bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term cardiac follow‐up of children treated with anthracycline doses of 300 mg/m2 or less for acute lymphoblastic leukemia
Authors: Rathe Mathias , Carlsen Niels Lauritz Torp , Oxhøj Henrik , Nielsen Gunner
Published: October 2009

Background

The cardiotoxic effect of anthracyclines has been well described for moderate to high cumulative doses (>350 mg/m2). However, the question of whether sub‐clinical signs of cardiomyopathy may develop and progress over time in children receiving doses of <350 mg/m2 is controversial. The aim of the present study was to examine cardiac function with serial echocardiography from diagnosis to last follow‐up, relapse, or death, and to investigate whether suspected risk factors (e.g., age at diagnosis, gender, cumulative dose, and length of follow‐up) had a significant influence on cardiac function.

Procedure

An unselected cohort of 80 patients treated with multi‐drug chemotherapy including anthracycline doses of 300 mg/m2 or less for childhood acute lymphoblastic leukemia was followed with serial echocardiograms. The deviations of each echocardiogram from normal values for the same age and body‐surface areas were calculated. The influences of risk factors were analyzed using univariate and multivariate regression. Lowess curves of time dependence were calculated.

Results

All echocardiographic parameters including ejection fraction (EF) deteriorated significantly over time. Male gender was significantly associated with systolic dilatation of the left ventricle and positively associated with left ventricular mass. Reduction of EF was significantly associated with age at diagnosis and male gender.

Conclusions

Anthracycline doses of <300 mg/m2 may contribute to a decline in cardiac function over time. Although the deterioration in cardiac parameters was not associated with clinical symptoms, life‐long cardiac surveillance for these patients is important to establish the impact of low‐dose anthracycline therapy on long‐term cardiac health. Pediatr Blood Cancer 2010;54:444–448. © 2009 Wiley‐Liss, Inc.
Bronchial hyperreactivity in non‐atopic children with asthma and reflux: Effect of anti‐reflux treatment
Authors: Khoshoo Vikram , Mohnot Sopan , Haydel Robert , Saturno Emilio , Edell Dean , Kobernick Aaron
Published: October 2009

Introduction

The prevalence of bronchial hyperreactivity (BHR) or the effect of anti‐reflux treatment on BHR in children with asthma and gastroesophageal reflux disease (GERD) is not known.

Methods

Thirty non‐atopic children with persistent asthma were studied. Extended esophageal pH monitoring was used to diagnose GERD and methacholine challenge test (MCT) was used as a marker of BHR and performed before and 2 years after anti‐GERD treatment.

Results

Of the 21 patients positive for GERD (group A), 15 had positive MCT suggesting BHR. Of the 9 patients negative for GERD (group B), 5 had positive MCT. On repeat testing 2 years later, 11/15 group A patients and 3/5 group B patients tested negative for BHR. Group A patients were receiving fewer asthma medications and experienced fewer exacerbations than Group B patients.

Conclusions

BHR is prevalent in children with asthma and GERD and improves with anti‐GERD treatment. Pediatr Pulmonol. 2009; 44:1070–1074. ©2009 Wiley‐Liss, Inc.
Non‐tuberculous mycobacteria in children with cystic fibrosis: Isolation, prevalence, and predictors
Authors: Radhakrishnan Dhenuka K. , Yau Yvonne , Corey Mary , Richardson Susan , Chedore Pamela , Jamieson Frances , Dell Sharon D.
Published: October 2009

Background

Screening for non‐tuberculous mycobacteria (NTM) is recommended for adults with cystic fibrosis (CF). The relevance of this organism in North American pediatric CF patients is unclear as there is limited NTM prevalence data for children. We aimed to determine the prevalence of NTM in children with CF from a single expectorated sputum and identify clinical predictors of NTM isolation. Additionally, we compared two different sputum decontamination methods before mycobacterial culture.

Methods

From March to November 2004, all sputum‐producing patients aged 6–18 years attending the CF clinic at the Hospital for Sick Children in Toronto, Canada, were screened for NTM. Sputum samples were processed by both a single (N‐acetyl‐l‐cysteine + NaOH) and double (N‐acetyl‐l‐cysteine + NaOH + oxalic Acid) decontamination method. Using our CF clinic database and patient charts we analyzed differences in FEV1, age, sex, pancreatic sufficiency, body mass index, bacterial colonization, and antibiotic use between NTM positive and negative patients.

Results

Of 98 study patients, 6 (6.1%) were positive for NTM, 2 with Mycobacterium abscessus, and 4 with Mycobacterium avium complex. One patient with M. abscessus had clinically significant lung disease requiring treatment. We found no predictors of NTM isolation. The double decontamination method allowed detection of only half (3/6) of the positive NTM cultures.

