bluuebunny/crossref_metadata_2025 huggingface dataset:
The need for and provision of intrathecal baclofen therapy for the management of spasticity in England: an assessment of the Hospital Episode Statistics database
Authors: Narendran Rajesh C , Duarte Rui V , Valyi Andrea , Eldabe Sam
Published: July 2015

Objectives

The aim of this study was to evaluate changes in the uptake of intrathecal baclofen (ITB) following commissioning of this therapy by the National Health Service (NHS) England in April 2013. The specific objectives of this study were: (i) to explore the gap between the need for and the actual provision of ITB services; and (ii) to compare England figures with other European countries with comparable data available.

Setting

Data for ITB -related procedures were obtained from the Hospital Episode Statistics (HES) database from 2009/2010 to 2013/2014.

Participants

Patients receiving ITB for the management of spasticity.

Results

The available data for implantation of ITB from 2009/2010 to 2013/2014 for the treatment of spasticity due to varied aetiologies show that there has not been an increase in uptake of this therapy. The estimated need for this treatment based on the incidence and prevalence of conditions susceptible to ITB therapy is between 4.6 and 5.7 per million population. Our analysis of the data available from the HES database showed that the actual number of implants is around 3.0 per million population. The same period 2009–2014 has seen an increase in the delivery of other neuromodulation techniques including spinal cord stimulation, deep brain stimulation and sacral nerve stimulation.

Conclusions

There is a considerable gap between the need for and provision of ITB figures nationally. Additionally, within the same area, we have observed important differences in the ITB service delivery between the various trusts. The reasons for this can be multifactorial, including individual experience and opinions, organisational structures, resource and financial limitations. Further research analysing the efficacy and cost-effectiveness of this treatment in the UK might inform the development of Technology Appraisal Guidance for ITB, potentially leading to an improvement in service provision.
The correlation between blood pressure and kidney function decline in older people: a registry-based cohort study
Authors: Vaes Bert , Beke Emilie , Truyers Carla , Elli Steven , Buntinx Frank , Verbakel Jan Y , Goderis Geert , Van Pottelbergh Gijs
Published: July 2015

Objectives

To examine the relation between static and dynamic blood pressure (BP) measurements and the evolution of kidney function in older people, adjusted for the presence of multimorbidity.

Design

Retrospective cohort study during a 10-year time interval (2002–2012) in three age strata of patients aged 60 and older.

Setting

Primary care registration network with 97 general practitioners working in 55 practices regularly submitting collected patient data.

Participants

All patients with at least one BP measurement in 2002 and at least four serum creatine measurements after 2002 (n=8636). A modified Charlson Comorbidity Index (mCCI) at baseline was registered. Change in systolic and diastolic BP (DBP) and pulse pressure (PP) from 2002 onwards was calculated. The relation between kidney function evolution and baseline BP and change in BP was examined using linear and logistic regression analysis.

Main outcome measures

The slope of the estimated glomerular filtration rate (eGFR, MDRD, Modification of Diet in Renal Disease equation) was calculated by the ordinal least square method. A rapid annual decline of kidney function was defined as ≥3 mL/min/1.73 m2/year.

Results

Rapid annual decline of kidney function occurred in 1130 patients (13.1%). High baseline systolic BP (SBP) and PP predicted kidney function decline in participants aged 60–79 years. No correlation between baseline BP and kidney function decline was found in participants aged 80 years and older. An annual decline of ≥1 mm Hg in SBP and PP was a strong risk factor for a rapid annual kidney function decline in all age strata, independent of baseline BP and mCCI. A decline in DBP as also a strong independent predictor in participants aged 60–79 years.

Conclusions

The present study identified a decline in BP over time as a strong risk factor for kidney function decline in all age strata, adjusted for mCCI and baseline kidney function and BP.
How can healthcare standards be standardised?
Authors: Shaw Charles D
Published: July 2015

International travel, medical tourism and trade have created a demand for reliable assessment of healthcare provision across borders, and for information which is accessible to patients, insurers and referring institutions. External assessment schemes for healthcare providers may be clustered into three types: statutory regulation and institutional licensing, International Standardization Organisation certification, and voluntary systems such as peer review and healthcare accreditation. Increasing complexity of healthcare provision, pressures for public accountability and expectations of professional self-governance place a burden on the inspectors and the inspected. If only to contain costs of external assessment and to increase access to reliable information for patients and insurers, the three approaches must work together rather than compete. This paper summarises the origins, aims, authority and methods of the three general models, describing current pressures and opportunities for convergence (between systems and across borders) in the UK and in Europe.
Updated reduced CMB data and constraints on cosmological parameters
Authors: Cai Rong-Gen , Guo Zong-Kuan , Tang Bo
Published: July 2015

