bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the efficacy of the electronic patient record system EDeR: implementation study—study protocol
Authors: Job Oliver , Bachmann Lucas M , Schmid Martin K , Thiel Michael A , Ivic Sandra
Published: April 2013

Introduction

Despite many innovations in information technology, many clinics still rely on paper-based medical records. Critics, however, claim that they are hard to read, because of illegible handwriting, and uncomfortable to use. Moreover, a chronological overview is not always easily possible, content can be destroyed or get lost. There is an overall opinion that electronic medical records (EMRs) should solve these problems and improve physicians’ efficiency, patients’ safety and reduce the overall costs in practice. However, to date, the evidence supporting this view is sparse.

Methods and analysis

In this protocol, we describe a study exploring differences in speed and accuracy when searching clinical information using the paper-based patient record or the Elektronische DateneRfassung (EDeR). Designed as a randomised vignette study, we hypothesise that the EDeR increases efficiency, that is, reduces time on reading the patient history and looking for relevant examination results, helps finding mistakes and missing information quicker and more reliably. In exploratory analyses, we aim at exploring factors associated with a higher performance.

Ethics and dissemination

The ethics committee of the Canton Lucerne, Switzerland, approved this study. We presume that the implementation of the EMR software EDeR will have a positive impact on the efficiency of the doctors, which will result in an increase of consultations per day. We believe that the results of our study will provide a valid basis to quantify the added value of an EMR system in an ophthalmological environment.
The new variant ofChlamydia trachomatiswas present as early as 2003 in Örebro County, Sweden, but remained undetected until 2006
Authors: Jurstrand Margaretha , Fredlund Hans , Unemo Magnus
Published: April 2013

Objectives

In 2006, a new variant ofChlamydia trachomatis(nvCT) was reported in Sweden. Because of a cryptic plasmid deletion, the nvCT was undetectable in several of the genetic diagnostic systems used worldwide at the time. This study aimed to evaluate whether the nvCT was present in specimens obtained from patients attending the outpatient sexually transmitted infection (STI) clinic at Örebro University Hospital, Örebro, Sweden already in 2002–2003.

Methods

In 2012, archival (−20°C freezer) urogenital specimens (2002 (n=1083) and in 2003 (n=1143)) obtained from men (2002 (n=398) and 2003 (n=486)) and women (2002 (n=301) and 2003 (n=408)) were analysed with Cobas TaqMan CT test V.2.0. AllC trachomatispositive specimens were subsequently examined using a duplex PCR assay that simultaneously detects the deletion on the nvCT cryptic plasmid and theompAgene ofC trachomatisgenotype E.

Results

In total, 68 patients (9.7%) in 2002 and 61 (6.8%) in 2003 wereC trachomatispositive. The duplex PCR assay identified 26C trachomatisgenotype E positive patients in 2002 (38%) and 25 in 2003 (41%). No nvCT was found in 2002, but one specimen obtained from a 23-year-old man in June 2003 was positive for the nvCT.

Conclusions

The nvCT was present as early as 2003 in Örebro County, Sweden, which concurs with previously reported statistical estimations of its emergence. Accordingly, the nvCT spread undetected for at least 3 years, explaining the high proportion (38%) in Örebro County when it was first detected in late 2006.
ON THE FACTORIZATION OF THE SCATTERING OF W BOSONS
Authors: FRANCESCHINI ROBERTO
Published: April 2013

Recent results on the application of the method of the effective quanta to the case of WW scattering are reviewed. In particular, it is reviewed how effective W bosons can be used to compute scattering amplitudes in a generalized Effective W Approximation (gEWA). The physical origin and the expected size of the discrepancy between the exact computation and the gEWA computation are discussed. Particular attention is devoted to the peculiarities of the formulation of the gEWA for processes that involve longitudinal W bosons. These formal results are checked through explicit numerical calculations of both scattering amplitudes and scattering cross-sections. Furthermore, the use of the gEWA for the interpretation and for the presentation of the measurement of WW scattering at the LHC is briefly discussed.
A REMARK ON ROBERTS' TOTALLY TWISTED KHOVANOV HOMOLOGY
Authors: JAEGER THOMAS C.
Published: April 2013