Conclusions

As the NTM prevalence rate in children with CF is within the range previously reported in adults and there are no reliable clinical predictors for isolation, annual sputum screening is needed to identify NTM in children. Further research is needed to determine the best sputum decontamination method for NTM culture in pediatric patients. Pediatr Pulmonol. 2009; 44:1100–1106. ©2009 Wiley‐Liss, Inc.
Regulation of proteins mediating neurodegeneration in experimental autoimmune encephalomyelitis and multiple sclerosis
Authors: Jastorff Archana M. , Haegler Katrin , Maccarrone Giuseppina , Holsboer Florian , Weber Frank , Ziemssen Tjalf , Turck Christoph W.
Published: October 2009

Multiple sclerosis is characterized by inflammatory demyelination and axonal loss as pathophysiological correlates of relapsing activity and progressive development of clinical disability. The molecular processes involved in this pathogenesis are still unclear as they are quite complex and heterogeneous. In this article we present protein expression analysis of brain and spinal cord tissues from different models of murine experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for multiple sclerosis. We observed a number of EAE‐specific protein expression and PTM differences. Proteome analysis was extended to multiple sclerosis specimens in order to validate the EAE findings. Our findings suggest the regulation of a number of proteins that shed light on the molecular mechanisms of the disease processes taking place in EAE and multiple sclerosis. We found consistent modulation of proteins including serum amyloid P component, sirtuin 2, dihydropyrimidinase‐related protein family proteins, stathmin 1, creatine kinase B and chloride intracellular channel protein 1. Functional classification of the proteins by database and the literature mining reveals their association with neuronal development and myelinogenesis, suggesting possible disease processes that mediate neurodegeneration.
Quantitative proteomic analysis of ovarian cancer cells identified mitochondrial proteins associated with paclitaxel resistance
Authors: Tian Yuan , Tan Aik‐Choon , Sun Xiaer , Olson Matthew T. , Xie Zhi , Jinawath Natini , Chan Daniel W. , Shih Ie‐Ming , Zhang Zhen , Zhang Hui
Published: October 2009

Paclitaxel has been widely used as an anti‐mitotic agent in chemotherapy for a variety of cancers and adds substantial efficacy as the first‐line chemotherapeutic regimen for ovarian cancers. However, the frequent occurrence of paclitaxel resistance limits its function in long‐term management. Despite abundant clinical and cellular demonstration of paclitaxel resistant tumors, the molecular mechanisms leading to paclitaxel resistance are poorly understood. Using genomic approaches, we have previously identified an association between a BTB/POZ gene, NAC1, and paclitaxel resistance in ovarian cancer. The experiments presented here have applied multiple quantitative proteomic methods to identify protein changes associated with paclitaxel resistance and NAC1 function. The SKOV‐3 ovarian serous carcinoma cell line, which has inducible expression of dominant‐negative NAC1, was used to determine the paclitaxel treatment associated changes in the presence and absence of functional NAC1. Quantitative proteomic analyses were performed using iTRAQ labeling and MS. Two label‐free quantitative proteomic methods: LC‐MS and spectral count were used to increase confidence of proteomic quantification. Candidate proteins related to paclitaxel and NAC1 function were identified in this study. Gene ontology analysis of the protein changes identified upon paclitaxel resistance revealed that cell component enrichment related to mitochondria. Moreover, tubulin and mitochondrial proteins were the major cellular components with changes associated with paclitaxel treatment. This suggests that mitochondria may play a role in paclitaxel resistance.
Temperature dependent 2nd derivative absorbance spectroscopy of aromatic amino acids as a probe of protein dynamics
Authors: Esfandiary Reza , Hunjan Jagtar S. , Lushington Gerald H. , Joshi Sangeeta B. , Middaugh C. Russell
Published: October 2009

Proteins display a broad peak in 250–300 nm region of their UV spectrum containing multiple overlapping bands arising from the aromatic rings of phenylalanine, tyrosine, and tryptophan residues. Employing high resolution 2nd derivative absorbance spectroscopy, these overlapping absorption bands can be highly resolved and therefore provide a very sensitive measure of changes in the local microenvironment of the aromatic side chains. This has traditionally been used to detect both subtle and dramatic (i.e., unfolding) conformational alterations of proteins. Herein, we show that plots of the temperature dependent 2nd derivative peak positions of aromatic residues have measurable slopes before protein unfolding and that these slopes are sensitive to the dielectric properties of the surrounding microenvironment. We further demonstrate that these slopes correlate with hydration of the buried aromatic residues in protein cores and can therefore be used as qualitative probes of protein dynamics.
Design of high‐affinity S100‐target hybrid proteins
Authors: Rezvanpour Atoosa , Phillips Jeremy M. , Shaw Gary S.
Published: October 2009

S100B and S100A10 are dimeric, EF‐hand proteins. S100B undergoes a calcium‐dependant conformational change allowing it to interact with a short contiguous sequence from the actin‐capping protein CapZ (TRTK12). S100A10 does not bind calcium but is able to recruit the N‐terminus of annexin A2 important for membrane fusion events, and to form larger multiprotein complexes such as that with the cation channel proteins TRPV5/6. In this work, we have designed, expressed, purified, and characterized two S100‐target peptide hybrid proteins comprised of S100A10 and S100B linked in tandem to annexin A2 (residues 1–15) and CapZ (TRTK12), respectively. Different protease cleavage sites (tobacco etch virus, PreScission) were incorporated into the linkers of the hybrid proteins. In situ proteolytic cleavage monitored by 1H‐15N HSQC spectra showed the linker did not perturb the structures of the S100A10‐annexin A2 or S100B‐TRTK12 complexes. Furthermore, the analysis of the chemical shift assignments (1H, 15N, and 13C) showed that residues T102‐S108 of annexin A2 formed a well‐defined α‐helix in the S100A10 hybrid while the TRTK12 region was unstructured at the N‐terminus with a single turn of α‐helix from D108‐K111 in the S100B hybrid protein. The two S100 hybrid proteins provide a simple yet extremely efficient method for obtaining high yields of intact S100 target peptides. Since cleavage of the S100 hybrid protein is not necessary for structural characterization, this approach may be useful as a scaffold for larger S100 complexes.
Development of algorithms for predicting ignition probabilities and explosion frequencies
Authors: Moosemiller Mike
Published: October 2009

