bluuebunny/crossref_metadata_2025 huggingface dataset:
Regression Analysis of Longitudinal Data with Time‐Dependent Covariates and Informative Observation Times
Authors: SONG XINYUAN , MU XIAOYUN , SUN LIUQUAN
Published: March 2012

Abstract.  Longitudinal data frequently occur in many studies, and longitudinal responses may be correlated with observation times. In this paper, we propose a new joint modelling for the analysis of longitudinal data with time‐dependent covariates and possibly informative observation times via two latent variables. For inference about regression parameters, estimating equation approaches are developed and asymptotic properties of the proposed estimators are established. In addition, a lack‐of‐fit test is presented for assessing the adequacy of the model. The proposed method performs well in finite‐sample simulation studies, and an application to a bladder tumour study is provided.
Prefrontal cortex rTMS enhances action naming in progressive non‐fluent aphasia
Authors: Cotelli M. , Manenti R. , Alberici A. , Brambilla M. , Cosseddu M. , Zanetti O. , Miozzo A. , Padovani A. , Miniussi C. , Borroni B.
Published: March 2012

Background and purpose:  Progressive non‐fluent aphasia (PNFA) is a neurodegenerative disorder that is characterized by non‐fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) improves action naming in healthy subjects and in subjects with Alzheimer’s disease.

Purpose:  To investigate whether the modulation of DLPFC circuits by rTMS modifies naming performance in patients with PNFA.

Methods:  Ten patients with a diagnosis of PNFA were enrolled. High‐frequency rTMS was applied to the left and right DLPFC and the sham (i.e. placebo) condition during object and action naming. A subgroup of patients with semantic dementia was enrolled as a comparison group.

Results:  A repeated‐measure anova with stimulus site (sham, left and right rTMS) showed significant effects. Action‐naming performances during stimulation of both the left and right DLPFC were better than during placebo stimulation. No facilitating effect of rTMS to the DLPFC on object naming was observed. In patients with a diagnosis of semantic dementia, no effect of stimulation was reported.

Conclusions:  Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required.
MOLECULAR PHYLOGENY AND TAXONOMY OF THE AEGAGROPILA CLADE (CLADOPHORALES, ULVOPHYCEAE), INCLUDING THE DESCRIPTION OF AEGAGROPILOPSIS GEN. NOV. AND PSEUDOCLADOPHORA GEN. NOV.1
Authors: Boedeker Christian , O’Kelly Charles J. , Star Wim , Leliaert Frederik
Published: March 2012

The Aegagropila clade represents a unique group of cladophoralean green algae occurring mainly in brackish and freshwater environments. The clade is sister to the species‐rich and primarily marine Cladophora and Siphonocladus lineages. Phylogenetic analyses of partial LSU and SSU nrDNA sequences reveal four main lineages within the Aegagropila clade, and allow a taxonomic reassessment. One lineage consists of two marine ‘Cladophora’ species, for which the new genus Pseudocladophora and the new family Pseudocladophoraceae are proposed. For the other lineages, the family name Pithophoraceae is reinstated. Within the Pithophoraceae, the earliest diverging lineage includes Wittrockiella and Cladophorella calcicola, occurring mainly in brackish and subaerial habitats. The two other lineages are restricted to freshwater. One of them shows a strong tendency for epizoism, and consists of Basicladia species and Arnoldiella conchophila. The other lineage includes Aegagropila, Pithophora and a small number of tropical ‘Cladophora’ species. The latter are transferred to the new genus Aegagropilopsis. Previously, polypyramidal pyrenoids had been suggested to be apomorphous for this clade, but we report the finding of both polypyramidal and bilenticular pyrenoids in members of the Pithophoraceae, and thus show that this character has no diagnostic value.
Exercise‐Related QT Interval Shortening with a Peaked T Wave in a Healthy Boy with a Family History of Sudden Cardiac Death
Authors: CHINUSHI MASAOMI , SATO AKINORI , IIJIMA KENICHI , SUZUKI KATUYA , HIROSHI FURUSHIMA , IZUMI DAISUKE , WATANABE HIROSHI , KANAE HASEGAWA , AIZAWA YOSHIFUSA
Published: March 2012

An asymptomatic 15‐year‐old boy, who had a family history of sudden cardiac death, was referred for screening for cardiac disease. The 12‐lead electrocardiogram at rest showed a short QT/QTc(Bazett)/QTc(Fredericia) interval of 320/388/364 ms, but the intervals were further shortened to 200/339/284 ms after the treadmill test concomitant with appearance of a peaked T wave. Other conventional cardiac examinations were normal, but effective refractory period was less than 180 ms in both ventricles, and double ventricular extrastimulation reproducibly induced nonsustained polymorphic ventricular tachycardia. Intravenous administration of epinephrine also induced a short QT interval and a peaked T wave, and a hump was manifested on the T wave of the first postpacing beat with a longer preceding R–R interval. Furthermore, a couple of premature ventricular complexes originated from a similar timing as the hump. Genetic analysis did not show the mutation in KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2, SCN5A genes but revealed single nucleotide polymorphism (C5457T) in SCN5A gene.