We obtain the reduced CMB data {lA, R, z∗} from WMAP9, WMAP9+BKP, Planck+WP and Planck+WP+BKP for the ΛCDM and wCDM models with or without spatial curvature. We then use these reduced CMB data in combination with low-redshift observations to put constraints on cosmological parameters. We find that including BKP results in a higher value of the Hubble constant especially when the equation of state (EOS) of dark energy and curvature are allowed to vary. For the ΛCDM model with curvature, the estimate of the Hubble constant with Planck+WP+Lensing is inconsistent with the one derived from Planck+WP+BKP at about 1.2σ confidence level (CL).
The little sibling of the big rip singularity
Authors: Bouhmadi-López Mariam , Errahmani Ahmed , Martín-Moruno Prado , Ouali Taoufik , Tavakoli Yaser
Published: July 2015

In this paper, we present a new cosmological event, which we named the little sibling of the big rip. This event is much smoother than the big rip singularity. When the little sibling of the big rip is reached, the Hubble rate and the scale factor blow up, but the cosmic derivative of the Hubble rate does not. This abrupt event takes place at an infinite cosmic time where the scalar curvature explodes. We show that a doomsday à la little sibling of the big rip is compatible with an accelerating universe, indeed at present it would mimic perfectly a ΛCDM scenario. It turns out that, even though the event seems to be harmless as it takes place in the infinite future, the bound structures in the universe would be unavoidably destroyed on a finite cosmic time from now. The model can be motivated by considering that the weak energy condition should not be strongly violated in our universe, and it could give us some hints about the status of recently formulated nonlinear energy conditions.
Effects of Water Supply on Labor Demand and Agricultural Production in California's San Joaquin Valley
Authors: Speir Cameron , Mamula Aaron , Ladd Daniel
Published: July 2015

We estimate the effect of changes in water deliveries from large projects on agricultural production. We estimate a region-scale, multi-output production model of the San Joaquin Valley of California using observed historical data. The model incorporates seven crop outputs and the labor input as functions of project water supply, groundwater pumping price, other surface water sources, wages, and crop prices. We find that: (1) reduced irrigation water supply reduces the demand for farm labor and the production of some crops, (2) regional production mix tends to shift towards cotton when water supply is high and (3) some structural change has occurred over the course of our 22 year study period, with production of annual crops becoming more sensitive to changes in project water supply and labor becoming less sensitive to local surface water conditions.
Household Adoption of Water Conservation and Resilience Under Drought: The Case of Oklahoma City
Authors: Boyer Tracy A. , Kanza Patrick , Ghimire Monika , Moss Justin Q.
Published: July 2015

Drought response management by utilities in the semi-arid Midwest has been less common outside of Texas than in the Western United States. In response to Oklahoma's unprecedented drought of 2012, Oklahoma City's Water Utilities Trust sought to identify the potential for targeting outdoor conservation education and other incentives such as rebates for low-flow toilets and soil moisture sensors for irrigation systems. This research uses a unique dataset that combines actual household consumption data and county assessor's data of house market value and characteristics with a survey of household conservation adoption of indoor and outdoor water conservation methods. Increased education, age, and income all were found to positively affect indoor and outdoor conservation adoption. Surprisingly neither higher summer consumption during severe drought, nor the perception of prolonged drought increased outdoor conservation adoption, but owning previously conserving Bermuda lawn did increase adoption. However, indoor adoption was higher for homeowners and those who expected prolonged drought. Results suggest that incentives should be targeted at low and average income homeowners and that education regarding the benefits of outdoor conservation should be targeted at all homeowners regarding the higher marginal benefit of seasonal reductions in outdoor watering.
Option prices and model-free measurement of implied herd behavior in stock markets
Authors: Linders Daniël , Dhaene Jan , Schoutens Wim
Published: July 2015

In this paper, we introduce two classes of indices which can be used to measure the market perception concerning the degree of dependency that exists between a set of random variables, representing different stock prices at a fixed future date. The construction of these measures is based on the theory of comonotonicity. Both types of herd behavior indices are model-free and risk-neutral, derived from available option data. Depending on its particular definition, each index represents a particular aspect of the market sentiment concerning future co-movement of the underlying stock prices.
Ionization Mechanism of Matrix-Assisted Laser Desorption/Ionization
Authors: Lu I-Chung , Lee Chuping , Lee Yuan-Tseh , Ni Chi-Kung
Published: July 2015

In past studies, mistakes in determining the ionization mechanism in matrix-assisted laser desorption/ionization (MALDI) were made because an inappropriate ion-to-neutral ratio was used. The ion-to-neutral ratio of the analyte differs substantially from that of the matrix in MALDI. However, these ratios were not carefully distinguished in previous studies. We begin by describing the properties of ion-to-neutral ratios and reviews early experimental measurements. A discussion of the errors committed in previous theoretical studies and a comparison of recent experimental measurements follow. We then describe a thermal proton transfer model and demonstrate how the model appropriately describes ion-to-neutral ratios and the total ion intensity. Arguments raised to challenge thermal ionization are then discussed. We demonstrate how none of the arguments are valid before concluding that thermal proton transfer must play a crucial role in the ionization process of MALDI.
Virtuality
Authors: Nardi Bonnie
Published: July 2015