This article covers the development of algorithms for predicting the frequencies of explosions based on a variety of design, operating and environmental conditions. Algorithms were developed for estimating unit‐based explosion frequencies, such as those reported in API, but in more detail and covering a much broader range of chemical process types. This article also shows the developed methods for predicting scenario‐based explosion frequencies, using frequencies of initiating events and conditional probabilities of immediate ignition and delayed ignition resulting in explosion. The algorithms were based on a combination of published data and expert opinion. © 2009 American Institute of Chemical Engineers Process Saf Prog, 2010
Photophysical properties of the asymmetrically substituted spirobifluorenes spiro‐DPO and spiro‐MeO‐DPO
Authors: Brendel Cornelia M. , Dias Fernando B. , Saragi Tobat P. I. , Monkman Andy P. , Salbeck Josef
Published: October 2009

The photophysical behaviour of the oxadiazolyl (PBD) and diphenylamino (TAD) substituted spirobifluorenes 2′,7′‐bis‐(N,N‐diphenylamino)‐2‐(5‐(4‐tert‐butylphenyl)‐1,3,4‐oxadiazol‐2‐yl)‐9,9′‐spirobifluoren (spiro‐DPO) and 2′,7′‐bis‐(N,N‐diphenylamino)‐2‐(5‐(4‐tert‐butylphenyl)‐1,3,4‐oxadiazol‐2‐yl)‐9,9′‐spirobifluoren (spiro‐MeO‐DPO) has been investigated by temperature‐dependent steady‐state absorption and luminescence spectroscopy and gated measurements. Fluorescence and phosphorescence lifetime measurements, relative quantum yields and dipole moments of the excited states have been determined. Asymmetrically substituted spirobifluorenes exhibit charge‐transfer (CT) emission due to coupling (spiroconjugation) between the fluorene fragments of spirobifluorene. They show a considerable ground‐state dipole moment and exist as equilibrating conformeres. Population of the CT state only occurs after absorption to the locally excited singlet state. The CT fluorescence is dominated by the emission of two equilibrating conformeres with similar dipole moments. At low temperature they planarize in both molecular halves and show strong phosphorescence that is still detectable at room temperature.
The effect of rapid thermal annealing on characteristics of carbon coatings on optical fibers
Authors: Yu Jen‐Feng , Chen Tsuen‐Sung , Lin Hung‐Chien , Shiue Sham‐Tsong
Published: October 2009

Carbon films are deposited on silica glass fibers by radio‐frequency plasma‐enhanced chemical vapor deposition (rf‐PECVD), and the properties of these optical fibers are improved by rapid thermal annealing. The annealing temperatures are set to 100, 200, 300, 400, 500, 550, 600, and 700 °C. Experimental results show that the thickness and surface roughness of carbon films decrease with increasing annealing temperature, ranging from as‐deposited to 500 °C, while the sp2 carbon bonding, sp3 CH3 bonding, optical bandgap, and water contact angle (CA) of carbon films increase. As the annealing temperature increases from 550 to 700 °C, parts of the carbon films are delaminated. The sp3 CH3 bonding in carbon films is shifted to the sp3 CH2 bonding, and the sp3 CH2 bonding is subsequently transferred to the sp2 CH bonding. Meanwhile, the amount of the sp2 carbon bonding in carbon films increases, while the optical bandgap decreases. Based on the evaluation of water repellency and low‐temperature morphology of carbon films, the carbon film annealed at a temperature of 500 °C is the best for production of carbon‐coated optical fibers. As compared to conventional thermal annealing (CTA), rapid thermal annealing (RTA) is more effective to improve the properties of carbon‐coated optical fibers.
Effect of lattice mismatch on gate lag in high quality InAlN/AlN/GaN HFET structures
Authors: Leach J. H. , Wu M. , Ni X. , Li X. , Özgür Ü. , Morkoç H.
Published: October 2009

Grown lattice matched to GaN, InAlN‐based heterojunction field effect transistors (HFETs) are promising due to the relatively large band discontinuity at the interface and lack of misfit strain. Despite the recent progress in the growth, there still exists some questions as to the true lattice matching condition of InAlN to GaN due to discrepancies in the value of the lattice parameters of the InN binary, as well as the literature value of the InAlN bowing parameters. In order to address this, we used the gate lag as a supplementary measurement to verify lattice matching to the underlying GaN, as strain‐free layers would not have piezoelectric charge at the surface, which would be one source of lag. We observe very low lag for a nearly lattice matched barrier, and a marked increase as the composition deviates from the lattice matched condition. Additionally, FETs fabricated on a nearly matched layer boast a maximum drain current of over 1.5 and ∼2.0 A/mm and transconductances of ∼275 and ∼300 mS/mm at DC and in pulsed modes, respectively, and a cutoff frequency of 15.9 GHz (an fT*LG product of 10.3) for a gate length of 0.65 µm.
Resistivity study of RuSr2GdCu2O8 superconductor
Authors: Mohan Rajneesh , Singh Kiran , Kaur Nupinderjeet , Kumar Naresh , Bhattacharya Shovit , Gaur Neeraj K. , Gupta Shiv K. , Singh Ram K.
Published: October 2009