We offer an alternative construction of Roberts' totally twisted Khovanov homology and prove that for knots, it agrees with δ-graded reduced characteristic-2 Khovanov homology.
RENORMALIZATION OF COHERENT STATE VARIABLES, WITHIN THE GEOMETRICAL MAPPING OF ALGEBRAIC MODELS
Authors: YÉPEZ-MARTÍNEZ H. , MORALES-HERNÁNDEZ G. E. , HESS P. O. , LÉVAI G. , FRASER P. R.
Published: April 2013

We investigate the geometrical mapping of algebraic models. As particular examples we consider the semimicriscopic algebraic cluster model (SACM) and the phenomenological algebraic cluster model (PACM), which also contains the vibron model as a special case. In the geometrical mapping, coherent states are employed as trial states. We show that the coherent state variables have to be renormalized and not the interaction terms of the Hamiltonian, as is usually done. The coherent state variables will depend on the total number of bosons and the coherent state variables. The nature of these variables is extracted through a relation obtained by comparing physical observables, such as the distance between the clusters or the quadrupole deformation of the nucleus, to their algebraic counterpart.
INTUITIONISTIC FUZZY DECISION-MAKING WITH SIMILARITY MEASURES AND OWA OPERATOR
Authors: SU WEIHUA , YANG YONG , ZHANG CHONGHUI , ZENG SHOUZHEN
Published: April 2013

In this paper, we present a new intuitionistic fuzzy decision-making technique based on similarity measures and the ordered weighted average (OWA) operator. We develop the intuitionistic fuzzy ordered weighted similarity (IFOWS) measure. The main advantage of the IFOWS measure is that it can alleviate the influence of unduly large (or small) deviations on the aggregation results by assigning them low (or high) weights. Moreover, it provides a very general formulation that includes a wide range of aggregation similarity measures and aggregates the input arguments taking the form of intuitionistic fuzzy values rather than exact numbers. We further develop the interval-valued intuitionistic fuzzy ordered weighted similarity (IVIFOWS) measure. Then we apply the developed similarity measures for consensus analysis in group decision-making with intuitionistic fuzzy information. Finally, a practical case is used to illustrate the developed procedures.
The Other Month Effect: A Re-Examination of the "Other January" Anomaly
Authors: Darrat Ali F. , Li Bin , Chung Richard
Published: April 2013

Cooper et al. (2006) find support for the "other January" effect in the US market over the period from January 1940 to December 2003 whereby the 11-month holding period returns following positive January returns are on average higher than those 11 months following negative January returns. Under this scenario, January returns can predict the subsequent 11-month holding period returns implying the potential for abnormal profits. We revisit this "anomaly" in the US stock market using the extended period from July 1926 to January 2012. Over the shorter period of 1940–2003 used by CMO, the results are supportive of the "other January" effect and they do so for several alternative holding periods. However, this alleged "other January" effect disappears once we expand the period. Moreover, we find similar and perhaps stronger anomalies for non-January months, particularly February and September. The evidence we uncover in this paper suggests that this alleged "other January" effect is likely sample-period sensitive and further, it is not specific to the month of January.
EFFECT OF LIQUID VISCOSITY ON INSTABILITY OF HIGH-SPINNING PARTIALLY-FILLED SHELL ROTORS
Authors: FIROUZ-ABADI R. D. , PERMOON M. R.
Published: April 2013

In this study, the instability of spinning cylindrical shells partially filled with viscous liquid is investigated. Based on the Navier–Stokes equations for the incompressible flow, a 2D model is developed for liquid motion at each section of the cylinder. The governing equations of the cylinder vibrations are obtained based on the first-order shear deformable shell theory. The nonpenetration and no-slip boundary conditions of the flow on the wetted surface of the cylinder relate the liquid motion to the shell vibrations. Also the liquid pressure exerted on the cylinder wall combines the vibrations of the rotary cylinder to the liquid motion. By using the obtained coupled liquid-structure model, the instability conditions of the system are determined. The governing parameters of the rotor vibrations are introduced and their influence on the stability boundaries of the rotor is studied.
BISTABLE CHARACTERISTICS OF IRREGULAR ANTI-SYMMETRIC LAY-UP COMPOSITE CYLINDRICAL SHELLS
Authors: ZHANG ZHENG , WU HELONG , WU HUAPING , HE XIAOQIAO , BAO YUMEI , CHAI GUOZHONG
Published: April 2013