(PACE 2012; 35:e239–e242)
Histamine: an undercover agent in multiple rare diseases?
Authors: Pino‐Ángeles Almudena , Reyes‐Palomares Armando , Melgarejo Esther , Sánchez‐Jiménez Francisca
Published: March 2012

Histamine is a biogenic amine performing pleiotropic effects in humans, involving tasks within the immune and neuroendocrine systems, neurotransmission, gastric secretion, cell life and death, and development. It is the product of the histidine decarboxylase activity, and its effects are mainly mediated through four different G‐protein coupled receptors. Thus, histamine‐related effects are the results of highly interconnected and tissue‐specific signalling networks. Consequently, alterations in histamine‐related factors could be an important part in the cause of multiple rare/orphan diseases. Bearing this hypothesis in mind, more than 25 rare diseases related to histamine physiopathology have been identified using a computationally assisted text mining approach. These newly integrated data will provide insight to elucidate the molecular causes of these rare diseases. The data can also help in devising new intervention strategies for personalized medicine for multiple rare diseases.
Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes
Authors: Lee Yun , Sooranna Suren R. , Terzidou Vasso , Christian Mark , Brosens Jan , Huhtinen Kaisa , Poutanen Matti , Barton Geraint , Johnson Mark R. , Bennett Phillip R.
Published: March 2012

The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with ‘functional progesterone withdrawal’ caused through changes in the expression or function of progesterone receptor (PR). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a ‘myometrial inflammation’ via NF‐κB activation. The negative interaction between NF‐κB and PR, may represent a mechanism to account for ‘functional progesterone withdrawal’ at term. Conversely, PR may act to inhibit NF‐κB function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this inter‐relationship, we have used small interfering (si) RNA‐mediated knock‐down of PR in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through PR. We then activated myometrial inflammation using IL‐1β stimulation to determine the role of PR in myometrial inflammation regulation. Through PR‐knock‐down, we found that PR regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize PR‐induced gene expression, of genes normally upregulated via PR. We found that PR does not play a role in repression of pro‐inflammatory gene networks induced by IL‐1β and that only MMP10 was significantly regulated in opposite directions by IL‐1β and PR. We conclude that progesterone acting through PR does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause ‘functional progesterone withdrawal’ but only in the context of genes normally upregulated via PR.
Once or twice‐daily, algorithm‐based intravenous cephazolin for home‐based cellulitis treatment
Authors: Garrett Tim , Harbort Yvonne , Trebble Mary , Docherty Toni
Published: March 2012

Objective: Cellulitis is a common presentation to the ED and a significant cause of hospitalization that can be managed in hospital‐in‐the‐home programmes. Current clinical‐practice guidelines recommend once or twice‐daily i.v. antibiotics; however, there is an absence of data describing the impact of these guidelines in real‐world practice‐based settings. This study aims to describe the safety and effectiveness of home‐based cellulitis treatment according to an online treatment algorithm.

Methods: Over 12 months, 301 patients with a diagnosis of uncomplicated cellulitis requiring i.v. antibiotics and eligible for home‐based therapy completed once‐daily (cephazolin plus probenecid) or twice‐daily (cephazolin alone) treatment, according to the treatment algorithm. Time (days) until non‐progression of cellulitis was the primary outcome measure. Length of stay and treatment‐related side‐effects were also recorded.

Results: The mean time until non‐progression was 2.11 (95% confidence interval [CI] 1.98–2.23) days versus 2.13 (95% CI 1.81–2.45) days for the once‐daily (n = 213) and twice‐daily (n = 88) regimens, respectively (P = 0.92, difference in means 0.02 [95% CI −0.36–0.33]). The corresponding mean length of stay was 6.55 (95% CI 5.96–7.15) days versus 7.67 (95% CI 6.69–8.65) days (P = 0.06, difference in means 1.12 [CI 0.03–1.23]). Treatment‐related side‐effects were reported in 15.5% (33/213 [95% CI 10.6–20.3]) of patients receiving the once‐daily regimen compared with 9.1% (8/88 [95% CI 3.1–15.1]) treated twice‐daily. Application of the once‐daily strategy increased hospital‐in‐the‐home cellulitis‐related treatment capacity by 52% (1396/2688 [95% CI 50–54]).

Conclusions: An online decision support algorithm can support the effective use of a once or twice‐daily treatment regimen for uncomplicated cellulitis. This approach can increase the efficiency and capacity of home‐based therapy, resulting in better alignment of treatment options with clinicians and patients' preferences.
Caisse de dépôt et placement du Québec : Je me souviens …
Authors: Morin Danielle , Megas Sarah
Published: March 2012

Sommaire

La Caisse de dépôt et placement du Québec a été créée dans le courant de la Révolution tranquille qui a débuté le 22 juin 1960 avec l'élection du Parti libéral dont le chef, Jean Lesage, prônait la réappropriation de leur destinée par les Québécois francophones. Ainsi, la contribution au développement économique du Québec était non seulement la raison d'être de la Caisse, mais aussi sa raison d'exister. Cette noble mission a été celle défendue par les gouvernements subséquents jusqu'au début des années 2000. En 2008, alors que des institutions financières que l'on croyait jusque‐là invincibles, comme la banque américaine Lehman Brothers par exemple, faisaient faillite, la Caisse affichait des pertes de 40 milliards $. Nous avançons que la chute de la Caisse a été précipitée par des actions révolutionnaristes, au sens donné par Kahn (2006), prises par les dirigeants de la Caisse et le gouvernement Charest dans les années précédant sa chute. En 2008, la Caisse était devenue d'abord et avant tout un fonds de placement destiné à faire fructifier les avoirs des déposants. Cette mise à K.‐O. de la Caisse illustre éloquemment un revers de la logique de marché lorsque transcrite sans vergogne à l'administration de fonds publics.
Graphene stripper foils
Authors: Pavlovsky Igor , Fink Richard L.
Published: March 2012

