bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic administration of prothrombin complex concentrates for congenital prothrombin deficiency with a novel frameshift mutation, prothrombin saitama
Authors: Seki Masafumi , Koh Katsuyoshi , Inoue Takeshi , Tomita Yuzo , Kato Motohiro , Shimizu Masaki , Morishita Eriko , Hanada Ryoji
Published: November 2012

Prothrombin (Factor II, FII) deficiency is an extremely rare autosomal recessive condition with an estimated incidence of 1:2 million. As severe and life‐threatening bleeding is rare in FII deficiency, on demand therapy with administration of prothrombin complex concentrates (PCCs) or fresh frozen plasma is generally performed, and prophylactic therapy for FII deficiency has been reported in only three cases. Thus, its optimal dosage and schedule has remained uncertain. Here we report a case of severe prothrombin deficiency with a novel frameshift mutation of the F2 gene, who was started on prophylactic administration. Pediatr Blood Cancer 2013; 60: 503–505. © 2012 Wiley Periodicals, Inc.
Quantitative and qualitative 2D electrophoretic analysis of differentially expressed mitochondrial proteins from five mouse organs
Authors: Techritz Sandra , Lützkendorf Susanne , Bazant Esther , Becker Silke , Klose Joachim , Schuelke Markus
Published: November 2012

Mitochondria fulfill many tissue‐specific functions in cell metabolism. We set out to identify differences in the protein composition of mitochondria from five tissues frequently affected by mitochondrial disorders. The proteome of highly purified mitochondria from five mouse organs was separated by high‐resolution 2DE. Tissue‐specific spots were identified through nano‐LC/ESI‐MS/MS and quantified by densitometry in ten biological replicates. We identified 87 consistently deviating spots representing 48 proteins. The percentage of variant spots ranged between 4.2% and 6.0%; 21 proteins having tissue‐specific isospots. Consistent tissue‐specific processing/regulation was seen for carbamoyl‐phosphate‐synthase, aldehyde‐dehydrogenase 2, ATP‐synthase α‐chain, and isocitrate‐dehydrogenase α‐subunit. Thirty tissue‐specific proteins were associated with mitochondrial disorders in humans. We further identified alcohol‐dehydrogenase, catalase, quinone‐oxidoreductase, cyclophilin‐A, and Upf0317, a potential biotin‐carboxyl‐carrier protein, which had not been annotated as “mitochondrial” in Gene Ontology or MitoCarta databases. Their targeting to the mitochondria was verified by transfection of full‐length GFP‐tagged plasmids. Given the high evolutionary conservation of mitochondrial metabolic pathways, these data further annotate the mitochondrial proteome and advance our understanding of the pathophysiology and tissue‐specificity of symptoms seen in patients with mitochondrial disorders. The generation of 2D electrophoretic maps of the mitochondrial proteome using tissue specimens in the milligram range facilitates this technique for clinical applications and biomarker research.
SILAC‐based quantitative proteomic analysis of gastric cancer secretome
Authors: Marimuthu Arivusudar , Subbannayya Yashwanth , Sahasrabuddhe Nandini A. , Balakrishnan Lavanya , Syed Nazia , Sekhar Nirujogi Raja , Katte Teesta V. , Pinto Sneha M. , Srikanth Srinivas M. , Kumar Praveen , Pawar Harsh , Kashyap Manoj K. , Maharudraiah Jagadeesha , Ashktorab Hassan , Smoot Duane T. , Ramaswamy Girija , Kumar Rekha V. , Cheng Yulan , Meltzer Stephen J. , Roa Juan Carlos , Chaerkady Raghothama , Prasad T. S. Keshava , Harsha H. C. , Chatterjee Aditi , Pandey Akhilesh
Published: November 2012

Purpose

Gastric cancer is a commonly occurring cancer in Asia and one of the leading causes of cancer deaths. However, there is no reliable blood‐based screening test for this cancer. Identifying proteins secreted from tumor cells could lead to the discovery of clinically useful biomarkers for early detection of gastric cancer.

Experimental design

A SILAC‐based quantitative proteomic approach was employed to identify secreted proteins that were differentially expressed between neoplastic and non‐neoplastic gastric epithelial cells. Proteins from the secretome were subjected to SDS‐PAGE and SCX‐based fractionation, followed by mass spectrometric analysis on an LTQ‐Orbitrap Velos mass spectrometer. Immunohistochemical labeling was employed to validate a subset of candidates using tissue microarrays.

Results

We identified 2205 proteins in the gastric cancer secretome of which 263 proteins were overexpressed greater than fourfold in gastric cancer‐derived cell lines as compared to non‐neoplastic gastric epithelial cells. Three candidate proteins, proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin mannose binding 2 (LMAN2), and PDGFA‐associated protein 1 (PDAP1) were validated by immunohistochemical labeling.