This review examines studies of the affordances of digital technologies that produce virtuality. What we can call a “technological turn” in the literature considers technology a first-order analytical object rather than blackboxing it or subsuming it under social process. J.J. Gibson's original concept of affordance is explained, as well as its evolution to a concept consonant with anthropology's concerns. The review probes studies of political activism, work, and play. It comments on how virtuality affects anthropology as a discipline.
Materials Data Science: Current Status and Future Outlook
Authors: Kalidindi Surya R. , De Graef Marc
Published: July 2015

The field of materials science and engineering is on the cusp of a digital data revolution. After reviewing the nature of data science and Big Data, we discuss the features of materials data that distinguish them from data in other fields. We introduce the concept of process-structure-property (PSP) linkages and illustrate how the determination of PSPs is one of the main objectives of materials data science. Then we review a selection of materials databases, as well as important aspects of materials data management, such as storage hardware, archiving strategies, and data access strategies. We introduce the emerging field of materials data analytics, which focuses on data-driven approaches to extract and curate materials knowledge from available data sets. The critical need for materials e-collaboration platforms is highlighted, and we conclude the article with a number of suggestions regarding the near-term future of the materials data science field.
Polymer-Based Dielectrics with High Energy Storage Density
Authors: Chen Qin , Shen Yang , Zhang Shihai , Zhang Q.M.
Published: July 2015

Polymer film capacitors are critical components in many high-power electrical systems. Because of the low energy density of conventional polymer dielectrics, these capacitors currently occupy significant volume in the entire electrical system. This article reviews recent progress made in the development of polymer dielectrics with high energy storage density, which can potentially lead to significant weight and volume reduction in polymer film capacitors. The increase in energy density is achieved through two approaches, namely (a) the development of novel polymers with high electric polarization and optimized dielectric responses and (b) the development of nanocomposites containing polymer matrixes with high breakdown strength and inorganic nanofillers with high polarization. Promising progress has been made through both strategies, resulting in a maximum energy density of >30 J/cm3, which is at least 5 times higher than those of conventional polymer dielectrics. The state-of-the-art manufacturing method for low-cost, high-throughput production of polymer films is also reviewed.
Agricultural Research by the Private Sector
Authors: Pray Carl E. , Fuglie Keith O.
Published: July 2015

The private sector has assumed a larger role in developing improved technology for food and agriculture, with private agricultural R&D spending growing faster than public agricultural R&D spending over the past several decades. Major drivers have been new commercial opportunities afforded by scientific advances and liberalization of agricultural input markets. Along with rising private R&D investment, agricultural input industries have undergone significant structural changes. These developments have been pronounced in both high-income and developing countries. The rising importance of private R&D, however, does not imply a diminished role of the public sector, as most empirical evidence points to complementarities between public and private agricultural R&D.
Glucose intolerance and pancreatic β-cell dysfunction in the anorecticanx/anxmouse
Authors: Lindfors Charlotte , Katz Abram , Selander Lars , Johansen Jeanette E. , Marconi Giulia , Schalling Martin , Hökfelt Tomas , Berggren Per-Olof , Zaitsev Sergei , Nilsson Ida A. K.
Published: July 2015

Inflammation and impaired mitochondrial oxidative phosphorylation are considered key players in the development of several metabolic disorders, including diabetes. We have previously shown inflammation and mitochondrial dysfunction in the hypothalamus of an animal model for anorexia, the anx/ anx mouse. Moreover, increased incidence of eating disorders, e.g., anorexia nervosa, has been observed in diabetic individuals. In the present investigation we evaluated whether impaired mitochondrial phosphorylation and inflammation also occur in endocrine pancreas of anorectic mice, and if glucose homeostasis is disturbed. We show that anx/ anx mice exhibit marked glucose intolerance associated with reduced insulin release following an intraperitoneal injection of glucose. In contrast, insulin release from isolated anx/ anx islets is increased after stimulation with glucose or KCl. In isolated anx/ anx islets there is a strong downregulation of the mitochondrial complex I (CI) assembly factor, NADH dehydrogenase (ubiquinone) 1α subcomplex, assembly factor 1 ( Ndufaf1), and a reduced CI activity. In addition, we show elevated concentrations of free fatty acids (FFAs) in anx/ anx serum and increased macrophage infiltration (indicative of inflammation) in anx/ anx islets. However, isolated islets from anx/ anx mice cultured in the absence of FFAs do not exhibit increased inflammation. We conclude that the phenotype of the endocrine pancreas of the anx/ anx mouse is characterized by increased levels of circulating FFAs, as well as inflammation, which can inhibit insulin secretion in vivo. The anx/ anx mouse may represent a useful tool for studying molecular mechanisms underlying the association between diabetes and eating disorders.
Interactions between HIF-1α and AMPK in the regulation of cellular hypoxia adaptation in chronic kidney disease
Authors: Li Hui , Satriano Joseph , Thomas Joanna L. , Miyamoto Satoshi , Sharma Kumar , Pastor-Soler Núria M. , Hallows Kenneth R. , Singh Prabhleen
Published: July 2015