The bistable characteristics of the irregular anti-symmetric cylindrical shell (IACS), such as [+α1/ -α2/ +α2/ -α1] lay-up, are presented using theoretical methodology and finite element (FE) analysis. A novel approach named two points loading method is used to induce a snap-through of the shell in FE analysis. Unlike regular [+α/ -α/ +α/ -α] lay-up anti-symmetric cylindrical shells, two or more different ply angles are included in the irregular anti-symmetric lay-up. Besides ply angles, the bistable characteristics of composite cylindrical shells with irregular anti-symmetric lay-ups are also affected by the sequence of lay-ups. Both analytical and FE results show that IACS with different bistable behaviors can be obtained by changing the ply angles or sequence of the lay-ups. It is very useful for the design and manufacture of the bistable structure. There is a reasonable agreement between analytical and FE predictions; possible reasons of differences between analytical and FE results are given.
Salt pillows and localization of early structures: case study in the Ucayali Basin (Peru)
Authors: Moretti I. , Callot J. P. , Principaud M. , Pillot D.
Published: April 2013

In many compressive zones, there is a risk of undercharged hydrocarbon prospects as a result of timing, that is, the growth of the structure is younger than the main fluid migration phase. The North Ucayali Basin represents a setting of this type, where locating the earliest structures is crucial for well placement. In the North Ucayali Basin, the variable amount of erosion at the top of the structures shows that they are not uniformly recent. Although the growth of early structures may be explained by the reactivation of inherited features during shortening, evaporitic pillows may represent an alternative factor controlling the localization of deformation in the studied area. Indeed, subsurface data reveal the presence of flat salt domes that have an influence on thrust localization. The existence and tips of such efficient gliding surfaces concentrate the strain and, as a result, localize the early zones of deformation. Analogue models designed to study these phenomena highlight the crucial role of salt pillows as potential weak zones localizing deformation ahead of the propagating wedge. These models also emphasize the need to constrain certain parameters that have been previously disregarded, including the thickness of the brittle layers between the main décollement level (if present) and the pillows, as well as their burial depth.
Bismuth-Carbon Nanotube Composite Modified Carbon Paste Electrode for the Determination of Heavy Metal Ions
Authors: Pikroh Nantana , Vanalabhpatana Parichatr
Published: April 2013

A new, easy-to-handle, and inexpensive bismuth-carbon nanotube composite modified carbon paste electrode or Bi-CNT/CPE was developed for the simultaneous determination of cadmium(II) and lead(II) ions in an acetate buffer solution (pH 4.5) by square wave anodic stripping voltammetry. Synthesized through polyol process, Bi-CNT composite served as a source of ready-to-use bismuth and also held unique chemical and physical properties of CNTs. Compared to the previously fabricated Bi-CNT modified glassy carbon electrode (Bi-CNT/GCE), Bi-CNT/CPE exhibited superior electrochemical performance, leading to further optimization of this novel Bi-CNT/CPE for metal-ion detection.
Development and Study of Tantalum and Niobium Carbides as Electrocatalyst Supports for the Oxygen Electrode for PEM Water Electrolysis at Elevated Temperatures
Authors: Nikiforov Aleksey Valerievich , Petrushina Irina M. , Prag Carsten B. , Polonský Jakub , Christensen Erik , Bjerrum Niels J.
Published: April 2013

Polymer electrolyte membrane (PEM) water electrolysis is a prospective method of producing hydrogen. We focused on one of its issues - the lack of a suitable support material for the anode electrocatalyst. TaC and NbC were studied as possible electrocatalyst supports for the PEM water electrolysis. Resistance to oxidation of the TaC and NbC was investigated by exposing them to air at 84 and 150 ºC. Subsequently, their electrical conductivity was measured as the indicator of oxidation. Change in specific surface area and conductivity was measured after different periods of ball milling. We found that the TaC was significantly more resistant to oxidation than the NbC. Eventually, both materials retained relatively high electrical conductivity even with the oxidized surface. TaC can thus be recommended as an electrocatalyst support for the oxygen evolution reaction and both materials are proposed to be tested as alternative electrocatalyst supports for the hydrogen evolution reaction.
Efficient Oxygen Evolution on Spray Pyrolytically Synthesized Ni, Co and Mixed Ni-Co Oxides on FTO Coated Glass Substrate during Water Electrolysis
Authors: Frites Mourad , Khan Shahed U.M.
Published: April 2013