The superconducting properties of RuSr2GdCu2O8 (Ru‐1212) superconductor strongly depend on the processing conditions. In this report we have made an investigation on the influence of processing method and heat treatments on the superconducting properties, as well as normal state resistivity of RuSr2GdCu2O8 (Ru‐1212) compound. The samples were prepared using solid‐state reaction of high purity oxides and carbonates of constituents cations through direct method, precursor method, and standard method used for the synthesis of Ru‐1212 compounds. These samples were then subjected to different annealing treatments in different atmosphere (oxygen and air) for 120 h. They have been investigated by X‐ray diffraction, dc resistivity and scanning electron microscopy. The normal state resistivity has been studied on the basis of various conduction mechanisms.
Slow positron moderator studies at Brandeis – Collaborative work with Karl F. Canter
Authors: Amarendra G.
Published: October 2009

The collaborative research work carried out with Karl F Canter on slow positron moderators at Brandeis University is presented. A compact electrostatic positron beam has been designed and constructed for the determination of slow positron yield of single crystalline W(100) moderator foil with provision for in‐situ heating and surface characterization. Moderation yield is found to gradually increase with successive heating cycles, which is also correlated with the removal of surface and bulk carbon‐vacancy complexes. The work on inert Ar gas moderator is also briefly discussed. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Pharmacodynamic interaction of captopril with garlic in isoproterenol‐induced myocardial damage in rat
Authors: Asdaq Syed Mohammed Basheeruddin , Inamdar Mohammed Naseeruddin
Published: October 2009

It is known that various preparations of garlic and angiotensin‐converting enzyme (ACE) inhibitor such as captopril (CAP) have beneficial effects on the left ventricular function and cardiovascular events after myocardial infarction (MI) when used individually. There is no reported interaction between garlic homogenate (GH) and CAP during and after acute MI. Thus the purpose of the current study was to evaluate the possible pharmacodynamic interaction of GH with CAP on isoproterenol (ISO)‐induced myocardial damage in rat. Female Wistar albino rats were treated with GH at three different doses of 125; 250 and 500 mg/kg orally for 30 days and CAP (30 mg/kg,p.o.) was incorporated in the interactive groups during the last seven days of GH treatment. Myocardial damage was induced by administration of ISO (150 mg/kg,s.c.) for two consecutive days. Biochemical parameters were studied in serum and heart tissue homogenate of all animals. The GH 250 mg/kg was found to dislodge the effect of ISO on superoxide dismutase and catalase and retained the activities of LDH and CK‐MB. Incorporation of CAP during GH treatment provided further protection to myocardium from injury. However, higher dose of GH alone or with CAP failed to prevent damaging effect of ISO. Histopathological determinations confirmed biochemical findings. Thus it is concluded that the combination needs to be used carefully when garlic is consumed at high doses. Copyright © 2009 John Wiley & Sons, Ltd.
Prequential analysis of complex data with adaptive model reselection
Authors: Clarke Jennifer , Clarke Bertrand
Published: October 2009

In Prequential analysis, an inference method is viewed as a forecasting system, and the quality of the inference method is based on the quality of its predictions. This is an alternative approach to more traditional statistical methods that focus on the inference of parameters of the data generating distribution. In this paper, we introduce adaptive combined average predictors (ACAPs) for the Prequential analysis of complex data. That is, we use convex combinations of two different model averages to form a predictor at each time step in a sequence. A novel feature of our strategy is that the models in each average are re‐chosen adaptively at each time step. To assess the complexity of a given data set, we introduce measures of data complexity for continuous response data. We validate our measures in several simulated contexts prior to using them in real data examples. The performance of ACAPs is compared with the performances of predictors based on stacking or likelihood weighted averaging in several model classes and in both simulated and real data sets. Our results suggest that ACAPs achieve a better trade off between model list bias and model list variability in cases where the data is very complex. This implies that the choices of model class and averaging method should be guided by a concept of complexity matching, i.e. the analysis of a complex data set may require a more complex model class and averaging strategy than the analysis of a simpler data set. We propose that complexity matching is akin to a bias‐variance tradeoff in statistical modeling. Copyright © 2009 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 2: 000‐000, 2009
A robust method for comparing two treatments in a confirmatory clinical trial via multivariate time‐to‐event methods that jointly incorporate information from longitudinal and time‐to‐event data
Authors: Saville Benjamin R. , Herring Amy H. , Koch Gary G.
Published: October 2009

We consider regulatory clinical trials that require a prespecified method for the comparison of two treatments for chronic diseases (e.g. Chronic Obstructive Pulmonary Disease) in which patients suffer deterioration in a longitudinal process until death occurs. We define a composite endpoint structure that encompasses both the longitudinal data for deterioration and the time‐to‐event data for death, and use multivariate time‐to‐event methods to assess treatment differences on both data structures simultaneously, without a need for parametric assumptions or modeling. Our method is straightforward to implement, and simulations show that the method has robust power in situations in which incomplete data could lead to lower than expected power for either the longitudinal or survival data. We illustrate the method on data from a study of chronic lung disease. Copyright © 2009 John Wiley & Sons, Ltd.
Mathematics, critical literacy, and youth participatory action research
Authors: Yang K. Wayne
Published: October 2009