Renal hypoxia contributes to chronic kidney disease (CKD) progression, as validated in experimental and human CKD. In the early stages, increased oxygen consumption causes oxygen demand/supply mismatch, leading to hypoxia. Hence, early targeting of the determinants and regulators of oxygen consumption in CKD may alter the disease course before permanent damage ensues. Here, we focus on hypoxia inducible factor-1α (HIF-1α) and AMP-activated protein kinase (AMPK) and on the mechanisms by which they may facilitate cellular hypoxia adaptation. We found that HIF-1α activation in the subtotal nephrectomy (STN) model of CKD limits protein synthesis, inhibits apoptosis, and activates autophagy, presumably for improved cell survival. AMPK activation was diminished in the STN kidney and was remarkably restored by HIF-1α activation, demonstrating a novel role for HIF-1α in the regulation of AMPK activity. We also investigated the independent and combined effects of HIF-1α and AMPK on cell survival and death pathways by utilizing pharmacological and knockdown approaches in cell culture models. We found that the effect of HIF-1α activation on autophagy is independent of AMPK, but on apoptosis it is partially AMPK dependent. The effects of HIF-1α and AMPK activation on inhibiting protein synthesis via the mTOR pathway appear to be additive. These various effects were also observed under hypoxic conditions. In conclusion, HIF-1α and AMPK appear to be linked at a molecular level and may act as components of a concerted cellular response to hypoxic stress in the pathophysiology of CKD.
Putting the Squeeze on Airway Epithelia
Authors: Park Jin-Ah , Fredberg Jeffrey J. , Drazen Jeffrey M.
Published: July 2015

Asthma is characterized by chronic inflammation, airway hyperresponsiveness, and progressive airway remodeling. The airway epithelium is known to play a critical role in the initiation and perpetuation of these processes. Here, we review how excessive epithelial stress generated by bronchoconstriction is sufficient to induce airway remodeling, even in the absence of inflammatory cells.
Humans In Hypoxia: A Conspiracy Of Maladaptation?!
Authors: Dempsey Jerome A. , Morgan Barbara J.
Published: July 2015

We address adaptive vs. maladaptive responses to hypoxemia in healthy humans and hypoxic-tolerant species during wakefulness, sleep, and exercise. Types of hypoxemia discussed include short-term and life-long residence at high altitudes, the intermittent hypoxemia attending sleep apnea, or training regimens prescribed for endurance athletes. We propose that hypoxia presents an insult to O2 transport, which is poorly tolerated in most humans because of the physiological cost.
Some Identities Involving the Derivative of the First Kind Chebyshev Polynomials
Authors: Wang Tingting , Zhang Han
Published: July 2015

We use the combinatorial method and algebraic manipulations to obtain several interesting identities involving the power sums of the derivative of the first kind Chebyshev polynomials. This solved an open problem proposed by Li (2015).
Are Aortic Stent Grafts Safe in Pregnancy?
Authors: Khandanpour Nader , Mehta Tapan A. , Adiseshiah M. , Meyer Felicity J.
Published: July 2015

Aortic stent grafts are increasingly used to treat aortic aneurysms and also other aortic pathologies. The safety of aortic stent grafts in pregnancy has never been studied or reported. We report on two cases of aortic stent grafts in pregnant women and discuss the effect of pregnancy on these aortic stent grafts.
Evaluating pH in the Extracellular Tumor Microenvironment Using CEST MRI and Other Imaging Methods
Authors: Chen Liu Qi , Pagel Mark D.
Published: July 2015

Tumor acidosis is a consequence of altered metabolism, which can lead to chemoresistance and can be a target of alkalinizing therapies. Noninvasive measurements of the extracellular pH (pHe) of the tumor microenvironment can improve diagnoses and treatment decisions. A variety of noninvasive imaging methods have been developed for measuring tumor pHe. This review provides a detailed description of the advantages and limitations of each method, providing many examples from previous research reports. A substantial emphasis is placed on methods that use MR spectroscopy and MR imaging, including recently developed methods that use chemical exchange saturation transfer MRI that combines some advantages of MR spectroscopy and imaging. Together, this review provides a comprehensive overview of methods for measuring tumor pHe, which may facilitate additional creative approaches in this research field.
The Influence of Thermal Conditions on V2O5 Nanostructures Prepared by Sol‐Gel Method
Authors: Prześniak-Welenc M. , Łapiński M. , Lewandowski T. , Kościelska B. , Wicikowski L. , Sadowski W.
Published: July 2015