The Ni-oxide, Co-oxide and the mixed Ni-Co oxide anodes were synthesized from their respective salt solutions using the spray pyrolysis method for efficient oxygen evolution reaction (OER) during water electrolysis. The mixed Ni-Co-oxides were found more electrocatalytic compared to their respective oxides and showed lowest Tafel slope of 160 mV/decade compared to 305 mV/decade and 233 mV/decade for Ni-oxide and Co-oxide respectively. At measured applied potential of 1.00 V/SCE the mixed Ni-Co oxide anode generated a current density of 145.0 mA cm-2 compared to 30.0 mA cm-2 for OER at their individual oxide surfaces. These current densities corresponded to O2 evolution rates of 1.35 mMol cm-2 h-1 at Ni-Co oxide anode and 0.28 mMol O2 cm-2 h-1 at both Ni-oxide and Co-oxide anodes. These results indicate over four-fold increase in OER rate at the mixed Ni-Co oxide anode due to synergetic effect of both oxides compared to their individual oxide surfaces.
Fuel Cell Performance Using a Phosphonated Polysulphone Ionomer (PSUgPVPA) in the PEM Cathode Electrode
Authors: Wreland Lindström Rakel , Guerrero Aguinaga Luis , Oyarce Alejandro , Ubeda Diego , Ingratta Mark , Jannasch Patric , Lindbergh Göran
Published: April 2013

Inexpensive and environmentally friendly electrolyte polymers that can be operated at higher temperatures and drier conditions are highly interesting for PEM fuel cells for automotive, portable power and stationary electricity generation applications. In this study an ionomer based on polysulfone grafted with poly(vinylphosphonic acid) (PSUgPVPA) in the cathode Pt/C catalyst layer (CL) was electrochemically characterized and compared to Nafion. The performance at different levels of humidity at 80 ºC was evaluated by polarization and cyclic voltammetry. The results show that the performance of the PSUgPVPA-based cathode CL is comparable to that of Nafion at 100% relative humidity (RH) but with some instabilities. However, at drier conditions significant losses of performance for the PSUgPVPA-based cathode was observed, concomitant to a reduced electrochemical surface area. The lower performance at low humidity is concluded to be due to a combination of lower proton conductivity and wettability or interference with oxygen reduction reaction at lower RH.
Electrodeposition of Ni-Zn Alloys on Steel from Acidic Solution in Presence of Boric Acid
Authors: Addi Yassine , Khouider Ali
Published: April 2013

The electrode position of nickel with zinc in presence of boric acid was studied in order to determine the influence of the composition of the deposition solution on the properties of the obtained electrodeposits. The Ni / Zn concentrations ratio in solution determines the deposition mechanism and thus, the chemical composition and the electrochemical activity of the electrodeposited alloys. Boric acid decreases current density which minimizes anomalous deposition. The typical results from these acidic media are the formation of Ni-rich alloys (%Ni > 90) by a normal code position mechanism with a better electrochemical activity than Ni for the hydrogen evolution reaction HER reaction. Results show that it is possible to obtain alloys rich in either zinc or nickel, from an acidic solution containing boric acid. For Ni / Zn concentration ratios in the range of 1-3, Zn-rich alloys are obtained despite Zn is the less noble element and even when it is present at lower concentrations than Ni, confirming that at these conditions alloys are deposited by an anomalous deposition mechanism as reported by many researchers1,2,3
A Multiscale Physical Model of Electrochemical Energy Storage Devices
Authors: Franco Alejandro A.
Published: April 2013

A general multiscale physical modeling framework is presented to simulate the transient operation and mechanisms at multiple scales in electrochemical storage systems, such as lithium air batteries, lithium ion batteries and supercapacitors. This approach extends the one developed by my group and myself since 10 years for PEM Fuel Cells and Water Electrolyzers. The framework consists on detailed modular descriptions of the elementary kinetic reactions within the electrodes that can be based on ab initio-extracted parameters and the description of the electrochemical double layer formation under nonequilibrium conditions, micro and mesoscale structurally-resolved description of charges transfer across the porous media and cell potential calculation. This general approach allows accounting for the explicit transient description of materials degradation mechanisms and their impact on the instantaneous cell performance decay rate and durability. The specific application of this model to the case of lithium-air batteries is illustrated.
Electrochemical Sensing of Trypsin Activity
Authors: Arredondo Michelle , Stoytcheva Margarita , Zlatev Roumen , Cosnier Serge
Published: April 2013