Thin carbon and metal foils have been used in heavy ion accelerators for charge stripping. The power dissipated by a particle beam in a foil can be as high as 3 kW or greater, which results in short lifetimes of conventional stripper foils. Graphene stripper foils can overcome critical limitations of other materials due to a unique combination of their exceptional physical properties. The authors have fabricated graphene foils with diameters up to 13 cm and area densities of 0.1 to 3.0 mg/cm2 by reduction of graphene oxide in an aqueous dispersion followed by pressure filtration. The foils were characterized by a number of analytical techniques, including scanning electron microscopy, thermogravimetric analysis, and x-ray photoelectron spectroscopy, and proved their superior mechanical and thermal properties. Preliminary ion beam tests showed that the graphene stripper foils possess up to four times longer lifetime, as opposed to conventional carbon foils.
A computerized scheme for lung nodule detection in multiprojection chest radiography
Authors: Guo Wei , Li Qiang , Boyce Sarah J. , McAdams H. Page , Shiraishi Junji , Doi Kunio , Samei Ehsan
Published: March 2012

Purpose:

Our previous study indicated that multiprojection chest radiography could significantly improve radiologists' performance for lung nodule detection in clinical practice. In this study, the authors further verify that multiprojection chest radiography can greatly improve the performance of a computer‐aided diagnostic (CAD) scheme.

Methods

: Our database consisted of 59 subjects, including 43 subjects with 45 nodules and 16 subjects without nodules. The 45 nodules included 7 real and 38 simulated ones. The authors developed a conventional CAD scheme and a new fusion CAD scheme to detect lung nodules. The conventional CAD scheme consisted of four steps for (1) identification of initial nodule candidates inside lungs, (2) nodule candidate segmentation based on dynamic programming, (3) extraction of 33 features from nodule candidates, and (4) false positive reduction using a piecewise linear classifier. The conventional CAD scheme processed each of the three projection images of a subject independently and discarded the correlation information between the three images. The fusion CAD scheme included the four steps in the conventional CAD scheme and two additional steps for (5) registration of all candidates in the three images of a subject, and (6) integration of correlation information between the registered candidates in the three images. The integration step retained all candidates detected at least twice in the three images of a subject and removed those detected only once in the three images as false positives. A leave‐one‐subject‐out testing method was used for evaluation of the performance levels of the two CAD schemes.

Results

: At the sensitivities of 70%, 65%, and 60%, our conventional CAD scheme reported 14.7, 11.3, and 8.6 false positives per image, respectively, whereas our fusion CAD scheme reported 3.9, 1.9, and 1.2 false positives per image, and 5.5, 2.8, and 1.7 false positives per patient, respectively. The low performance of the conventional CAD scheme may be attributed to the high noise level in chest radiography, and the small size and low contrast of most nodules.

Conclusions

: This study indicated that the fusion of correlation information in multiprojection chest radiography can markedly improve the performance of CAD scheme for lung nodule detection.
Quality of secondary prevention measures in TIA patients: a retrospective cohort study
Authors: Lager K E , Wilson A , Khunti K , Mistri A K
Published: March 2012

Objective

Pharmacological and lifestyle interventions are recommended for the reduction of stroke risk in people who have had a transient ischaemic attack (TIA). This study aimed to investigate the quality of secondary stroke prevention in primary care following diagnosis of TIA in a specialist clinic.

Methods

Quality standards were identified from the Royal College of Physicians (RCP) national clinical guideline for stroke and the general practice Quality and Outcomes Framework (QOF) indicators. Patients who were diagnosed with TIA between February and October 2009 were identified from a TIA clinic database. Achievement of quality standards was assessed 12–24 months following clinic attendance.

Results

General practices were sent structured data collection forms for 233 patients, and the response rate was 80% (n=186). Complete data were available for 163 eligible patients (70%). Overall, 94% were prescribed antithrombotic medication. QOF standards were achieved by 82% for blood pressure (≤150/90 mm Hg) and 61% for total cholesterol (≤5.0 mmol/l). RCP standards were achieved by 35% for blood pressure (≤130/80 mm Hg) and 28% for total cholesterol (<4.0 mmol/l). RCP standards for the provision of dietary and exercise advice were achieved by 29% and 34% of patients, respectively.