This article examines mathematics education as both the site and object of transformation for a youth PAR project in which students researched and evaluated their urban high school in Oakland, California. These youth researchers were trained as part of a sociology course as well as a mathematics class designed to both remediate gaps in math preparation and accelerate students into higher‐order math literacy. This study differs from and extends other studies that describe mathematics as a tool for social critique. It considers youth research in and through mathematics as a more ideologically open endeavor in that youth do not simply reproduce predetermined criticisms of social inequality. Thus, this project translates extensive work in critical literacy, new media literacy, and youth participatory action research to a mathematics context.
The Thermochemical Behaviour of Te8O10(PO4)4 and its Use for Phosphide Telluride Synthesis
Authors: Schmidt Peer , Dallmann Hannelore , Kadner Gudrun , Krug Jutta , Philipp Frauke , Teske Klaus
Published: October 2009

The tellurium oxide phosphate Te8O10(PO4)4 was synthesised by thermal decomposition of Te2O3HPO4 at temperatures above 400 °C. Te8O10(PO4)4 melts at 570 °C and evaporates at 820 °C. The thermodynamic standard data were determined by solution calorimetry and differential scanning calorimetry and were optimised by thermodynamic modelling of the binary system TeO2/P2O5: ΔH{}^0_298[Te8O10(PO4)4] =–5844(2) kJ·mol–1; S{}^0_298[Te8O10(PO4)4] = 823.3 J·mol–1·K–1. The phase relations in quaternary systems M/P/Te/O (M = Ti, Zr, Ce) were calculated and optimised synthesis parameters for phosphide tellurides were derived.
Darstellung, Kristall‐ und Molekülstruktur eines zwölfgliedrigen N,N′‐Di‐Lithium‐cyclosiloxazans [Me2SiOSiMe2N(Li)SiMe2O]2
Authors: Veith Michael , Rammo Andreas , Heim Ralf , Huch Volker
Published: October 2009

The twelve membered and eighteen membered cyclosiloxazanes [Me2SiOSiMe2N(H)SiMe2O]2 (3) and [Me2SiOSiMe2N(H)SiMe2O]3 (4) have been obtained as colourless liquids from the reaction of 1,5‐Dichlorohexamethyltrisiloxane with ammonia at–50 °C without any solvent. For compound 3 and 4, the yield is 30 % and 43 %, respectively. The treatment of 3 with two equivalents of n‐butyllithium in n‐hexane leads in almost quantitative yield (93 %) to the dilithiumsilylamide [Me2SiOSiMe2N(Li)SiMe2O]2 (5). Compound 5 can be isolated at room temperature and recrystallized from benzene without any decomposition or contraction of the ring size. An X‐ray structure determination on [Me2SiOSiMe2N(Li)SiMe2O]2 (5) reveals a waved crown‐like twelve membered Si6N2O4‐cycle. Each of the two lithium ions is coordinated by two nitrogen and two oxygen atoms leading to a square pyramid, in which the metal occupies the apex. The two square‐pyramidal coordination figures are located above and below the waved crown‐like Si6N2O4‐ring sharing a common edge by the atoms N(1) and N(2). All synthesised compounds have been characterised by spectroscopic methods. Because of the lower solubility of the dilithiumsilylamide 5, only a 1H‐NMR could be applied for further characterisation in solution.
Hydroxocobalamin dose escalation improves metabolic control in cblC
Authors: Carrillo‐Carrasco N. , Sloan J. , Valle D. , Hamosh A. , Venditti C. P.
Published: October 2009

Cobalamin C (cblC), a combined form of methylmalonic acidaemia and hyperhomocysteinaemia, is recognized as the most frequent inborn error of intracellular cobalamin metabolism. This condition can be detected by expanded newborn screening and can have an acute neonatal presentation that is life‐threatening if not suspected and promptly treated. Intramuscular (IM) hydroxocobalamin (OHCbl) is the main treatment for patients with cblC, but formal dosing guidelines do not exist. A clinical improvement and a decrease of plasma methylmalonic acid (MMA) and total homocysteine (tHcy) levels, and an increase in methionine are typically observed after its initiation. It is well recognized that despite treatment, long‐term complications such as developmental delay and progressive visual loss, may still develop. We describe the biochemical response of a 13‐year‐old boy with worsening metabolic parameters despite strict adherence to a conventional treatment regimen. We progressively increased the OHCbl dose from 1 to 20 mg IM per day and observed a dose‐dependent response with an 80% reduction of plasma MMA (25 to 5.14 μmol/L; normal range <0.27 μmol/L), a 55% reduction of tHcy (112 to 50 μmol/L; normal range: 0–13 μmol/L) and a greater than twofold increase in methionine (17 to 36 μmol/L; normal range: 7–47 μmol/L). This suggests that higher OHCbl doses might be required to achieve an optimal biochemical response in cblC patients, but it is unknown whether it may slow or eliminate other complications. Future clinical trials to determine the benefits of higher‐dose OHCbl therapy in patients with cblC and other disorders of intracellular cobalamin metabolism should be planned.
Clinical and biochemical studies in mucopolysaccharidosis type II carriers
Authors: Schwartz I. V. D. , Pinto L. L. C. , Breda G. , Lima L. , Ribeiro M. G. , Mota J. G. , Acosta A. X. , Correia P. , Horovitz D. D. G. , Porciuncula C. G. G. , Lipinski‐Figueiredo E. , Fett‐Conte A. C. , Oliveira Sobrinho R. P. , Norato D. Y. J. , Paula A. C. , Kim C. A. , Duarte A. R. , Boy R. , Leistner‐Segal S. , Burin M. G. , Giugliani R.
Published: October 2009