This work presents the result of structure investigations of V2O5 nanorods grown from thin films and powders prepared by sol‐gel method. To examine the best temperature of nanorods crystallization, thin films deposited by spin‐coating method on quartz glass or silicon substrates and bulk xerogel powders were annealed at various temperatures ranging from 100°C to 600°C. The structure of the samples was characterized by X‐ray diffraction method (XRD), scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and mass spectroscopy (MS). The rod‐like structure of V2O5 was obtained at 600°C on both quartz glass and silicon substrates and also from the bulk xerogel. The growth process and the effect of annealing treatment on the nanostructure are briefly discussed.
Neonatal Acute Megakaryoblastic Leukemia Presenting with Leukemia Cutis and Multiple Intracranial Lesions Successfully Treated with Unrelated Cord Blood Transplantation
Authors: Tsujimoto Hiroshi , Kounami Shinji , Mitani Yasuyuki , Watanabe Takashi , Takifuji Katsunari
Published: July 2015

Neonatal acute megakaryoblastic leukemia (AMKL) without Down syndrome (DS) is an extremely rare disorder. We report of a one-day-old male infant without DS who developed AMKL with leukemia cutis and right facial nerve palsy. Magnetic resonance imaging of the patient’s brain revealed multiple intracranial tumors. A biopsy specimen of the skin lesion was suggestive of AMKL, but the bone marrow leukemic cells were less than 5% of the marrow nucleated cells. The skin and intracranial lesions had spontaneously regressed within one and a half months, but the patient’s anemia and thrombocytopenia gradually worsened and the leukemic cells in the bone marrow gradually increased to more than 20% of the nucleated cells. In addition, multiple intracranial lesions reappeared at 72 days of life. We diagnosed the patient with AMKL, and chemotherapy followed by unrelated cord blood transplantation after a reduced-intensity conditioning regimen resulted in sustained complete remission. At present, the patient is well, and he has demonstrated normal development for five years.
Inverse Problems via the “Generalized Collage Theorem” for Vector-Valued Lax-Milgram-Based Variational Problems
Authors: Kunze H. , La Torre D. , Levere K. , Ruiz Galán M.
Published: July 2015

We present an extended version of the Generalized Collage Theorem to deal with inverse problems for vector-valued Lax-Milgram systems. Numerical examples show how the method works in practical cases.
Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism
Authors: Ilias Chatziioannidis , Evgenia Babatseva , Aikaterini Patsatsi , Asimina Galli-Tsinopoulou , Constantina Sarri , Maria Lithoxopoulou , George Mitsiakos , Paraskevi Karagianni , Christos Tsakalidis , Zissis Mamuris , Nikolaos Nikolaidis
Published: July 2015

Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH) deficiency. DNA molecular analysis in theSPINK5gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications.
Synthesis of Inorganic Nanocomposites by Selective Introduction of Metal Complexes into a Self‐Assembled Block Copolymer Template
Authors: Wakayama Hiroaki , Yonekura Hirotaka
Published: July 2015

Inorganic nanocomposites have characteristic structures that feature expanded interfaces, quantum effects, and resistance to crack propagation. These structures are promising for the improvement of many materials including thermoelectric materials, photocatalysts, and structural materials. Precise control of the inorganic nanocomposites’ morphology, size, and chemical composition is very important for these applications. Here, we present a novel fabrication method to control the structures of inorganic nanocomposites by means of a self‐assembled block copolymer template. Different metal complexes were selectively introduced into specific polymer blocks of the block copolymer, and subsequent removal of the block copolymer template by oxygen plasma treatment produced hexagonally packed porous structures. In contrast, calcination removal of the block copolymer template yielded nanocomposites consisting of metallic spheres in a matrix of a metal oxide. These results demonstrate that different nanostructures can be created by selective use of processes to remove the block copolymer templates. The simple process of first mixing block copolymers and magnetic nanomaterial precursors and then subsequently removing the block copolymer template enables structural control of magnetic nanomaterials, which will facilitate their applicability in patterned media, including next‐generation perpendicular magnetic recording media.
Critical Factors Inhibiting Performance of Small- and Medium-Scale Contractors in Sub-Saharan Region: A Case for Malawi
Authors: Kulemeka Paul John , Kululanga Grant , Morton Danny
Published: July 2015