Conclusions and clinical relevance

We report here the largest cancer secretome described to date. The novel biomarkers identified in the current study are excellent candidates for further testing as early detection biomarkers for gastric adenocarcinoma.
Electron–phonon coupling in the two‐dimensional electron gas on Bi2Se3
Authors: Barreto Lucas , Bianchi Marco , Guan Dandan , Hatch Richard , Mi Jianli , Iversen Bo Brummerstedt , Hofmann Philip
Published: November 2012

magnified image

The electron–phonon coupling in the Rashba‐split two‐dimensional electron gas near the surface of the topological insulator Bi2Se3 is studied by temperature‐dependent angleresolved photoemission. The coupling strength is found to be rather weak, with an electron–phonon mass enhancement parameter $ \lambda = 0.12(8). $ (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hydrogen isotope effects on covalent and noncovalent interactions: The case of protonated rare gas clusters
Authors: Moncada Félix , Uribe Lalita S. , Romero Jonathan , Reyes Andrés
Published: November 2012

We investigate hydrogen isotope and nuclear quantum effects on geometries and binding energies of small protonated rare gas clusters (Rg
$_n$X
$^ +$, Rg = He,Ne,Ar, X = H,D,T, and
$n$ = 1–3) with the any particle molecular orbital (APMO) MP2 level of theory (APMO/MP2). To gain insight on the impact of nuclear quantum effects on the different interactions present in the Rg
$_n$X
$^ +$ systems, we propose an APMO/MP2 energy decomposition analysis scheme. For RgH
$^ +$ ions, isotopic substitution leads to an increase in the stability of the complex, because polarization and charge transfer contributions increase with the mass of the hydrogen. In the case of Rg
$_2$H
$^ +$ complexes, isotopic substitution results in a shortening and weakening of the rare gas‐hydrogen ion bond. For Rg
$_3$X
$^ +$ complexes, the isotope effects on the rare gas binding energy are almost negligible. Nevertheless, our results reveal that subtle changes in the charge distribution of the Rg
$_2$X
$^ +$ core induced by an isotopic substitution have an impact on the geometry of the Rg
$_3$X
$^ +$ complex. © 2012 Wiley Periodicals, Inc.
Curracurrong: a stream programming environment for wireless sensor networks
Authors: Kakkad Vasvi , Attar Saeed , Santosa Andrew E. , Fekete Alan , Scholz Bernhard
Published: November 2012

The technological advances in wireless sensor network (WSN) enable the development of complex applications including health monitoring, environmental sampling, and disaster area monitoring. WSN applications deploy battery‐powered sensors at remote locations for long periods. The development of energy‐efficient and complex WSN applications therefore requires in‐depth embedded systems programming skills that are normally not found in domain experts. So that this challenge can be overcome, programming environments for WSN need to offer a high degree of productivity, flexibility, and efficiency at the same time. In this work, we present Curracurrong, a development environment for WSNs that is based on expressing queries with stream programming. A query is represented as a stream graph consisting of stream operators and communication channels. Curracurrong provides an extensible stream operator library that adapts to a wide range of applications. It uses a novel placement algorithm that optimizes the energy consumption on sensor nodes. Through a case study, we demonstrate the productivity and flexibility of our system. We conduct experiments that evaluate the energy efficiency of our optimized operator placement algorithm. Copyright © 2012 John Wiley & Sons, Ltd.
Facilitation of fear extinction by the 5‐HT1A receptor agonist tandospirone: Possible involvement of dopaminergic modulation
Authors: Saito Yasuhiro , Matsumoto Machiko , Yanagawa Yoshiki , Hiraide Sachiko , Inoue Sumiyoshi , Kubo Yasunori , Shimamura Kei‐Ichi , Togashi Hiroko
Published: November 2012

Fear extinction‐based exposure treatment is an important component of psychotherapy for anxiety disorders such as posttraumatic stress disorder (PTSD). Recent studies have focused on pharmacological approaches combined with exposure therapy to augment extinction. In this study, we elucidated the therapeutic potential of the serotonin 1A (5‐HT1A) receptor agonist tandospirone compared with the effects of the N‐methyl‐D‐aspartate partial agonist D‐cycloserine (DCS), focusing on the possible involvement of dopaminergic mechanisms. We used a rat model of juvenile stress [aversive footshock (FS)] exposure during the third postnatal week (3wFS). The 3wFS group exhibited extinction deficit reflected in sustained fear‐related behavior and synaptic dysfunction in the hippocampal CA1 field and medial prefrontal cortex (mPFC), which are responsible for extinction processes. Tandospirone administration (5 mg/kg, i.p.) before and after the extinction trials ameliorated both the behavioral deficit and synaptic dysfunction, i.e., synaptic efficacy in the CA1 field and mPFC associated with extinction training and retrieval, respectively, was potentiated in the tandospirone‐treated 3wFS group. Extracellular dopamine release in the mPFC was increased by extinction retrieval in the non‐FS control group. This facilitation was not observed in the 3wFS group; however, tandospirone treatment increased cortical dopamine levels after extinction retrieval. DCS (15 mg/kg, i.p.) also ameliorated the extinction deficit in the 3wFS group, but impaired extinction in the non‐FS control group. These results suggest that tandospirone has therapeutic potential for enhancing synaptic efficacy associated with extinction processes by involving dopaminergic mechanisms. Pharmacological agents that target cortical dopaminergic systems may provide new insights into the development of therapeutic treatments of anxiety disorders, including PTSD. © Synapse, 2013. © 2012 Wiley Periodicals, Inc.
Columnar distribution of catecholaminergic neurons in the ventrolateral periaqueductal gray and their relationship to efferent pathways
Authors: Suckow Shelby K. , Deichsel Emily L. , Ingram Susan L. , Morgan Michael M. , Aicher Sue A.
Published: November 2012