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty‐two women at risk to be a carrier, with a mean age of 34.1 years (range 16–57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non‐carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non‐carriers; there was, however, an overlap between carriers’ and non‐carriers’ values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.
Cognitive and social profiles in two patients with cobalamin C disease
Authors: Beauchamp M. H. , Anderson V. , Boneh A.
Published: October 2009

Cobalamin C (cblC) disease, an inborn error of vitamin B12 metabolism, results in neurometabolic, neurochemical and neuroanatomical changes. Little is known of the long‐term effects of the disorder on cognition and behaviour in children. Here, the complete neuropsychological profiles of two 12‐year‐old girls with cblC disease are presented. The two girls were tested longitudinally with standardized neuropsychological tests including intellectual ability, attention and memory, as well as executive, adaptive and behavioural function. The results indicate the presence of intellectual dysfunction, attention problems, and concerns with behavioural aspects of executive function. Both patients demonstrated a pattern of decreasing intellectual function over time, which may reflect a growing developmental gap in comparison with their same age peers. These impairments are in contrast to the relatively spared verbal expression and comprehension abilities, as well as strengths in sociability. The findings highlight a pattern of neuropsychological strengths and weaknesses that may distinguish cblC disease from other inborn errors of metabolism. Overt sociability such as observed in these two patients may actually mask underlying cognitive deficits because the patients appear to function at a more advanced level than that reflected by quantitative assessment of intellectual and cognitive functioning. This is of clinical and functional importance and suggests that accurate determination of cognitive, adaptive and social abilities necessitates an in‐depth and broad evaluation. The presence of significant intellectual and cognitive deficits also underscores the need to document and monitor cognitive development in children with cblC disease and to consider remediative and adaptive learning strategies.
Romantic relationships and delinquent behaviour in adolescence: The moderating role of delinquency propensity
Authors: Eklund Jenny M. , Kerr Margaret , Stattin Håkan
Published: October 2009

There is some evidence that adolescent romantic involvement is associated with delinquent behaviour. One aim of this longitudinal study was to determine whether this holds for romantic relationships deemed important by the participants. A second aim was to test whether this association was stronger for adolescents with pre‐existing delinquent behaviour and personality traits of impulsivity and thrill seeking (delinquency propensity). Sex differences also were examined. Participants were 686 7th and 8th grade students who completed three assessments over three years. The results showed that delinquency was associated with earlier romantic relationships among those who were higher in delinquency propensity one year earlier. This association was stronger among girls than boys. Thus, romantic relationships amplified girls' and boys' existing delinquency propensity, but this was strongest among girls.
Glutamine attenuates acute lung injury by inhibition of high mobility group box protein-1 expression during sepsis
Authors: Kwon Woon Yong , Suh Gil Joon , Kim Kyung Su , Jo You Hwan , Lee Jae Hyuk , Kim Kyuseok , Jung Sung Koo
Published: October 2009

Heat shock protein 70 (HSP70) is reported as the main factor responsible for the beneficial effects of glutamine (GLN) and as a negative regulator of high mobility group box protein-1 (HMGB-1) expression. Our aim was to determine whether GLN attenuates acute lung injury (ALI) by the inhibition of HMGB-1 expression during sepsis. Male Sprague–Dawley rats were subjected to caecal ligation and puncture (CLP) to induce sepsis. GLN or saline was administered through tail vein 1 h after CLP. Then, quercetin (Q), an inhibitor of HSP70, was utilised to assess the role of the enhanced HSP70. We observed the survival of the subjects. At 24 h post-CLP, we measured lung HSP70, phosphorylated heat shock factor-1 (HSF-1-p) and HMGB-1 expressions, NF-κB DNA-binding activity and ALI occurrence. We also measured serum HSP70, IL-6 and HMGB-1 concentrations. GLN improved survival during sepsis. In GLN-treated rats, lung HSP70 and HSF-1-p expressions were enhanced, lung HMGB-1 expression and NF-κB DNA-binding activity were suppressed, and ALI was attenuated. Furthermore, in GLN-administered rats, serum HSP70 concentration was higher, and serum IL-6 and HMGB-1 concentrations were lower than those in non-treated rats. Q inhibited the enhancement of HSP70 and HSF-1-p expressions and abrogated the GLN-mediated benefits. In conclusion, GLN attenuated ALI and improved survival by the inhibition of HMGB-1 expression during sepsis in rats. These benefits were associated with the enhancement of HSP70 expression by GLN.
A vernalization-intensity model to predict bolting in sugar beet
Authors: MILFORD G. F. J. , JARVIS P. J. , WALTERS C.
Published: October 2009

A new model is presented that relates the numbers of bolters in sugar-beet crops to an intensity of vernalization calculated as the accumulated number of hours between sowing and the end of June that temperatures were between 0 and 13°C, with each temperature within this range differentially weighted for its vernalizing effect. The model allows varieties to be characterized in terms of a threshold number of vernalizing hours needed to induce bolting (the vernalization requirement) and the increase in the proportion of bolted plants with each additional 10 vernalizing hours accumulated above this vernalizing threshold (the bolting sensitivity). When parameterized for variety, the model allows the level of bolting to be predicted for crops sown on specific dates in particular locations.