The construction industry is dominated by small- and medium-scale contractors (SMCs) who face an emerging trend of unique challenges in the implementation of projects. The study was aimed at examining inhibiting factors that influence performance of SMCs in terms of “quality of work,” “tender estimation,” “tender preparation,” and “timely completion of construction projects” in Malawi. A survey questionnaire was administered to 370 players in the construction industry which included public sector clients, contractors, consultants, and construction resource trainers in order to elicit data from 118 variables that were identified through a careful literature review. The inhibiting factors were generally dominated by economic issues, which was an emerging trend to what has been previously reported in the sub-Saharan region. The first highest ranked inhibiting factors were high lending interest regimes offered by financial institutions; stringent conditions to access capital; fluctuation of currency; stringent requirements for obtaining bonds; and high taxes. The research lays the foundation for further understanding of inhibitors on performance of SMCs in an evolving world which is being impacted by global factors and punctuated by sudden changes.
Clinical, Psychopathological, and Personality Characteristics Associated with ADHD among Individuals Seeking Treatment for Gambling Disorder
Authors: Aymamí N. , Jiménez-Murcia S. , Granero R. , Ramos-Quiroga J. A. , Fernández-Aranda F. , Claes L. , Sauvaget A. , Grall-Bronnec M. , Gómez-Peña M. , Savvidou L. G. , Fagundo A. B. , del Pino-Gutierrez A. , Moragas L. , Casas M. , Penelo E. , Menchón J. M.
Published: July 2015

Objectives. (1) To assess the current presence of ADHD symptoms among patients seeking treatment for gambling disorder; (2) to explore clinical and sociodemographic differences between patients who score high and low on the measure of ADHD symptoms; (3) to analyze whether the presence of ADHD symptoms is associated with more severe psychopathology and with specific personality traits; (4) to analyze the mediating role of ADHD symptoms in the relationship between novelty seeking and gambling severity.Method. A total of 354 consecutive patients were administered an extensive battery assessing gambling behavior, psychopathology, and personality traits.Results. Male and female gamblers did not differ significantly in their mean scores on the ADHD measure. However, younger participants aged 18–35 scored higher. Higher ADHD scores were also associated with greater severity of gambling disorder and more general psychopathology. Regarding personality traits, high persistence and self-directedness were negatively related to ADHD scores, while in women alone a positive correlation was found between ADHD scores and scores on harm avoidance and self-transcendence.Conclusion. The presence of ADHD symptoms in both male and female gambling disorder patients may act as an indicator of the severity of gambling, general psychopathology, and dysfunctional personality traits.
Structural Properties of the Unobservable Subspace
Authors: Mulero Martínez Juan Ignacio , Baños Alfonso
Published: July 2015

The structural properties of the unobservable subspace are explored. In particular the canonical decomposition of the unobservable subspace as a direct sum of cyclic subspaces as well as the conditions for this subspace to be spectral for the system matrix is studied. These properties are applied to simple input-simple output (SISO) feedback systems by connecting the spectral decomposition of the unobservable subspace to the total cancellation of unobservable modes in the compensator with multiple transmission zeros in the plant.
IL6/JAK1/STAT3 Signaling Blockade in Endometrial Cancer Affects the ALDHhi/CD126+ Stem-like Component and Reduces Tumor Burden
Authors: van der Zee Marten , Sacchetti Andrea , Cansoy Medine , Joosten Rosalie , Teeuwssen Miriam , Heijmans-Antonissen Claudia , Ewing-Graham Patricia C. , Burger Curt W. , Blok Leen J. , Fodde Riccardo
Published: July 2015

Cancer stem–like cells (CSC) may be critical to maintain the malignant behavior of solid and hematopoietic cancers. Recently, patients with endometrial cancer whose tumors expressed high levels of aldehyde dehydrogenase (ALDH), a detoxifying enzyme characteristic of many progenitor and stem cells, exhibited a relative reduction in survival compared with patients with low levels of ALDH. Given evidence of its role as a CSC marker, we hypothesized that high level of ALDH activity (ALDHhi) in a tumor might positively correlate with the presence of stem- and progenitor-like tumor cells in this disease setting. In support of this hypothesis, ALDH could be used to enrich for CSC in endometrial cancer cell lines and primary tumors, as illustrated by the increased tumor-initiating capacity of ALDHhi cells in immunodeficient mice. ALDHhi cells also exhibited greater clonogenic and organoid-forming capacity compared with ALDHlo cells. Notably, the number of ALDHhi cells in tumor cell lines and primary tumors inversely correlated with differentiation grade. Expression analysis revealed upregulation of IL6 receptor subunits and signal transducers CD126 and GP130 in ALDHhi endometrial cancer cells. Accordingly, targeted inhibition of the IL6 receptor and its downstream effectors JAK1 and STAT3 dramatically reduced tumor cell growth. Overall, our results provide a preclinical rationale to target IL6 or its effector functions as a novel therapeutic option in endometrial cancer. Cancer Res; 75(17); 3608–22. ©2015 AACR.
Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project
Authors: Petrick Jessica L. , Freedman Neal D. , Graubard Barry I. , Sahasrabuddhe Vikrant V. , Lai Gabriel Y. , Alavanja Michael C. , Beane-Freeman Laura E. , Boggs Deborah A. , Buring Julie E. , Chan Andrew T. , Chong Dawn Q. , Fuchs Charles S. , Gapstur Susan M. , Gaziano John Michael , Giovannucci Edward L. , Hollenbeck Albert R. , King Lindsay Y. , Koshiol Jill , Lee I-Min , Linet Martha S. , Palmer Julie R. , Poynter Jenny N. , Purdue Mark P. , Robien Kim , Schairer Catherine , Sesso Howard D. , Sigurdson Alice J. , Zeleniuch-Jacquotte Anne , Wactawski-Wende Jean , Campbell Peter T. , McGlynn Katherine A.
Published: July 2015

Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee–HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer.

Methods: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression.

Results: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53–0.99; Ptrend cups/day = <0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26–0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63–1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50–1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55–1.54). There was no association between coffee consumption and ICC.

Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC.

Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. Cancer Epidemiol Biomarkers Prev; 24(9); 1398–406. ©2015 AACR.
Leisure-Time Spent Sitting and Site-Specific Cancer Incidence in a Large U.S. Cohort
Authors: Patel Alpa V. , Hildebrand Janet S. , Campbell Peter T. , Teras Lauren R. , Craft Lynette L. , McCullough Marjorie L. , Gapstur Susan M.
Published: July 2015

Background: Time spent sitting is distinctly different from accumulating too little physical activity and may have independent deleterious effects. Few studies have examined the association between sitting time and site-specific cancer incidence.

Methods: Among 69,260 men and 77,462 women who were cancer-free and enrolled in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, 18,555 men and 12,236 women were diagnosed with cancer between 1992 and 2009. Extended Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) of leisure-time spent sitting with total and site-specific cancer incidence.

Results: Longer leisure-time spent sitting, after adjustment for physical activity, BMI, and other factors, was associated with risk of total cancer in women (RR = 1.10; 95% CI, 1.04–1.17 for ≥6 hours vs. <3 hours per day), but not men (RR = 1.00; 95% CI, 0.96–1.05). In women, sitting time was associated with risk of multiple myeloma (RR = 1.65; 95% CI, 1.07–2.54), invasive breast cancer (RR = 1.10; 95% CI, 1.00–1.21), and ovarian cancer (RR = 1.43; 95% CI, 1.10–1.87). There were no associations between sitting time and site-specific cancers in men.

Conclusion: Longer leisure-time spent sitting was associated with a higher risk of total cancer risk in women, and specifically with multiple myeloma, breast, and ovarian cancers, but sitting time was not associated with cancer risk in men. Further research is warranted to better understand the differences in associations between men and women.

Impact: For women, these findings support American Cancer Society guidelines for cancer prevention to reduce sitting time when possible. Cancer Epidemiol Biomarkers Prev; 24(9); 1350–9. ©2015 AACR.
CCR 20th Anniversary Commentary: Paving the Way for Circulating Tumor Cells
Authors: Allard W. Jeffrey , Terstappen Leon W.M.M.
Published: July 2015

Cancer cells can enter the bloodstream, form distant metastases, and ultimately lead to death. A study by Allard and colleagues, which was published in the October 15, 2004, issue of Clinical Cancer Research, concluded that the CellSearch system could be used as a reliable tool to investigate circulating tumor cells and their clinical utility, and it spurred a still-growing interest in the field. Clin Cancer Res; 21(13); 2883–5. ©2015 AACR.

See related article by Allard et al., Clin Cancer Res 2004;10(20) October 15, 2004;6897–904
Evaluation of Epigenetic Drug Targeting of Heterogenous Tumor Cell Fractions Using Potential Biomarkers of Response in Ovarian Cancer
Authors: Singh Anand Kamal , Chandra Nishi , Bapat Sharmila A.
Published: July 2015

Purpose: Resolution of aberrant epigenetic changes leading to altered gene expression during transformation and tumor progression is pertinent for mechanistic understanding of disrupted pathways in cancer. Such changes provide for biomarkers that can be applied in drug screening and improved disease management.

Experimental Design: Genome-wide profiling and analyses of promoter DNA methylation, histone modifications, and gene expression of an in vitro progression model of serous ovarian adenocarcinoma were carried out. Similar in silico analyses and comparison of methylation and gene expression of early- and late-grade ovarian cancer samples in The Cancer Genome Atlas assigned a clinical relevance to our study. Candidate biomarkers were evaluated for epigenetic drug treatments in experimental animal models on a background of differing tumor cell responses arising from intratumor heterogeneity.