The periaqueductal gray (PAG) is a critical brain region involved in opioid analgesia and provides efferents to descending pathways that modulate nociception. In addition, the PAG contains ascending pathways to regions involved in the regulation of reward, including the substantia nigra (SN) and the ventral tegmental area (VTA). SN and VTA contain dopaminergic neurons that are critical for the maintenance of positive reinforcement. Interestingly, the PAG is also reported to contain a population of dopaminergic neurons. In this study, the distribution of catecholaminergic neurons within the ventrolateral (vl) PAG was examined using immunocytochemical methods. In addition, the catecholaminergic PAG neurons were examined to determine whether these neurons are integrated into ascending (VTA, SN) and descending rostral ventral medulla (RVM) efferent pathways from this region. The immunocytochemical analysis determined that catecholaminergic neurons in the PAG are both dopaminergic and noradrenergic and these neurons have a distinct rostrocaudal distribution within the ventrolateral column of PAG. Dopaminergic neurons were concentrated rostrally and were significantly smaller than noradrenergic neurons. Combined immunocytochemistry and tract tracing methods revealed that catecholaminergic neurons are distinct from, but closely associated with, both ascending and descending efferent projection neurons. Finally, by electron microscopy, catecholaminergic neurons showed close dendritic appositions with other neurons in PAG, suggesting a possible nonsynaptic mechanism for regulation of PAG output by these neurons. In conclusion, our data indicate that there are two populations of catecholaminergic neurons in the vlPAG that form dendritic associations with both ascending and descending efferents suggesting a possible nonsynaptic modulation of vlPAG neurons. Synapse, 2013. © 2012 Wiley Periodicals, Inc.
In vitro binding of a radio‐labeled positive allosteric modulator for metabotropic glutamate receptor subtype 5
Authors: Zysk John R. , Spear Nathan , Fieles William , Stein Mark M. , Sygowski Linda S. , King Megan M. , Hoesch Valerie , Hastings Richard , Brockel Becky , Do Mylinh , Ström Peter , Gadient Reto , Chhajlani Vijay , Elmore Charles S. , Maier Donna L
Published: November 2012

The positive allosteric modulator (PAM) binding site for metabotropic glutamate receptor subtype 5 (mGlu5) lacks a readily available radio‐labeled tracer fordetailed structure‐activity studies. This communication describes a selective mGlu5 compound, 7‐methyl‐2‐(4‐(pyridin‐2‐yloxy)benzyl)‐5‐(pyridin‐3‐yl)isoindolin‐1‐one (PBPyl) that binds with high affinity to human mGlu5 and exhibits functional PAM activity. Analysis of PBPyl by FLIPR revealed an EC50 of 87 nM with an 89% effect in transfected HEK293 cells and an EC50 of 81 nM with a 42% effect in rat primary neurons. PBPyl exhibited 5‐fold higher functional selectivity for mGlu5 in a full mGlu receptor panel. Unlabeled PBPyl was tested for specific binding using a liquid chromatography mass spectrometry (LC/MS/MS)‐based filtration binding assay and exhibited 40% specific binding in recombinant membranes, a value higher than any candidate compound tested. In competition binding studies with [3H]MPEP, the mGlu5 receptor negative allosteric modulator (NAM), PBPyl exhibited a k
i value of 34 nM. PBPyl also displaced [3H]ABP688, a mGluR5 receptor NAM, in tissue sections from mouse and rat brain using autoradiography. Areas of specific binding included the frontal cortex, striatum and nucleus accumbens. PBPyl was radiolabeled to a specific activity of 15 Ci/mmol and tested for specific binding in a filter plate format. In recombinant mGlu5b membranes, [3H] PBPyl exhibited saturable binding with a Kd value of 18.6 nM. In competition binding experiments, [3H] PBPyl was displaced by high affinity mGlu5 positive and negative modulators. Further tests showed that PBPyl displays less than optimal characteristics as an in vivo tool, including a high volume of distribution and ClogP, making it more suitable as an in vitro compound. However, as a first report of direct binding of an mGlu5 receptor PAM, this study offers value toward the development of novel PET imaging agents for this important therapeutic target. Synapse, 2013. © 2012 Wiley Periodicals, Inc.
Periventricular nodular heterotopia on prenatal ultrasound and magnetic resonance imaging
Authors: Blondiaux E. , Sileo C. , Nahama‐Allouche C. , Moutard M. L. , Gelot A. , Jouannic J. M. , Ducou le Pointe H. , Garel C.
Published: November 2012

Objectives

To describe the prenatal ultrasound and magnetic resonance imaging (MRI) findings suggestive of periventricular nodular heterotopia (PNH).

Methods

This retrospective case series included fetuses referred to our institution for brain MRI between 2007 and 2012, which were diagnosed with PNH and confirmed by postnatal MRI or autopsy. The type of PNH, associated ventriculomegaly and associated malformations are reported.

Results

We included 11 fetuses (nine female, two male) with a mean gestational age at diagnosis of 31 (range, 23–34) weeks. PNH lesions were small and diffuse (n = 7), large and multiple (n = 1) or single (n = 3). A targeted ultrasound examination performed before fetal MRI missed the diagnosis in four cases (one diffuse and three single); a further ultrasound examination performed after MRI diagnosed PNH in two of these four cases. Ventriculomegaly was present in six cases (four unilateral and two bilateral). PNH appeared in all cases as nodules of intermediate echogenicity protruding into the ventricular lumen. In all cases of diffuse PNH, the frontal horns and bodies of the lateral ventricles appeared square in shape on coronal view, with irregular borders on axial view. Associated cerebral malformations were observed in seven cases and included corpus callosal agenesis (n = 4, with additional malformations in two) and retrocerebellar cyst (n = 3). Extracerebral malformations were also present in two cases. Maternal MRI was performed in five of the six cases of isolated small and diffuse PNH in female fetuses, and demonstrated PNH in two of these.