Data from variety-assessment trials done at a wide range of locations throughout the main UK sugar-beet growing areas between 1973 and 2006, and from early sown bolting trials done at a few sites between 2000 and 2008, were used to define specific aspects of the model. These included the range and weightings of vernalizing temperatures, the period during which vernalization occurs, and the temperatures likely to cause plants to become devernalized.

The vernalization-intensity bolting model was parameterized and validated using separate subsets of the UK variety-assessment trial data. It was shown to be more discriminating and robust than an existing ‘cool-day’ model, which relates bolting to the number of days from sowing in which the maximum air temperature was below 12°C. Examples are given of the use of the new model to assess the bolting risk associated with early sowing in different regions of the UK, to interpret recent patterns of bolting (especially the large numbers of bolters seen in some commercial crops in 2008), and its potential use as an advisory tool.
Particle dispersion by random waves in rotating shallow water
Authors: BÜHLER OLIVER , HOLMES-CERFON MIRANDA
Published: October 2009

We present a theoretical and numerical study of wave-induced particle dispersion due to random waves in the rotating shallow-water system, as part of an ongoing study of particle dispersion in the ocean. Specifically, the effective particle diffusivities in the sense of Taylor (Proc. Lond. Math. Soc., vol. 20, 1921, p. 196) are computed for a small-amplitude wave field modelled as a stationary homogeneous isotropic Gaussian random field whose frequency spectrum is bounded away from zero. In this case, the leading-order diffusivity depends crucially on the nonlinear, second-order corrections to the linear velocity field, which can be computed using the methods of wave–mean interaction theory. A closed-form analytic expression for the effective diffusivity is derived and carefully tested against numerical Monte Carlo simulations. The main conclusions are that Coriolis forces in shallow water invariably decrease the effective particle diffusivity and that there is a peculiar choking effect for the second-order particle flow in the limit of strong rotation.
Superficial temporal artery pseudoaneurysm: first reported case after parotid surgery
Authors: Bernstein J M , Bury R W , Nigam A
Published: October 2009

Objective:

To describe a case of superficial temporal artery pseudoaneurysm occurring as a rare complication of parotid surgery (to the authors' knowledge, the first such case reported), to review the aetiology of superficial temporal artery pseudoaneurysm, and to highlight pseudoaneurysm as a cause of facial swelling after parotidectomy.

Method:

A literature search of the PubMed and EMBASE databases was carried out using the Medical Subject Heading key words ‘superficial temporal artery’, ‘aneurysm’, ‘pseudoaneurysm’ and ‘parotid’.

Result:

No previously reported cases of superficial temporal artery aneurysm or pseudoaneurysm following parotid surgery were identified.

Conclusion:

Pseudoaneurysm of the superficial temporal artery is a rare complication of parotid surgery which has not previously been reported.
Brain-based sex differences in parenting propagate emotion expression
Authors: Swain James E.
Published: October 2009

Parent-infant emotional expressions vary according to parent and infant gender. Such parent-infant interactions critically affect infant development. Neuroimaging research is exploring emotion-related brain function that varies according to gender, and regulates parenting thoughts and behaviors in the early postpartum. Through specific brain functions, parenting serves to program the infant brain for the next generation of sex-specific emotional expression.
Human female exogamy is supported by cross-species comparisons: Cause to recognise sex differences in societal policy?
Authors: Madison Guy
Published: October 2009

A sex difference in the tendency to outbreed (female exogamy) is a premise for the target article's proposed framework, which receives some support by being shared with chimpanzees but not with more distantly related primates. Further empirical support is provided, and it is suggested that recognition of sex differences might improve effective fairness, taking sexual assault as a case in point.
Reciprocity of laughing, humor, and tickling, but not tearing and crying, in the sexual marketplace
Authors: Provine Robert R.
Published: October 2009

Laughing, humor, and tickling, but not tearing and crying, involve the give-and-take that provides value and a basis for exchange in the psychosexual marketplace.
Technology Assessment of Periodic Health Examinations for School Children in Japan
Authors: Hisashige Akinori
Published: October 2009

In Japan, preventive health services have been heavily concentrated in mass screening. This prioritization is also true in the field of school health. Annual mass health screenings have been provided to 21.3 million children from kindergarten to university level under the School Health Law. In 1973, periodic health examinations were extended to include screenings for renal and heart diseases. This extensive screening program has been introduced without any evidence supporting its effectiveness. Although available data relative to these screenings in Japan were examined, neither the efficacy of the tests nor the effectiveness of the screenings were observed. Moreover, costs for the tests during the initial phase amounted to US $120 million and $65 million, respectively.
The Technology Assessment and Practice Guidelines Forum: A Modified Group Judgment Method
Authors: Perry Seymour , Wilkinson Susann L.
Published: October 2009