In this work is reported a rapid and sensitive electrochemical method for trypsin activity determination, based on the use of a gelatin coated glassy carbon electrode and registration of the current of hydroquinone oxidation depending on trypsin activity. The hydrogel film creates a kinetic barrier for the transport of the electroactive species to the electrode surface. The progressive trypsin catalyzed film digestion causes increase of its permeability, resulting in increase of the hydroquinone oxidation current. Current increase dependence on trypsin activity was investigated under various experimental conditions: hydrogel film thickness, hydroquinone solution concentration, and incubation time. Current response as a function of trypsin concentration within 10 min of incubation time was evaluated in the range of 0.1 to1000 μg mL-1. The limit of detection achieved in optimal conditions was found to be 0.01 μg L-1. The proposed approach allows trypsin sensing in the normal and acute pancreatitis range.
Digestive and respiratory tract motor responses associated with eructation
Authors: Lang Ivan M. , Medda Bidyut K. , Shaker Reza
Published: April 2013

We studied the digestive and respiratory tract motor responses in 10 chronically instrumented dogs during eructation activated after feeding. Muscles were recorded from the cervical area, thorax, and abdomen. The striated muscles were recorded using EMG and the smooth muscles using strain gauges. We found eructation in three distinct functional phases that were composed of different sets of motor responses: gas escape, barrier elimination, and gas transport. The gas escape phase, activated by gastric distension, consists of relaxation of the lower esophageal sphincter and diaphragmatic hiatus and contraction of the longitudinal muscle of the thoracic esophagus and rectus abdominis. All these motor events promote gas escape from the stomach. The barrier elimination phase, probably activated by rapid gas distension of the thoracic esophagus, consists of relaxation of the pharyngeal constrictors and excitation of dorsal and ventral upper esophageal sphincter distracting muscles, as well as rapid contraction of the diaphragmatic dome fibers. These motor events allow esophagopharyngeal air movement by promoting retrograde airflow and opening of the upper esophageal sphincter. The transport phase, possibly activated secondary to diaphragmatic contraction, consists of a retrograde contraction of the striated muscle esophagus that transports the air from the thoracic esophagus to the pharynx. We hypothesize that the esophageal reverse peristalsis is mediated by elementary reflexes, rather than a coordinated peristaltic response like secondary peristalsis. The phases of eructation can be activated independently of one another or in a different manner to participate in physiological events other than eructation that cause gastroesophageal or esophagogastric reflux.
The sGC activator BAY 60-2770 has potent erectile activity in the rat
Authors: Lasker George F. , Pankey Edward A. , Frink Terrence J. , Zeitzer Jonathan R. , Walter Korey A. , Kadowitz Philip J.
Published: April 2013

Nitric oxide (NO) is the principal mediator of penile erection, and soluble guanylate cyclase (sGC) is the receptor for NO. In pathophysiological conditions when sGC is inactivated and not responsive to NO or sGC stimulators a new class of agents called sGC activators increase the activity of NO-insensitive sGC and produce erection. The aim of this study was to investigate erectile responses to BAY 60-2770, a sGC activator, under physiological and pathophysiological conditions. In the present study increases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 60-2770 were investigated under baseline conditions, when sGC was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), when nitric oxide synthase (NOS) was inhibited by N-nitro-l-arginine methyl ester (l-NAME), and after cavernosal nerve crush injury. Under baseline conditions ic injections of BAY 60-2770 increase ICP, ICP/mean arterial pressure (MAP), and area under the ICP curve (AUC) and produce small decreases in MAP at the highest doses studied. BAY 60-2770 was very potent in its ability to induce erection and responses to BAY 60-2770 were enhanced by ODQ which attenuates erectile responses to sodium nitroprusside (SNP), diethylamine NONOate (DEA/NO), and cavernosal nerve stimulation. Responses to BAY 60-2770 were not altered by l-NAME or cavernosal nerve crush injury. These data indicate that BAY 60-2770 has potent erectile activity that is enhanced by ODQ and show that responses to BAY 60-2770 are not attenuated by NOS inhibition or cavernosal nerve injury. These results suggest that BAY 60-2770 would be effective in the treatment of erectile dysfunction when NO bioavailability is reduced, after pelvic nerve injury, and when sGC is oxidized.
Respiratory influences on muscle sympathetic nerve activity and vascular conductance in the steady state
Authors: Limberg Jacqueline K. , Morgan Barbara J. , Schrage William G. , Dempsey Jerome A.
Published: April 2013