Conclusion

PNH is underdiagnosed at prenatal ultrasound, even on targeted scans. Irregular ventricular borders on axial view and irregular square‐shaped lateral ventricles on coronal view are suggestive of PNH at prenatal ultrasound. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.
Evaluation of cervical stiffness during pregnancy using semiquantitative ultrasound elastography
Authors: Hernandez‐Andrade E. , Hassan S. S. , Ahn H. , Korzeniewski S. J. , Yeo L. , Chaiworapongsa T. , Romero R.
Published: November 2012

Objective

To evaluate cervical stiffness during pregnancy using ultrasound‐derived elastography, a method used to estimate the average tissue displacement (strain) within a defined region of interest when oscillatory compression is applied.

Methods

Strain was calculated in two regions of interest, the endocervical canal and the entire cervix, from three anatomical planes of the cervix: mid‐sagittal in the plane used for cervical length measurement and in cross‐sectional planes located at the internal and external cervical os. Associations between strain values, method of ascertainment and patient characteristics were assessed using linear mixed models to account for within‐subject correlation. Inter‐rater agreement in defining the degree of cervical stiffness was evaluated in 120 regions of interest acquired by two operators in 20 patients.

Results

A total of 1557 strain estimations were performed in 262 patients at 8–40 weeks of gestation. Adjusting for other sources of variation, (1) cervical tissue strain estimates obtained in the endocervical canal were on average 33% greater than those obtained in the entire cervix; (2) measurements obtained in the cross‐sectional plane of the external cervical os and sagittal plane were 45% and 13% greater than those measured in the cross‐sectional plane of the internal cervical os, respectively; (3) mean strain rates were 14% and 5% greater among parous women with and without a history of preterm delivery compared with those of nulliparous women, respectively, and were on average 13% greater among women with a cervical length of between 25 and 30 mm compared to those with a cervical length of > 30 mm; and (4) cervical tissue strain was more strongly associated with cervical length than with gestational age.

Conclusion

Semiquantitative elastography can be employed to evaluate changes in cervical stiffness during pregnancy.
Super-Ehlers in any dimension
Authors: Ferrara Sergio , Marrani Alessio , Trigiante Mario
Published: November 2012

Abstract

We classify the enhanced helicity symmetry of the Ehlers group to extended supergravity theories in any dimension. The vanishing character of the pseudo-Riemannian cosets occurring in this analysis is explained in terms of Poincaré duality .The latter resides in the nature of regularly embedded quotient subgroups which are noncompact rank preserving.
Intermittent, moderate-intensity aerobic exercise for only eight weeks reduces arterial stiffness: evaluation by measurement of stiffness parameter and pressure–strain elastic modulus by use of ultrasonic echo tracking
Authors: Tanaka Midori , Sugawara Motoaki , Ogasawara Yasuo , Izumi Tadafumi , Niki Kiyomi , Kajiya Fumihiko
Published: November 2012

Background and purpose

Aerobic exercise has been reported to be associated with reduced arterial stiffness. However, the intensity, duration, and frequency of aerobic exercise required to improve arterial stiffness have not been established. In addition, most reports base their conclusions on changes in pulse wave velocity, which is an indirect index of arterial stiffness. We studied the effects of short-term, intermittent, moderate-intensity exercise training on arterial stiffness based on measurements of the stiffness parameter (β) and pressure–strain elastic modulus (E
p), which are direct indices of regional arterial stiffness.

Methods

A total of 25 young healthy volunteers (18 men) were recruited. By use of ultrasonic diagnostic equipment we measured β and E
p of the carotid artery before and after 8 weeks of exercise training.

Results

After exercise training, systolic pressure (P
s), diastolic pressure (P
d), pulse pressure, systolic arterial diameter (D
s), and diastolic arterial diameter (D
d) did not change significantly. However, the pulsatile change in diameter ((D
s − D
d)/D
d) increased significantly, and β and E
p decreased significantly.

Conclusions

For healthy young subjects, β and E
p were reduced by intermittent, moderate-intensity exercise training for only 8 weeks.
The Predictive Validity of Subjective Mortality Expectations: Evidence From the Health and Retirement Study
Authors: Elder Todd E.
Published: November 2012

Several recent studies suggest that individual subjective survival forecasts are powerful predictors of both mortality and behavior. Using 15 years of longitudinal data from the Health and Retirement Study, I present an alternative view. Across a wide range of ages, predictions of in-sample mortality rates based on subjective forecasts are substantially less accurate than predictions based on population life tables. Subjective forecasts also fail to capture fundamental properties of senescence, including increases in yearly mortality rates with age. To shed light on the mechanisms underlying these biases, I develop and estimate a latent-factor model of how individuals form subjective forecasts. The estimates of this model’s parameters imply that these forecasts incorporate several important sources of measurement error that arguably swamp the useful information they convey.
Short‐ versus long‐term prediction of dementia among subjects with low and high educational levels
Authors: Chary Emilie , Amieva Hélène , Pérès Karine , Orgogozo Jean‐Marc , Dartigues Jean‐François , Jacqmin‐Gadda Hélène
Published: November 2012

Background

Using simple measures of cognition and disability in a prospective community‐living cohort of normal elderly persons, the main objectives of our study were to distinguish short‐ and long‐term predictors for dementia according to educational level and to propose a tool for early detection of subjects at high risk of dementia.