Conclusion

Only a minority of TIA patients achieved RCP standards whereas QOF standards were generally well achieved. Substantial benefits in terms of stroke prevention stand to be gained if risk factors are managed in line with more stringent RCP standards.
COEVOLUTIONARY DYNAMICS OF PREDATOR-PREY INTERACTIONS
Authors: ZU JIAN , WANG JINLIANG , TAKEUCHI YASUHIRO
Published: March 2012

In this paper, with the method of adaptive dynamics, we investigate the coevolution of phenotypic traits of predator and prey species. The evolutionary model is constructed from a deterministic approximation of the underlying stochastic ecological processes. Firstly, we investigate the ecological and evolutionary conditions that allow for continuously stable strategy and evolutionary branching. We find that evolutionary branching in the prey phenotype will occur when the frequency dependence in the prey carrying capacity is not strong. Furthermore, it is found that if the two prey branches move far away enough, the evolutionary branching in the prey phenotype will induce the secondary branching in the predator phenotype. The final evolutionary outcome contains two prey and two predator species. Secondly, we show that under symmetric interactions the evolutionary model admits a supercritical Hopf bifurcation if the frequency dependence in the prey carrying capacity is very weak. Evolutionary cycle is a likely outcome of the mutation-selection processes. Finally, we find that frequency-dependent selection can drive the predator population to extinction under asymmetric interactions.
Developmental programming of neonatal pancreatic β-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation
Authors: Rodríguez-Trejo Adriana , Ortiz-López María Guadalupe , Zambrano Elena , Granados-Silvestre María de los Ángeles , Méndez Carmen , Blondeau Bertrand , Bréant Bernadette , Nathanielsz Peter W. , Menjivar Marta
Published: March 2012

Maternal low-protein diets (LP) impair pancreatic β-cell development, resulting in later-life failure and susceptibility to type 2 diabetes (T2D). We hypothesized that intrauterine and/or postnatal developmental programming seen in this situation involve altered β-cell structure and relative time course of expression of genes critical to β-cell differentiation and growth. Pregnant Wistar rats were fed either control (C) 20% or restricted (R) 6% protein diets during pregnancy (1st letter) and/or lactation (2nd letter) in four groups: CC, RR, RC, and CR. At postnatal days 7 and 21, we measured male offspring β-cell fraction, mass, proliferation, aggregate number, and size as well as mRNA level for 13 key genes regulating β-cell development and function in isolated islets. Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. We conclude that LP in pregnancy sets the trajectory of postnatal β-cell growth and differentiation, whereas LP in lactation has smaller effects. We propose that LP promotes differentiation through upregulation of transcription factors that stimulate differentiation at the expense of proliferation. This results in a decreased β-cell reserve, which can contribute to later-life predisposition to T2D.
Coordinate regulation of heterogeneous nuclear ribonucleoprotein dynamics by steroid hormones in the human fallopian tube and endometrium in vivo and in vitro
Authors: Shao Ruijin , Wang Xiaoqin , Weijdegård Birgitta , Norström Anders , Fernandez-Rodriguez Julia , Brännström Mats , Billig Håkan
Published: March 2012

Heterogeneous nuclear ribonucleoproteins (hnRNPs), which are chromatin-associated RNA-binding proteins, participate in mRNA stability, transport, intracellular localization, and translation by acting as transacting factors. Several studies have shown that steroid hormones can regulate hnRNP expression. However, to date, the regulation of hnRNPs and their interactions with steroid hormone signaling in fallopian tubes and endometrium are not fully elucidated. In the present study, we determined whether hnRNP expression is regulated during the menstrual cycle and correlates with estrogen receptor (ER) and progesterone receptor (PR) levels in human fallopian tubes in vivo. Because of the limited availability of human tubal tissues for the research, we also explored the mechanisms of hnRNP regulation in human endometrium in vitro. Fallopian tissue was obtained from patients in the early, late, and postovulatory phases and the midsecretory phase and endometrial tissue from premenopausal and postmenopausal women undergoing hysterectomy. We measured expression of hnRNPs and assessed their intracellular localization and interactions with ERs and PRs. We also determined the effects of human chorionic gonadotropin, 17β-estradiol (E2), and progesterone (P4) on hnRNP expression. In fallopian tubes, mRNA and protein levels of hnRNP A1, AB, D, G, H, and U changed dynamically during ovulation and in the midsecretory phase. In coimmunolocation and coimmunoprecipitation experiments, hnRNPs interacted with each other and with ERs and PRs in fallopian tubes. After treatment with E2 and/or P4 to activate ERs and PRs, hnRNP A1, AB, D, G, and U proteins displayed overlapping but distinct patterns of regulation in the endometrium in vitro. Our findings expand the physiological repertoire of hnRNPs in human fallopian tubes and endometrium and suggest that steroid hormones regulate different hnRNPs directly by interacting with ERs and/or PRs or indirectly by binding other hnRNPs. Both actions may contribute to regulation of gene transcription.
Electrical Properties of a CeO2-Bi2O3Mix System Elaborated at 600°C
Authors: Bourja Lamia , Bakiz Bahcine , Benlhachemi Abdeljalil , Ezahri Mohamed , Villain Sylvie , Favotto Claude , Gavarri Jean-Raymond
Published: March 2012