This article describes a new group-judgment process, modified from the consensus development approach of the U.S. National Institutes of Health. It is called the “forum” method, a shorthand term for “technology assessment and practice guidelines forum.” This approach is aimed at (a) describing the current state of knowledge of the technology under study; (b) developing practice guidelines for the use of the technology; and (c) providing information for insurers, consumers, policymakers, and others. A pilot study was conducted focusing on total parenteral nutrition. The validity of the process and of the recommendations and their acceptability were evaluated in a survey of participants and a selected group of nonparticipants. Based on the survey results, the forum method appears to be a valuable method for assessing technologies, defining their clinical role, and developing practice guidelines.
Lower Back Pain: Laminectomies, Spinal Fusions, Demographics, and Socioeconomics
Authors: Bentkover Judith D. , Sheshinski Ruth H. , Hedley-Whyte John , Warfield Carol A. , Mosteller Frederick
Published: October 2009

The models and analyses used in this study represent an important step in the continued search for the optimum use of surgery for the treatment of lower back pain. The likelihood of patients who are hospitalized with lower back pain in Massachusetts receiving either laminectomies or spinal fusions or both was increased when any of the following demographic, socioeconomic, or medical characteristics were present: white, male, well insured, young, routine admission, admitted to a medium-sized hospital, admitted to a teaching hospital, admitted to a hospital with a high occupancy rate, and discharged home.
Progress on Firms Research
Authors: Neuhauser Duncan
Published: October 2009

Firms research combines parallel providers of care, ongoing patient randomization, and continuous experimental changes and improvement. This form of efficient research now has a substantial track record of published studies by a growing number of hospitals.
The Intensive Care Unit: The Unfolding and Ambiguities of Survival Therapy
Authors: Reiser Stanley Joel
Published: October 2009

The intensive care unit (ICU), one of the great achievements of modern medicine, is both a set of technologies and a space with a special function. This essay traces the evolution of the ICU's crucial technologies, and how the space bearing this name was carved out in the hospital. Ethical, legal, and social developments, an important part of this story, are incorporated in it.
Neonatal Intensive Care: When and Where Is It Justified?
Authors: Svenningsen Nils W.
Published: October 2009

There is a wide panorama of disorders in the newborn infant where neonatal intensive care has been proven effective in reducing mortality. Although modern neonatal intensive care can be very costly, shortand simple interventions for support and resuscitation still can be highly beneficial. In reviewing the field of neonatal intensive careduring the 1980s, it becomes evident that a major challenge for the future will be to apply physiological principles of great and provenvaluefor the newborn baby to more simple devices. Only thereby canthe technology of neonatal care defined as a complex of actions–not only equipment and techniques–become justified for future generations.
Volume and Outcome of Organ Transplantation
Authors: Banta H. David , Engel Gerard L. , Scherstén Tore
Published: October 2009

In general, technically demanding medical procedures are associated with better outcomes when they are carried out in institutions and by physicians with higher volumes of practice. This paper examines the evidence for a volume–outcome relationship in the case of organ transplantation. Although few studies have been done on this subject, existing evidence is consistent with improved outcomes at higher volumes. Therefore, evidence supports policies that regionalize transplantation services.
A Methodology for Simulating the Impact of DNA-probe Services on the Outcomes of Pregnancies
Authors: Beech Roger , Rona Roberto J. , Swan Anthony V. , Wilson Oonagh M. , Mandalia Sundhiya
Published: October 2009

For certain single-gene disorders, DNA probes allow individuals to make more informed decisions about family size and the outcomes of pregnancies. They may also have important psychological effects. We present a method of assessing their impact on the outcomes of pregnancy. We conclude that the traditional approach, which focuses solely on the potential of prenatal diagnostic services to reduce affected births, is limited. It neglects the potential of such services to promote an increase in unaffected births by reducing the number of unnecessary terminations.
The Desired Field-Performance Characteristics of New Improved Vaccines for the Developing World
Authors: de Quadros Ciro A. , Carrasco Peter , Olivé Jean-Marc
Published: October 2009

Although the vaccination initiatives undertaken during the past decade are the cornerstones for protecting the world's children and helping to ensure their survival and development, the vaccines currently being employed may become obstacles for further disease reduction or eradication. Their characteristics complicate or increase the burden on health care infrastructures to maintain or expand vaccine delivery systems. This paper examines an experience with the vaccine technologies that currently are being used by immunization programs in developing countries, illustrating the field problems and obstacles associated with their use. It discusses the advantages and benefits that would accrue if new or improved, heat-stable, multi-antigen vaccines that require only one or two, preferably oral, doses were to become available.
Maternal Immunization to Prevent Infectious Diseases in the Neonate or Infant
Authors: Insel Richard A. , Amstey Marvin , Woodin Kathleen , Pichichero Michael
Published: October 2009

The approach of providing passive protection to young infants by immunizing pregnant women can bypass the problems of immunological immaturity in the neonate, avoid or delay active immunization of the infant in the first year of life, and prevent transmission of an infection from the mother to the neonate. Optimal vaccines for this approach should induce high immunoglobulin G antibody titers that quickly reach their maximum level after immunization and persist at protective levels for several years, thus providing passive protection in subsequent pregnancies. Specific applications of this approach include the worldwide practice of maternal immunization with tetanus toxoid vaccine and ongoing studies of maternal immunization to preventHaemophilus influenzaetype b, group B strepto-coccal, pneumococcal, meningococcal, and human immunodeficiency virus infection in the infant. Addressing the cultural, sociological, and legal aspects of maternal immunization will be required to ensure the success of this approach.