Methods

Data derived from the French cohort study Paquid (Personnes Agées QUID), which included 3777 subjects, older than 65 years of age, who were followed for a 20‐year period. The risk of dementia at 3 years and 10 years was estimated by logistic regression for repeated measures combining data from all the 3‐ and 10‐year windows throughout the follow‐up. Predictors included disability assessed by the number of dependent items among four instrumental activities of daily living (IADLs), four neuropsychological tests, five Mini‐Mental State Examination (MMSE) subtests, and four items of subjective memory complaints.

Results

Of the 2882 included subjects, the number of IADLs remained a predictor of short‐ and long‐term conversion to dementia for those with low educational level (combined with only one cognitive test) whereas the best predictors for more educated subjects combined subjective memory complaints and memory and executive function tests. The episodic memory subtest was the only predictive MMSE subtest. In the high‐education‐level group, the areas under the receiver–operating characteristic curve of the selected models were 0.85 for 3‐year prediction and 0.78 for 10‐year prediction.

Conclusion

Early predictors of dementia are different according to educational level. Among subjects reaching the secondary school level, early detection of those at high risk of dementia is possible with good predictive performance, with a few simple objective and subjective cognitive evaluations.
Intracerebral propagation of Alzheimer's disease: Strengthening evidence of a herpes simplex virus etiology
Authors: Ball Melvyn J. , Lukiw Walter J. , Kammerman Eli M. , Hill James M.
Published: November 2012

Background

A faulty human protein, abnormally phosphorylated tau, was recently publicized to spread “like a virus” from neuron to neuron in Alzheimer's patients’ brains. For several decades, we have been amassing arguments showing that herpes simplex virus type 1 (HSV‐1), not p‐tau, propagates this interneuronal, transsynaptic pathologic cascade.

Methods

We reiterate convincing data from our own (and other) laboratories, reviewing the first anatomic foothold neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic immunosurveillance cellularity of the trigeminal ganglia wherein HSV‐1 awakens from latency to reactivate; the inabilities of p‐tau protein's physical properties to promote it to jump synapses; the amino acid homology between human p‐tau and VP22, a key target for phosphorylation by HSV serine/threonine–protein kinase UL13; and the exosomic secretion of HSV‐1–infected cells’ L‐particles, attesting to the cell‐to‐cell passage of microRNAs of herpesviruses.

Results

The now‐maturing construct that reactivated HSV‐1 best accounts for the intracerebral propagation of AD changes in the human brain should at last seem highly attractive. This hypothesis might even explain statins' apparent mechanism in some studies for lowering AD incidence.

Conclusion

Provided that funding agencies will quickly ignite a new realm of investigation, the rejuvenated enthusiasm for testing this optimistic construct holds incalculable potential for rapid, efficacious clinical application, through already available and relatively safe antiviral therapeutics.
Molecular phenotype predicts sensitivity of squamous cell carcinoma of the head and neck to epidermal growth factor receptor inhibition
Authors: Young Natalie R. , Liu Jing , Pierce Carolyn , Wei Tai-Fen , Grushko Tatyana , Olopade Olufunmilayo I. , Liu Wanqing , Shen Christine , Seiwert Tanguy Y. , Cohen Ezra E.W.
Published: November 2012

Despite nearly universal expression of the wild‐type epidermal growth factor receptor (EGFR) and reproducible activity of EGFR inhibitors in patients with squamous cell carcinoma of the head and neck (SCCHN), the majority of patients will not have objective responses. The mechanisms of this intrinsic resistance are not well established. We hypothesized that sensitivity to EGFR inhibitors can be predicted based on the inhibitors' effects on downstream signaling. Cell viability assays were used to assess sensitivity to the EGFR inhibitor gefitinib (ZD1839) in 8 SCCHN cell lines. Fluorescence in‐situ hybridization showed the two most sensitive lines to be highly gene‐amplified for EGFR. Western blotting confirmed that phosphoEGFR was inhibited at low concentrations of gefitinib in all lines tested. Phosphorylation of downstream signaling protein AKT was inhibited in sensitive lines while inhibition of phosphoERK displayed no relationship to gefitinib efficacy. Phosphatase and tensin homolog (PTEN) expression was evident in all cell lines. Activating PIK3CA mutations were found in two resistant cell lines where pAKT was not inhibited by gefitinib. In resistant cell lines harboring PIK3CA mutations, a PI3K inhibitor, LY294002, or AKT siRNA reduced cell viability with an additive effect demonstrated in combination with gefitinib. Additionally, LY294002 alone and in combination with gefitinib, was effective at treating PIK3CA mutated tumors xenografted into nude mice. Taken together this suggests that constitutively active AKT is a mechanism of intrinsic gefitinib resistance in SCCHN. This resistance can be overcome through targeting of the PI3K/AKT pathway in combination with EGFR inhibition.
Factors Associated With Home Discharge After Rehabilitation Among Male Veterans With Lower Extremity Amputation
Authors: Kurichi Jibby E. , Ripley Diane Cowper , Xie Dawei , Kwong Pui L. , Bates Barbara E. , Stineman Margaret G.
Published: November 2012

Objective

To determine the patient‐, treatment‐, and facility‐level factors that are associated with home discharge among male veterans with lower extremity amputation who received inpatient rehabilitation after surgery.