The electrical conduction of a series of polycristalline [(1−x)CeO2⋅x/2Bi2O3] samples has been analyzed using electrical impedance spectroscopy, in the temperature range 25 to750∘C. Samples have been prepared via a coprecipitation route followed by a pyrolysis process at600∘C. For compositionsx≤0.20, Ce1−xBixO2−x/2solid solutions, with fluorite cubic structure, are obtained. In the composition range0.30≤x≤1, the system is biphasic with coexistence of cubic and tetragonal structures. To interpret the Nyquist representations of electrical analyses, various impedance models including constant phase elements and Warburg impedances have been used. In the biphasic range (0.30≤x≤0.7), the conductivity variation might be related to the increasing fraction of two tetragonal β′and β-Bi2O3phases. The stabilization of the tetragonal phase coexisting with substituted ceria close to compositionx=0.7is associated with a high conduction of the mix system CeO2-Bi2O3.
Full-Length Enrich c-DNA Libraries-Clear Cell-Renal Cell Carcinoma
Authors: Tang Sai-Wen , Lin Jung-Yaw
Published: March 2012

Clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, is characterized by high metastasis potential and strong resistance to traditional therapies, resulting in a poor five-year survival rate of patients. Several therapies targeted to VEGF pathway for advanced RCC have been developed, however, it still needs to discover new therapeutic targets for treating RCC. Genome-wide gene expression analyses have been broadly used to identify unknown molecular mechanisms of cancer progression. Recently, we applied the oligo-capping method to construct the full-length cDNA libraries of ccRCC and adjacent normal kidney, and analyzed the gene expression profiles by high-throughput sequencing. This paper presents a review for recent findings on therapeutic potential of MYC pathway and nicotinamide N-methyltransferase for the treatment of RCC.
Quality of Life and Utility in Patients with Metastatic Soft Tissue and Bone Sarcoma: The Sarcoma Treatment and Burden of Illness in North America and Europe (SABINE) Study
Authors: Reichardt Peter , Leahy Michael , Garcia del Muro Xavier , Ferrari Stefano , Martin Javier , Gelderblom Hans , Wang Jingshu , Krishna Arun , Eriksson Jennifer , Staddon Arthur , Blay Jean-Yves
Published: March 2012

The aim of the study was to assess health-related quality of life (HRQoL) among metastatic soft tissue (mSTS) or bone sarcoma (mBS) patients who had attained a favourable response to chemotherapy. We employed the EORTC QLQ-C30, the 3-item Cancer-Related Symptoms Questionnaire, and the EQ-5D instrument. HRQoL was evaluated overall and by health state in 120 mSTS/mBS patients enrolled in the SABINE study across nine countries in Europe and North America. Utility was estimated from responses to the EQ-5D instrument using UK population-based weights. The mean EQ-5D utility score was 0.69 for the pooled patient sample with little variation across health states. However, patients with progressive disease reported a clinically significant lower utility (0.56). Among disease symptoms, pain and respiratory symptoms are common. This study showed that mSTS/mBS is associated with reduced HRQoL and utility among patients with metastatic disease.
On the Convergence of Mann and Ishikawa Iterative Processes for Asymptotically ϕ‐Strongly Pseudocontractive Mappings
Authors: Wang Xuewu , Marino Giuseppe , Muglia Luigi
Published: March 2012

We prove the equivalence and the strong convergence of (1) the modified Mann iterative process and (2) the modified Ishikawa iterative process for asymptotically ϕ‐strongly pseudocontractive mappings in a uniformly smooth Banach space.
Signalling Pathways Passing Src in Pancreatic Endocrine Tumours: Relevance for Possible Combined Targeted Therapies
Authors: Capurso Gabriele , Di Florio Alessia , Sette Claudio , Delle Fave Gianfranco
Published: March 2012

The most frequent molecular abnormalities in pancreatic endocrine tumours (PETs) are mutations of the MEN1 gene, deregulation of the PI3K/AKT/mTOR signalling pathway and overactivation of growth factors and their receptors, such as the VEGF. On this basis, everolimus (Afinitor®; Novartis) and sunitinib (Sutent®; Pfizer) have both been approved by the FDA for the treatment of progressive, unresectable, locally advanced or metastatic PETs. However, molecular or surrogate markers able to predict the response of PET patients to treatment with these drugs are not available, and cancer cells treated with targeted therapies might develop escape pathways that evoke pro-survival feedback responses. The existence of cross-talk between different molecular pathways in PETs has been poorly investigated. In the present review, we present data supporting an important role for Src family kinases (SFKs) in PETs, together with the recent observation of a novel role for SFK in modulating the mTOR pathway activity. Of note, while treatment with everolimus triggered the activation of a survival response dependent on PI3K/AKT signalling in vitro, the simultaneous inhibition of SFKs blocked the activation of this unwanted escape signal. These studies might set the ground for the investigation of combined treatment of PETs with SFK and mTOR inhibitors.
Central Prolactin Modulates Insulin Sensitivity and Insulin Secretion in Diabetic Rats
Authors: Park Sunmin , Kang Suna , Lee Hye-Won , Ko Byoung Seob
Published: March 2012