In patients with hypertension, volitional slowing of the respiratory rate has been purported to reduce arterial pressure via withdrawal of sympathetic tone. We examined the effects of paced breathing at 7, 14, and 21 breaths/min, with reciprocal changes in tidal volume, on muscle sympathetic nerve activity, forearm blood flow, forearm vascular conductance, and blood pressure in 21 men and women, 8 of whom had modest elevations in systemic arterial pressure. These alterations in breathing frequency and volume did not affect steady-state levels of sympathetic activity, blood flow, vascular conductance, or blood pressure (all P > 0.05), even though they had the expected effect on sympathetic activity within breaths (i.e., increased modulation during low-frequency/high-tidal volume breathing) ( P < 0.001). These findings were consistent across subjects with widely varied baseline levels of sympathetic activity (4-fold), mean arterial pressure (78–110 mmHg), and vascular conductance (15-fold), and those who became hypocapnic during paced breathing vs. those who maintained normocapnia. These findings challenge the notion that slow, deep breathing lowers arterial pressure by suppressing steady-state sympathetic outflow.
Single Copies of Mutant KRAS and Mutant PIK3CA Cooperate in Immortalized Human Epithelial Cells to Induce Tumor Formation
Authors: Wang Grace M. , Wong Hong Yuen , Konishi Hiroyuki , Blair Brian G. , Abukhdeir Abde M. , Gustin John P. , Rosen D. Marc , Denmeade Samuel Ray , Rasheed Zeshaan , Matsui William , Garay Joseph P. , Mohseni Morassa , Higgins Michaela J. , Cidado Justin , Jelovac Danijela , Croessmann Sarah , Cochran Rory L. , Karnan Sivasundaram , Konishi Yuko , Ota Akinobu , Hosokawa Yoshitaka , Argani Pedram , Lauring Josh , Park Ben Ho
Published: April 2013

The selective pressures leading to cancers with mutations in both KRAS and PIK3CA are unclear. Here, we show that somatic cell knockin of both KRAS G12V and oncogenic PIK3CA mutations in human breast epithelial cells results in cooperative activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in vitro, and leads to tumor formation in immunocompromised mice. Xenografts from double-knockin cells retain single copies of mutant KRAS and PIK3CA, suggesting that tumor formation does not require increased copy number of either oncogene, and these results were also observed in human colorectal cancer specimens. Mechanistically, the cooperativity between mutant KRAS and PIK3CA is mediated in part by Ras/p110α binding, as inactivating point mutations within the Ras-binding domain of PIK3CA significantly abates pathway signaling. In addition, Pdk1 activation of the downstream effector p90RSK is also increased by the combined presence of mutant KRAS and PIK3CA. These results provide new insights into mutant KRAS function and its role in carcinogenesis. Cancer Res; 73(11); 3248–61. ©2013 AACR.
MTA1 Promotes STAT3 Transcription and Pulmonary Metastasis in Breast Cancer
Authors: Pakala Suresh B. , Rayala Suresh K. , Wang Rui-An , Ohshiro Kazufumi , Mudvari Prakriti , Reddy Sirigiri Divijendra Natha , Zheng Yi , Pires Ricardo , Casimiro Sandra , Pillai M. Radhakrishna , Costa Luis , Kumar Rakesh
Published: April 2013