Design

A retrospective observational study.

Setting

Veterans Affairs Medical Centers.

Participants

This study included 1480 male veterans.

Methods

Generalized estimating equation models were used to model the likelihood of home discharge to account for within‐facility clustering. We reported odds ratios (ORs) and 95% confidence intervals (95% CIs).

Main Outcome Measurement

Discharged to home.

Results

There were a total of 1163 (78.6%) veterans who were discharged home after the surgical hospitalization, compared with other locations. Patients who were married were more likely to be discharged home compared with patients who were not married (OR = 1.51, 95% CI = 1.14‐1.99, P < .01). Compared with being transferred from another hospital or extended care, patients who were admitted from home were far more likely to be discharged home (OR = 8.43, 95% CI = 5.48‐12.96, P < .0001). Patients with evidence of local significant infection were less likely to be discharged home (OR = 0.57, 95% CI = 0.39‐0.83, P < .01), as were patients with evidence of congestive heart failure (OR = 0.62, 95% CI = 0.45‐0.85, P < .01) or depression (OR = 0.63, 95% CI = 0.40‐0.98, P = .04). Veterans with greater discharge motor Functional Independence Measure scores were more likely to be discharged home (OR = 1.23, 95% CI = 1.16‐1.31 per 10‐point increase in discharge Functional Independence Measure motor score, P < .0001). Conversely, patients undergoing procedures for ongoing active cardiac pathology were less likely to be discharged home (OR = 0.55, 95% CI = 0.37‐0.81, P < .01).

Conclusions

This study showed a strong association between the sociological factors of marital status and living location before hospitalization and home discharge. The significance of discharge functional status highlights the importance of addressing the expected care burden once patients are discharged home.
Designing and Implementing a System for Tracking Functional Status After Stroke: A Feasibility Study
Authors: Sandel M. Elizabeth , Jette Alan M. , Appelman Jed , Terdiman Joseph , TeSelle Marian , Delmonico Richard L. , Wang Hua , Camicia Michelle , Rasch Elizabeth K. , Brandt Diane E. , Chan Leighton
Published: November 2012

Objective

To determine the feasibility of tracking stroke patients' functional outcomes in an integrated health system across a care continuum using the computer version of the Activity Measure of Post‐Acute Care (AM‐PAC).

Setting

A large integrated health care system in northern California.

Participants

A total of 222 stroke patients (aged ≥18 years) who were hospitalized after an acute cerebrovascular accident.

Methods

An AM‐PAC assessment was made at discharge from sites of care, including acute hospital, inpatient rehabilitation hospital, skilled nursing facility, home during home care, and outpatient settings. Assessments also were completed in the patient's home at 6 months. Data from the AM‐PAC program were integrated with the health care system's databases.

Main Outcome Measurements

(1) AM‐PAC administration time at the various sites of care; (2) assessment of a floor or a ceiling effect; and (3) administrative burden of tracking participants.

Results

AM‐PAC assessment sessions averaged 7.9 minutes for data acquisition in 3 domains: Basic Mobility, Activities of Daily Living, and Applied Cognition. Participants answered, on average, 27 AM‐PAC questions per session. A small ceiling effect was observed at 6 months, and there was a larger ceiling effect when the instrument was administered in an institution, ie, when the AM‐PAC institutional item bank was used rather than the community item bank. It was feasible to track patients and to assess their function using the AM‐PAC instrument from institutional to community settings. Implementation of the AM‐PAC in clinical environments, and the success of the project, were influenced by instrumental, technological, operational, resource, and cultural factors.

Conclusions

This study demonstrates the feasibility of implementing a single functional outcome instrument in clinical and community settings to measure rehabilitation functional outcomes of stroke patients. Integrating the AM‐PAC measurement system into clinical workflows and the electronic medical record could provide assistance to clinicians for medical decision making, functional prognostication, and discharge planning.
FAMILY FOOD INSECURITY AND NUTRITIONAL RISK IN ADOLESCENTS FROM A LOW-INCOME AREA OF RIO DE JANEIRO, BRAZIL
Authors: LOPES TAÍS S. , SICHIERI ROSELY , SALLES-COSTA ROSANA , VEIGA GLORIA V. , PEREIRA ROSANGELA A.
Published: November 2012

The study objective was to analyse the association between food insecurity and the weight and height status of adolescents from a low-income area in the metropolitan region of Rio de Janeiro, Brazil. The population-based cross-sectional survey included 523 adolescents aged 12–18 years, selected by a three-stage cluster sample. Dietary intake was ascertained with a food frequency questionnaire and family food insecurity was assessed with a validated questionnaire. The analysis estimated weighted means of energy and nutrient intakes by families' socioeconomic characteristics and the association between dietary intake with overweight and stunting. The prevalence of mild family food insecurity was 36%, and 24% of the families reported moderate or severe food insecurity. Overweight prevalence was 24%, and the prevalence of stunting was 9%, with no significant differences between sex or age groups. Family food insecurity was associated with unfavourable socioeconomic characteristics, but there was no association between socioeconomic characteristics (including family food insecurity) and overweight or stunting. Moderate or severe family food insecurity was inversely associated with intake of protein and calcium. In addition, stunting was associated with low calcium and iron intake. The co-existence of family food insecurity with overweight and stunting implies a high nutritional risk for adolescents from poor areas of Rio de Janeiro. Nevertheless, the observed absence of a statistical association between family food insecurity and weight status attests to the complexity of this issue.
Estimating patterns of vulnerability in a changing landscape: a case study of New Zealand's indigenous grasslands
Authors: WEEKS EMILY S. , OVERTON JACOB M. , WALKER SUSAN
Published: November 2012