Background: Prolactin secretion is self-regulating as it acts upon hypothalamic dopaminergic systems which inhibit prolactin release from the anterior pitutary. Circulating prolactin improves glucose homeostasis by increasing insulin action and secretion, but central prolactin effects on glucose homeostasis have not been examined. Here, we determined that chronic central infusion of prolactin modulates insulin resistance and β-cell function and mass in 90% of pancreatectomized diabetic male rats. Methods: Diabetic rats were divided into three groups according to the dose of intracerebroventricular infusion of prolactin during 4 weeks: (1) low-dose prolactin (Low-PRL; 0.1 µg/h), (2) high-dose prolactin (High-PRL; 1 µg/h) and (3) vehicle only (cerebrospinal fluid). Nondiabetic rats were centrally infused with the vehicle. Results: Chronic intracerebroventricular infusion of Low-PRL lowered body weight and epididymal fat pads by increasing hypothalamic dopamine levels that reduced serum prolactin levels and potentiated leptin signaling. However, High-PRL slightly exacerbated energy dysregulation, decreased hypothalamic dopamine levels, and elevated serum prolactin levels. Both dosages promoted β-cell mass but in a different manner: Low-PRL decreased β-cell apoptosis, whereas High-PRL increased its proliferation. However, only Low-PRL enhanced first-phase insulin secretion and improved insulin sensitivity at a hyperglycemic state in comparison to the control. Low-PRL also increased glucose infusion rates and decreased hepatic glucose output in hyperinsulinemic states, signifying an improvement in hepatic insulin sensitivity. However, High-PRL exacerbated hepatic insulin resistance compared with the control diabetic rats. Conclusions: In contrast to the exacerbation of insulin resistance caused by High-PRL, Low-PRL may improve energy and glucose metabolism by increasing hypothalamic dopamine levels in diabetic rats.
Duration of Targeted Therapy for Metastatic Renal Cell Carcinoma: A Review of Current Practices
Authors: Négrier Sylvie
Published: March 2012

The development of targeted agents has substantially improved clinical outcomes for patients with metastatic renal cell carcinoma. The optimum duration of treatment with these agents is not yet clear, particularly as targeted agents may often result in disease stabilization as well as in tumour response. Some clinicians may choose to switch to an alternative agent in the absence of tumour response or in the event of the occurrence of side effects, which can result in patients moving rapidly through the available treatment options. This review evaluates the duration of treatment observed with targeted agents that are approved for first-line treatment of metastatic renal cell carcinoma and considers the reasons for switching or discontinuing therapy. In addition, practical strategies for achieving optimal treatment duration, through adverse event management, are discussed.
Circulation: Heart Failure
Editors' Picks
Authors: Kociol Robb D.
Published: March 2012

The following are highlights from
Circulation: Heart Failure
's Topic Review. This series summarizes the most important manuscripts, as selected by the editors, that have been published in the
Circulation
portfolio. The objective of this series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the heart failure audience. The studies included in this article represent the most noteworthy research in the areas of pathophysiology and genetics.
Sources of Hospital Variation in Short-Term Readmission Rates After Percutaneous Coronary Intervention
Authors: Yeh Robert W. , Rosenfield Kenneth , Zelevinsky Katya , Mauri Laura , Sakhuja Rahul , Shivapour Daniel M. , Lovett Ann , Weiner Bonnie H. , Jacobs Alice K. , Normand Sharon-Lise T.
Published: March 2012

Background—

Risk-standardized all-cause 30-day readmission rates (RSRRs) after percutaneous coronary intervention (PCI) have been endorsed as a national measure of hospital quality. Little is known about variation in the performance of hospitals on this measure, and whether high hospital rates of readmission after PCI are due to modifiable deficiencies in quality of care has not been assessed.

Methods and Results—

We estimated 30-day, all-cause RSRRs for all nonfederal PCI-performing hospitals in Massachusetts, adjusted for clinical and angiographic variables, between 2005 and 2008. We assessed if differences in race, insurance type, and PCI and post-PCI characteristics, including procedural complications and discharge characteristics, could explain variation between hospitals using nested hierarchical logistic regression models. Of 36 060 patients undergoing PCI at 24 hospitals and surviving to discharge, 4469 (12.4%) were readmitted within 30 days of discharge. Hospital RSRRs ranged from 9.5% to 17.9%, with 8 of 24 hospitals being identified as outliers (4 lower than expected and 4 higher than expected). Differences in race, insurance, PCI, and post-PCI factors accounted for 10.4% of the between-hospital variance in RSRRs.

Conclusions—

We observed wide variation in hospital 30-day all-cause RSRRs after PCI, most of which could not be explained by identifiable differences in procedural and postprocedural factors. A better understanding of etiologies of hospital variation is necessary to determine whether this measure is an actionable assessment of hospital quality, and, if so, how hospitals might improve their performance.
Distinguishing Effects of Game Framing and Journalistic Adjudication on Cynicism and Epistemic Political Efficacy
Authors: Pingree Raymond J. , Hill Megan , McLeod Douglas M.
Published: March 2012

An online experiment tested the influence of “he said/she said” coverage versus active adjudication of factual disputes, as well as strategy versus policy framing in postdebate news coverage. Adjudication in policy-framed stories increased epistemic political efficacy (EPE), a measure of confidence in one’s own ability to determine the truth in politics. However, adjudicated policy stories also elicited greater cynicism than passive policy framing. This suggests a caveat for the spiral of cynicism, calling into question its assumption that all policy framing behaves similarly in reducing cynicism. Results also provide several forms of evidence that effects of adjudication on EPE differ from spiral of cynicism effects while further validating the EPE construct as distinct from the reverse of political cynicism. Adjudication also positively affected evaluations of the coverage as interesting and informative.
Behind the Veil of Juror Decision Making
Authors: Maeder Evelyn , Dempsey Julie , Pozzulo Joanna
Published: March 2012