Results: Differentially regulated genes during tumor progression were identified through the previously mentioned analyses as candidate biomarkers. In examining the tumor suppressor PTGIS as a potential biomarker for treatment with either 5-Aza-dC or TSA, 5-Aza-dC effectively stabilized cell cycling, restricted genetic instability, and derepressed PTGIS expression, while TSA led to emergence of drug-resistant progenitors lacking PTGIS expression. Profiling MEST and RXRγ for curcumin and CBB1007, respectively, indicated an inability of curcumin and CBB1007 in restricting residual tumor regenerative capabilities.

Conclusions: Our study provides novel insights into epigenetic regulation in ovarian cancer progression and potential biomarkers for evaluating efficacy of epigenetic drugs in restricting residual tumor regeneration. Such approaches may assign a new functional interpretation of drug efficacy and cell tumor responses in ovarian cancer. Clin Cancer Res; 21(22); 5151–63. ©2015 AACR.
A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum α-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP
Authors: Morgan Timothy R. , Osann Kathryn , Bottiglieri Teodoro , Pimstone Neville , Hoefs John C. , Hu Ke-Qin , Hassanein Tarek , Boyer Thomas D. , Kong Lorene , Chen Wen-Pin , Richmond Ellen , Gonzalez Rachel , Rodriguez Luz M. , Meyskens Frank L.
Published: July 2015

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential. Cancer Prev Res; 8(9); 864–72. ©2015 AACR.
Are a Double Duct Sign or Endoscopic Biopsies Reliable Predictors of Malignancy in Periampullary Lesions
Authors: ten Berge Josianne C.E.M. , Suker Mustafa , Bruno Marco J. , Poley Jan-Werner , Dwarkasing Roy , Biermann Katharina , van Eijck Casper H.J.
Published: July 2015

Aim: To determine the predictive value of a double duct sign (DDS) and endoscopic biopsies to differentiate invasive carcinoma from premalignant lesions. Methods: Two hundred and forty one patients (mean age 65.8; male 55.6%) diagnosed with a periampullary lesion from January 1987 through March 2013 were reviewed retrospectively with regard to background characteristics, histology of endoscopic biopsy, diameter of both common bile duct (CBD) and main pancreatic duct (PD), bilirubin levels and final diagnosis. Results: DDS predicted malignancy with 73% specificity and 72% sensitivity. Endoscopic biopsies predicted malignancy with 96% specificity, 71% sensitivity and a negative predictive value (NPV) of 51%. Multivariable logistic regression analysis showed that DDS is a significant predictor for the presence of malignancy with an odds ratio of 6.37 adjusted to age, gender and endoscopic biopsy. Conclusion: Although DDS is indicative of malignancy in periampullary lesions, its clinical use is limited, given the low sensitivity and specificity. The diagnostic value of endoscopic biopsies is also poor due to a low sensitivity and NPV. If a double duct sign is present, physicians must be aware of an increased possibility of a malignant underlying cause, even if the histopathological examination of the biopsies did not show invasive malignancy.
Caveolin-1 Confers Resistance of Hepatoma Cells to Anoikis by Activating IGF-1 Pathway
Authors: Tang Wenqing , Feng Xuemei , Zhang Si , Ren Zhenggang , Liu Yinkun , Yang Biwei , lv Bei , Cai Yu , Xia Jinglin , Ge Ningling
Published: July 2015

Background/Aims: Anoikis resistance is a prerequisite for hepatocellular carcinoma (HCC) metastasis. The role of Caveolin-1 (CAV1) in anoikis resistance of HCC remains unclear. Methods: The oncogenic effect of CAV1 on anchor-independent growth and anoikis resistance was investigated by overexpression and knockdown of CAV1 in hepatoma cells. IGF-1 pathway and its downstream signals were detected by immunoblot analysis. Caveolae invagination and IGF-1R internalization was studied by electron microscopy and 125I-IGF1 internalization assay, respectively. The role of IGF-1R and tyrosine-14 residue (Y-14) of CAV1 was explored by deletion experiment and mutation experiment, respectively. The correlation of CAV1 and IGF-1R was further examined by immunochemical analysis in 120 HCC specimens. Results: CAV1 could promote anchor-independent growth and anoikis resistance in hepatoma cells. CAV1-overexpression increased the expression of IGF-1R and subsequently activated PI3K/Akt and RAF/MEK/ERK pathway, while CAV1 knockdown showed the opposite effect. The mechanism study revealed that CAV1 facilitated caveolae invagination and 125I-IGF1 internalization. IGF-1R deletion or Y-14 mutation reversed CAV1 mediated anchor-independent growth and anoikis resistance. In addition, CAV1 expression was positively related to IGF-1R expression in human HCC tissues. Conclusion: CAV1 confers resistance of hepatoma cells to anoikis by activating IGF-1 pathway, providing a potential therapeutic target for HCC metastasis.