Effective conservation planning must anticipate the rates and patterns of dynamic threats to biodiversity, such as rapid changes in land use. Poor understanding and prediction of drivers and patterns of conversion of habitat can hinder assessments of the relative vulnerability of areas of remaining indigenous habitat to conversion, and identification of habitats in most immediate need of protection. Methods developed to model vulnerability to conversion vary in their complexity and applicability to conservation management. Generalized additive models provide a simple robust method to explore predictors and patterns of land-use conversion, and may be used to predict future patterns of conversion using recent land conversion data. This paper provides the first data-derived and statistically validated measurement of the vulnerability of New Zealand's indigenous grasslands to conversion. Higher altitude and more marginal (for agriculture and forestry) land showed greater conversion, and models based on earlier conversion patterns performed more poorly in predicting current patterns of conversion. Up-to-date land conversion data appear crucial for accurately predicting future vulnerability to habitat conversion.
The Use and Abuse of the Law: Public Opinion and United Methodist Church Trials of Ministers Performing Same-Sex Union Ceremonies
Authors: Waldrep Christopher
Published: November 2012

Law in the United Methodist Church (UMC) is a product of democracy, written by elected delegates to a legislative body, recorded in a book entitledThe Book of Discipline of the United Methodist Church. As “a Book of Law,” theBook of Disciplineis “the only official and authoritative Book of Law of The Methodist Church,” according to the Methodist Church's Judicial Council in a landmark 1953 ruling. Despite this declaration, the Judicial Council had no idea in 1953 that it had addressed a question that in 20 years would divide not just the Methodists, but Americans and American Christians generally. In the last 30 years of the twentieth century, controversies over homosexuality led American Christians into debates over the role law should play in their churches, while Americans as a whole debated the role churches should play in their law. United Methodist conservatives discovered that by rallying populist majorities to rewrite church law, they could then use church trials to roll back what they saw as excesses from the 1960s still plaguing American society. Writing any law is necessarily a political process, but in the UMC, church trials became political battlegrounds as well, contests to determine if rank-and-file clergy approved church rules against anything resembling a same-sex marriage.
The Fugitive Slave Clause and the Antebellum Constitution
Authors: Baker H. Robert
Published: November 2012

Among the most long-lasting constitutional controversies in the antebellum era was the interpretation of the fugitive slave clause. It was the subject of repeated legislative and judicial construction at both the state and the federal level. It raised delicate questions about federalism and the balancing of property rights and personal liberty. Slaveholders and abolitionists brought irreconcilable constitutional positions to the table, ultimately dividing Northerners from Southerners. However, it was not just divergent political commitments that made it difficult to fix a stable meaning to the fugitive slave clause. The text itself was ambiguous enough to make it amenable to multiple interpretations. For precisely this reason, an examination of the changing interpretations of the fugitive slave clause uncovers antebellum constitutional praxis, allowing us to see how historical actors interpreted the Constitution and how those interpretations shifted over time.
THE ACCELERATOR PRINCIPLE AT THE CORE OF FRISCH’S 1933 ROCKING HORSE MODEL
Authors: DUPONT-KIEFFER ARIANE
Published: November 2012

This paper aims to detail Frisch’s choice of setting the accelerator principle at the core of his impulse-propagation model (1933a), referred to as the “rocking horse model.” The innovative aspects of this model rest not only on the rise of macrodynamics regarding the equilibrium concept but also on the reformulation of business cycles in terms of production of capital goods. This is a deliberate choice, which relies on his work on business cycles started in 1927, and can be obviously traced back to his debate with John Maurice Clark and the American Institutionalists, but relies more deeply on a specific appropriation of Norwegian approach to this principle.
THE MACHINE IN ADAM SMITH’S ECONOMIC AND WIDER THOUGHT
Authors: ASPROMOURGOS TONY
Published: November 2012

This paper exhaustively examines all Adam Smith’s references to “machines,” including machine metaphors or analogies, with a view to a comprehensive interpretation of the significance of the machine in his thought as a whole. By bringing together all Smith’s references to machines (and variants of that term), as well as his references to related phenomena, mechanics and engines (and variants), the totality of the various different kinds of uses of these terms assists in clarifying the meaning of each of them. However, this exercise is undertaken particularly with a view to the significance of machines in Smith’s political economy.
THE HISTORY OF ATTITUDES TOWARDS INTERDEPENDENT PREFERENCES
Authors: DRAKOPOULOS STAVROS A.
Published: November 2012

The notion of interdependent preferences has a long history in economic thought. In its general form, it can be found in the works of authors such as Hume, Rae, Genovesi, Smith, Marx, and Mill, among others. In the twentieth century, the idea became more widespread mainly through the works of Veblen and Duesenberry. Recently, an increasing number of theorists are interested in issues such as reference income, relative consumption, and positional goods, which are all based on the concept of interdependent preferences. However, such preferences were never part of the corpus of orthodox theory. For instance, although Pareto and Marshall were aware of their existence, they did not advocate their incorporation into orthodox economic theory. This paper argues that the structure of mainstream economic methodology and the challenging theoretical implications of adopting interdependent preferences were two possible reasons for the mainstream rejection. The discussion includes the more recent orthodox attitudes towards such preferences.
From Maycomb to Nuremberg: cinematic visions of law, legal actors and American ways
Authors: Davies Susanne
Published: November 2012

