼11,700 years), and studies of these episodes can provide insight into the dynamics that produce rapid climate changes, as well as their ecologic, hydrologic, and geomorphic impacts. This review considers the processes that generated warm world abrupt changes and their landscape and resource effects, including nonlinear climate system interactions, as well as the possibility that large climate variability can linearly produce apparent ‘state shifts.’ Representative examples of Holocene changes illustrate processes that could produce future changes, including (1) rapid changes in ice sheets, such as by ca 8200 years before AD 1950, (2) shifts in the behavior of the El Nino‐Southern Oscillation (e.g., at ca 5600 years before AD 1950) and Atlantic Meridional Overturning Circulation (e.g., at ca 2700 years before AD 1950), and (3) land–atmosphere feedbacks, such as were possible in North Africa in the mid‐Holocene. These case examples, drawn primarily from the Northern Hemisphere, also reveal the dynamics that generate the types of climate change impacts that would be particularly evident to individuals and societies, such as rapid tree species declines (observed to have taken place within as little time as 6–40 years) and persistent shifts in the regional availability of water. Holocene changes also demonstrate that even progressive climate change can produce important abrupt impacts; that increased rates of background climate forcing may increase the frequency of abrupt responses; and that impacts may well depend upon the particular sequence of changes. WIREs Clim Change 2012, 3:19–43. doi: 10.1002/wcc.152

This article is categorized under:

Paleoclimates and Current Trends > Paleoclimate
Offshore support structure optimization by means of integrated design and controls
Authors: Fischer T. , de Vries W. , Rainey P. , Schmidt B. , Argyriadis K. , Kühn M.
Published: January 2012

Support structures are one of the main cost drivers offshore, and since other offshore rules apply with regards to design and site conditions, different methodologies have to be developed to mitigate the loads on the support structure and therefore to reduce the associated component costs. Detailed onshore studies and field tests have already shown that advanced control algorithms can be an effective way to reduce fatigue and extreme loading on a wind turbine. Still, the overall cost‐effectiveness for large offshore wind farms has not been studied in detail yet. In the scope of this paper, studies of new controller concepts are integrated within the design process of offshore support structures in order to stretch the applicability of monopiles to larger water depths or simply to reduce the structural weight and associated costs.

A reference design of the support structure is made for a site in the Dutch North Sea. The focus is on reducing the dominant hydrodynamic excitation on the support structure. The implemented load mitigation concept leads to significant reductions in loading, allowing considerable material savings and therefore a more cost‐effective design. The presented approach allows material reductions of more than 9% for the studied support structure. Undesired side effects, such as increased wear of turbine components, are unlikely, as other system loadings and characteristics remain within an acceptable range. Even if some of the rotor–nacelle assembly loads are slightly increased by the applied controller, the increases are low and probably still within the margins of the type‐class fatigue loads. Copyright © 2012 John Wiley & Sons, Ltd.
Role of purinergic P2X receptors in the control of liver homeostasis
Authors: Fausther Michel , Gonzales Emmanuel , Dranoff Jonathan A.
Published: January 2012

It is now accepted that extracellular ATP and other nucleotides are potent signaling molecules, akin to neurotransmitters, hormones, and lipid mediators. In the liver, several clues support a significant role for extracellular ATP‐induced signaling pathways in the control of tissue homeostasis. First, ATP and other nucleotides are physiologically detected in extracellular fluids within the liver, including sinusoidal blood and intraductular bile, in various mammalian species including human and rodents. Moreover, finely tuned mechanisms of ATP release by different liver cell types have been described, under physiological cellular changes. In addition, most hepatic cells constitutively express, at the membrane level, several ATP‐metabolizing ectoenzymes and ATP‐sensitive receptors that modulate and transduce these mediator signals, respectively. Finally, hepatic cells also express numerous membrane transporters that actively contribute to purinergic salvage pathways. Once released in the extracellular medium, unmetabolized ATP molecules can bind to purinergic P2X and P2Y receptors, and subsequently trigger various intracellular signal transduction pathways collectively referred to as purinergic signaling. In the liver, purinergic signaling has been shown to regulate key basic cellular functions, such as glucose/lipid metabolism, protein synthesis and ionic secretion, and homeostatic processes, such as cell cycle, inflammatory response, and immunity. While the functional relevance of P2Y receptors in liver physiology has been well documented, limited information is available regarding the potential role of hepatic P2X receptors in the modulation of liver homeostasis. WIREs Membr Transp Signal 2012,1:341–348. doi: 10.1002/wmts.32

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Metabotropic signaling by kainate receptors
Authors: Rodrigues Ricardo J. , Lerma Juan
Published: January 2012

Kainate receptors (KARs) are members of the ionotropic glutamate receptor family. Despite their ubiquitous presence in the central nervous system, and in contrast to the better characterized N‐methyl‐d‐aspartates (NMDARs) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors (AMPARs), the contribution of KARs to synaptic transmission has only been demonstrated in a few central synapses. However, there is now accumulating evidence that KARs are present on both sides of the synapse, where they play distinct and diverse roles. In addition to their contribution to synaptic transmission, KARs can regulate synaptic activity and plasticity either by presynaptically modulating neurotransmitter release at GABAergic and glutamatergic synapses, or by postsynaptically regulating neuronal excitability. This prominent neuromodulatory role of KARs has been further highlighted by the finding that these glutamate‐gated ion‐channels can also signal through G‐proteins and other second messengers. This non‐canonical metabotropic signaling of KARs was firmly established by demonstrating it to be independent of ion flux. The discovery of this dual signaling capacity of KARs constituted a breakthrough in understanding how they function and since then, an increasing number of metabotropic actions of KARs have been reported. It is now clear that this dual signaling underlies the diverse functions of KARs and defining this metabotropic component of the signaling system operated by KARs will be necessary to understand the physiological contributions of glutamate receptors. WIREs Membr Transp Signal 2012, 1:399–410. doi: 10.1002/wmts.35

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Plant and fungal photopigments
Authors: Heintzen Christian
Published: January 2012

Light is both an energy source and a carrier of information. Changes in light intensity, direction, quality, spectral composition, and the metronomic predictability of the Earths' light‐dark cycles carry vital information about the environment. Photoreceptors have evolved that sense these characteristics of light and trigger cellular signaling processes that control physiology, development, and behavior and enable organisms to develop a sense of space and time. In plants and fungi the photoreceptive rhodopsins, light oxygen voltage proteins, phytochromes and cryptochromes sense changes in and facilitate the adaptation to the light environment. WIREs Membr Transp Signal 2012, 1:411–432. doi: 10.1002/wmts.36

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