Recent case law has considered whether a Muslim woman who wishes to appear in court should be allowed to testify wearing a veil that covers part of her face (e.g., Muhammad v. Paruk, 2008, in the United States, R. v. N.S., 2009, in Canada). The current research sought to test the influence of a victim’s wearing of a veil while testifying on juror decision making in a sexual assault trial. In addition, the study tested for effects of defendant race using Middle Eastern and Caucasian as the target races, given that there is a paucity of research comparing these races in the juror decision-making literature. Results demonstrated that contrary to hypotheses, jurors were more convinced of the defendant’s guilt when the victim was wearing a burqa or hijab to testify than when she testified wearing no veil. Defendant race did not have an effect on any of the dependent variables in this research; however, mock juror gender was found to be influential. Potential reasons for these findings and directions for future research are discussed.
Rapid Enrichment of Cell Phospholipids in Long‐Chain Polyunsaturated ω‐3 Fatty Acids After a Bolus Intravenous Injection of a Medium‐Chain Triacylglycerol
Authors: Carpentier Yvon A. , Portois Laurence , Malaisse Willy J.
Published: March 2012

The present review aims at highlighting the use of a recently developed medium‐chain triacylglycerol:fish oil (MCT:FO) emulsion for the rapid and sustained enrichment of long‐chain polyunsaturated ω‐3 fatty acids in cell phospholipids. Preclinical in vitro, in vivo, and ex vivo experiments are briefly considered with emphasis on the changes in the fatty acid pattern of cell phospholipids in several organs, the partial correction of liver steatosis, and the cardiovascular modification of cationic and functional variables observed in ω‐3‐depleted rats examined 60–120 minutes after a bolus intravenous (IV) injection (1.0 mL) of the MCT:FO emulsion. The clinical findings collected in healthy male volunteers before or after the bolus IV injection (50.0 mL) of either the MCT:FO emulsion or a control medium‐chain triacylglycerol:long‐chain triacylglycerol emulsion are also reviewed, with emphasis on the rapid (within 60 minutes) and sustained (up to 2–3 days) enrichment of platelet and white blood cell phospholipids in long‐chain polyunsaturated ω‐3 fatty acids and hemostatic safety of the present procedure proposed as a tool for the rapid prevention or correction of metabolic and functional disturbances in humans with a relative deficiency in such ω‐3 fatty acids.
Comparative Analysis of Tumor‐Infiltrating Lymphocytes in a Syngeneic Mouse Model of Oral Cancer
Authors: Judd Nancy P. , Allen Clint T. , Winkler Ashley E. , Uppaluri Ravindra
Published: March 2012

Objective

To perform a comparative analysis of infiltrating immune cells in a newly developed C57BL/6 background syngeneic transplantable mouse oral cancer (MOC) model.

Study Design/Setting

Scientific study in an academic medical center.

Methods

Use of carcinogen‐induced tumorigenesis, tissue culture, cell line transplantation, and flow cytometric analysis techniques.

Results

Previously, the authors established a series of cell line models that displayed dichotomous growth phenotypes when transplanted into immunocompetent mice. They now show that the indolent growth pattern of the MOC1‐generated tumors is associated with increased baseline and inducible major histocompatibility complex class I expression and increased CD8+ T‐cell infiltration into the tumor microenvironment. Conversely, the aggressive and metastatic pattern of MOC2‐generated tumors has decreased basal and inducible class I expression and is associated with FOXP3+CD4+ regulatory T‐cell infiltration. Delayed primary tumor growth after targeted monoclonal antibody therapy of these FOXP3+ regulatory cells further suggests that these immune cells contribute to the aggressive phenotype of MOC2.

Conclusion

These data validate that key infiltrating immune cells identified here parallel findings in human head and neck cancer, making this newly developed syngeneic model a critical platform for the continued dissection of tumor‐host interactions in head and neck cancer.
A Reexamination of Sex Differences in Sexuality
Authors: Schmitt David P. , Jonason Peter K. , Byerley Garrett J. , Flores Sandy D. , Illbeck Brittany E. , O’Leary Kimberly N. , Qudrat Ayesha
Published: March 2012

Recent evidence seems to call into question long-established findings of sex differences in sexuality, such as differences in mate preferences and desires for casual sex. In this article, we place new findings in a broader evidence-based context and show that they confirm previous perspectives on human mating. A wealth of evidence from real-world studies of actual mate choice and marital dynamics supports evolutionary mate-preference predictions. Converging evidence from patterns of extradyadic sex, mate poaching, sexual fantasies, pornography consumption, postcoital regret, sociosexual attitudes, and willingness to engage in casual sex supports the view that men and women have distinct short-term mating psychologies. This article highlights the fact that good science requires a constant re-evaluation of old truths and the proper placement of new studies in broad evidentiary contexts.
‘Critique is impossible without moves’: An interview of Kojin Karatani by Joel Wainwright
Authors: Karatani Kojin , Wainwright Joel
Published: March 2012