This article examines the representations of law and legal actors offered within two classic American films:To Kill a MockingbirdandJudgment at Nuremberg. It has previously been argued that these films belong to a ‘heroic tradition’ within American cinema; one that idealises both men of law and man-made law and that had its golden age from the mid-1950s through to the end of the 1960s. It is argued here that these films offer a more complex and far less certain portrayal of the law and legal actors. This is examined first by considering the context in which these films were made, and second, the depictions of law and legal actors that they offer.
German sociology of law: a case of path dependency
Authors: Machura Stefan
Published: November 2012

German sociology of law has developed along a peculiar path which is still shaping its development today. Unlike other special areas of sociology that extended sociologists' inquiry to new fields, the sociology of law was founded mainly by lawyers in the early twentieth century as a tool for enhanced professional practice. The sociology of law became part of a struggle over the academic identity of jurisprudence. This first wave of German sociology of law was then overshadowed by a second wave in the 1960s and 1970s along the lines of legal reform and radical scholarship. Today, the sociology of law in Germany is receiving renewed interest under the labels of empirical legal research and of inter- and transdisciplinarity, and scholars are to a large degree still driven by political interests.
Recruiting Respondents for a Mobile Phone Panel
Authors: Busse Britta , Fuchs Marek
Published: November 2012

This paper is concerned with the optimal wording of the recruitment question for a mobile phone panel survey in Germany. In order to learn more about the effects of different recruitment questions on the size and composition of the panel, we experimented with four different recruitment question versions. We analyzed the effectiveness of each question version with regard to three indicators: (1) What is the proportion of respondents who agree to take part in the panel? (2) Will the respondents who agreed to become panel members actually participate in the panel? (3) To what extent are differential nonresponse biases induced into the panel, since each question version may have differential effects on the composition of the recruited sample? Findings are discussed in light of an adaptive field work design: We propose a tailored request for participation for each individual respondent based on sociodemographic and other relevant variables.
The Role of Job Satisfaction, Job Ambivalence, and Emotions at Work in Predicting Organizational Citizenship Behavior
Authors: Ziegler René , Schlett Christian , Casel Kerstin , Diehl Michael
Published: November 2012

Various mostly cross-sectional studies have established that job satisfaction is related to organizational citizenship behavior (OCB). A major goal of the present study was to show that job ambivalence (i.e., the coexistence of positive and negative job evaluations) moderates the job satisfaction-OCB relationship. To this end, job satisfaction, job ambivalence, frequency of positive and negative emotions at work, dispositional positive and negative affectivity, and OCB were gathered from employees at time 1. About 2 months later, OCB was assessed by both peer-ratings and self-ratings. As predicted, the relationship between job satisfaction and both peer-rated and self-rated OCB was stronger the lower the experienced job ambivalence. Further findings showed that job satisfaction mediated the relationship between positive emotions and OCB, and that this indirect effect of positive emotions was conditional on low job ambivalence. Negative emotions, though negatively related to OCB, did not contribute to predicting OCB beyond positive emotions.
Reducing hydrologic model uncertainty in monthly streamflow predictions using multimodel combination
Authors: Li Weihua , Sankarasubramanian A.
Published: November 2012

Model errors are inevitable in any prediction exercise. One approach that is currently gaining attention in reducing model errors is by combining multiple models to develop improved predictions. The rationale behind this approach primarily lies on the premise that optimal weights could be derived for each model so that the developed multimodel predictions will result in improved predictions. A new dynamic approach (MM‐1) to combine multiple hydrological models by evaluating their performance/skill contingent on the predictor state is proposed. We combine two hydrological models, “abcd” model and variable infiltration capacity (VIC) model, to develop multimodel streamflow predictions. To quantify precisely under what conditions the multimodel combination results in improved predictions, we compare multimodel scheme MM‐1 with optimal model combination scheme (MM‐O) by employing them in predicting the streamflow generated from a known hydrologic model (abcd model orVICmodel) with heteroscedastic error variance as well as from a hydrologic model that exhibits different structure than that of the candidate models (i.e., “abcd” model or VIC model). Results from the study show that streamflow estimated from single models performed better than multimodels under almost no measurement error. However, under increased measurement errors and model structural misspecification, both multimodel schemes (MM‐1 and MM‐O) consistently performed better than the single model prediction. Overall, MM‐1 performs better than MM‐O in predicting the monthly flow values as well as in predicting extreme monthly flows. Comparison of the weights obtained from each candidate model reveals that as measurement errors increase, MM‐1 assigns weights equally for all the models, whereas MM‐O assigns higher weights for always the best‐performing candidate model under the calibration period. Applying the multimodel algorithms for predicting streamflows over four different sites revealed that MM‐1 performs better than all single models and optimal model combination scheme, MM‐O, in predicting the monthly flows as well as the flows during wetter months.
Impacts of nonuniform flow on estimates of vertical streambed flux
Authors: Cuthbert M. O. , Mackay R.
Published: November 2012

Key Points

Non‐uniform flow fields cause errors in 1D heat tracer flux estimation methods

Non‐vertical flow won't necessarily cause such errors

Non‐uniform flow leads to differences in hydraulic and heat tracer estimates