In this dialogue, geographer Joel Wainwright interviews the celebrated Marxist philosopher, Kojin Karatani. Their wide-ranging discussion examines key concepts by a series of philosophers – especially Kant, Marx, Hegel and Derrida – through an analysis of several core geographical concerns: the spatial organization of global capitalism, the formation of empires and territorial nation states, the current economic crisis, and more. The interview concludes with a discussion of the conditions of possibility of transcending the dominant social formation (i.e. capital-nation-state).
Identification of Iopanoic Acid as Substrate of Type 1 Deiodinase by a Novel Nonradioactive Iodide-Release Assay
Authors: Renko Kostja , Hoefig Carolin S. , Hiller Franziska , Schomburg Lutz , Köhrle Josef
Published: March 2012

Enzymatic 5'- and 5-deiodination are key reactions for local and systemic activation and inactivation of iodothyronines and thyronamines. Expression of the three deiodinase (DIO) isoenzymes is regulated by a number of parameters, including thyroid status, genotype, micronutrient availability, and disease-related signaling. In addition, DIO are potential targets of pharmacological as well as environmentally derived substances, which might affect their enzymatic activity (endocrine disruptors). With the classical DIO activity assay, testing depends on the availability of radioactively labeled substrates (e.g. 125I-rT3) to monitor the release of radioactive iodide. Recently, liquid chromatography-tandem mass spectrometry was described as an alternative method apparently resolving this limitation. However, it has a high demand in technical equipment and analytical routine and is limited in sample number by considerable measuring time. We therefore combined the classical deiodination assay with an easily accessible photometric method taking advantage of the Sandell-Kolthoff reaction for measuring iodide release. In brief, iodine works as a catalyst within this redox reaction between Ce4+ and As3+ leading to an acceleration of destaining. Furthermore, the protocol was adapted to minimize handling effort and time consumption. Because this method is not dependent on radioactivity, it expands the substrate spectrum of the classical method. Suitability of this assay was tested with tissue samples from animal experiments (hepatic Dio1 activity in hypo- and hyperthyroid mice) and established DIO inhibitors. As a new but not unexpected finding, the alleged inhibitor iopanoic acid turned out to be a DIO substrate. This finding was confirmed by liquid chromatography-tandem mass spectrometry, and its potential clinical impact requires further studies.
Honey bee drones maintain humoral immune competence throughout all life stages in the absence of vitellogenin production
Authors: Gätschenberger Heike , Gimple Olaf , Tautz Jürgen , Beier Hildburg
Published: March 2012

Drones are haploid male individuals whose major social function in honey bee colonies is to produce sperm and mate with a queen. In spite of their limited tasks, the vitality of drones is of utmost importance for the next generation. The immune competence of drones – as compared to worker bees – is largely unexplored. Hence, we studied humoral and cellular immune reactions of in vitro reared drone larvae and adult drones of different age upon artificial bacterial infection. Haemolymph samples were collected after aseptic and septic injury and subsequently employed for (1) the identification of immune-responsive peptides and/or proteins by qualitative proteomic analyses in combination with mass spectrometry and (2) the detection of antimicrobial activity by inhibition-zone assays. Drone larvae and adult drones responded with a strong humoral immune reaction upon bacterial challenge, as validated by the expression of small antimicrobial peptides. Young adult drones exhibited a broader spectrum of defence reactions than drone larvae. Distinct polypeptides including peptidoglycan recognition protein-S2 and lysozyme 2 were upregulated in immunized adult drones. Moreover, a pronounced nodulation reaction was observed in young drones upon bacterial challenge. Prophenoloxidase zymogen is present at an almost constant level in non-infected adult drones throughout the entire lifespan. All observed immune reactions in drones were expressed in the absence of significant amounts of vitellogenin. We conclude that drones – like worker bees – have the potential to activate multiple elements of the innate immune response.
Asymmetric First-Price Auctions—A Dynamical-Systems Approach
Authors: Fibich Gadi , Gavish Nir
Published: March 2012

We introduce a new approach for analysis and numerical simulations of asymmetric first-price auctions, which is based on dynamical systems. We apply this approach to asymmetric auctions in which players' valuations are power-law distributed. We utilize a dynamical-systems formulation to provide a proof of the existence and uniqueness of the equilibrium strategies in the cases of two coalitions and of two types of players. In the case of n different players, the singular point of the original system at b = 0 corresponds to a saddle point of the dynamical system with n − 1 admissible directions. This insight enables us to use forward solutions in the analysis and in the numerical simulations, in contrast with previous analytic and numerical studies that used backward solutions. The dynamical-systems approach provides an intuitive explanation for why the standard backward-shooting method for computing the equilibrium strategies is inherently unstable, and enables us to devise a stable forward-shooting method. In particular, in the case of two types of players, this method is extremely simple, as it does not require any shooting.
Unique Minimal Liftings for Simplicial Polytopes
Authors: Basu Amitabh , Cornuéjols Gérard , Köppe Matthias
Published: March 2012

For a minimal inequality derived from a maximal lattice-free simplicial polytope in ℝn, we investigate the region where minimal liftings are uniquely defined, and we characterize when this region covers ℝn. We then use this characterization to show that a minimal inequality derived from a maximal lattice-free simplex in ℝn with exactly one lattice point in the relative interior of each facet has a unique minimal lifting if and only if all the vertices of the simplex are lattice points.