Overexpression of the prometastatic chromatin modifier protein metastasis tumor antigen 1 (MTA1) in human cancer contributes to tumor aggressiveness, but the role of endogenous MTA1 in cancer has not been explored. Here, we report the effects of selective genetic depletion of MTA1 in a physiologically relevant spontaneous mouse model of breast cancer pulmonary metastasis. We found that MTA1 acts as a mandatory modifier of breast-to-lung metastasis without effects on primary tumor formation. The underlying mechanism involved MTA1-dependent stimulation of STAT3 transcription through action on the MTA1/STAT3/Pol II coactivator complex, and, in turn, on the expression and functions of STAT3 target genes including Twist1. Accordingly, we documented a positive correlation between levels of MTA1 and STAT3 in publicly available breast cancer data sets. Together, our findings reveal an essential modifying role of the physiologic level of MTA1 in supporting pulmonary metastasis of breast cancer. Cancer Res; 73(12); 3761–70. ©2013 AACR.
Diabetes Mellitus and Prostate Cancer Risk; A Nationwide Case–Control Study within PCBaSe Sweden
Authors: Fall Katja , Garmo Hans , Gudbjörnsdottir Soffia , Stattin Pär , Zethelius Björn
Published: April 2013

Background: Diabetes mellitus (DM) increases the risk for cancer at almost all sites, but data on the association with prostate cancer are inconsistent.

Methods: We assessed the risk of a prostate cancer diagnosis among men with type 2 (T2)DM in a nationwide population-based case-control study including 44,352 men with prostate cancer identified through the Prostate Cancer data Base Sweden (PCBaSe) between 2002 and 2006 and 221,495 age-matched men from the general population.

Results: Overall, the risk of prostate cancer among men with T2DM was lower than among men without T2DM [OR, 0.80; 95% confidence interval (CI), 0.76–0.85]. The risk decreased with longer disease duration and was observed across all tumor risk categories, although most clearly among men with low risk tumors (OR, 0.71; 95% CI, 0.64–0.80). The risk for prostate cancer was reduced among diabetic men on dietary treatment only (OR, 0.89; 95% CI, 0.80–0.99) but more markedly among men on oral hypoglycemic agents (OR, 0.80; 95% CI, 0.74–0.87) and insulin (OR, 0.72; 95% CI, 0.69–0.81). Obese diabetic men (BMI > 30 kg/m2) showed a reduced risk (OR, 0.72; 95% CI, 0.65–0.80) compared with men without diabetes. There was a trend of decreasing risk with increasing levels of HbA1c (P < 0.05).

Conclusions: This nationwide study confirmed a reduced risk of being diagnosed with prostate cancer among men with T2DM, especially for low-risk tumors. An altered hormonal milieu is a plausible explanation, although the possibility of decreased prostate cancer detection among diabetic men cannot be ruled out.

Impact: This is the largest study to examine the association between T2DM and prostate cancer accounting for tumor risk group and diabetes treatment. Cancer Epidemiol Biomarkers Prev; 22(6); 1102–9. ©2013 AACR.
Smokeless and Dual Tobacco Use Among Males Surviving Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Klosky James L. , Hum Ashley M. , Zhang Nan , Ali Khatidja S. , Srivastava D. Kumar , Klesges Robert C. , Emmons Karen M. , Ness Kirsten K. , Stovall Marilyn , Robison Leslie L. , Hudson Melissa M.
Published: April 2013

Cancer survivors experience treatment-related complications that can be exacerbated by tobacco use. This study reports the prevalence of smokeless and dual tobacco use, compares these rates to the U.S. population, and examines tobacco risk factors among males surviving childhood cancer. Data from the Childhood Cancer Survivor Study (CCSS) 2007 survey were used (N = 3378). Standardized incidence ratios (SIR) were obtained by comparing CCSS data with the National Survey on Drug Use and Health. Logistic regression was used to evaluate associations between risk factors and tobacco use. Among male survivors, 8.3% and 2.3% were current smokeless tobacco and dual tobacco users, respectively. Survivors were less likely than population males to report smokeless tobacco [SIR = 0.64; 95% confidence interval (CI), 0.57–0.72) or dual tobacco (SIR = 0.37; CI, 0.29–0.46) use; however, non-White survivors aged 35 to 49 years were more likely to use smokeless tobacco (SIR = 2.32; CI, 1.27–3.90). Smokeless tobacco use was associated (P < 0.05) with younger age at diagnosis, lower education, being married or divorced/separated, and not living in the Northeastern United State, whereas history of cardiovascular- and/or pulmonary-toxic treatment was protective. Dual tobacco use was associated with younger age at diagnosis, lower education, divorce/separation, and high psychologic distress. Having active heart or circulatory conditions was protective. Although smokeless tobacco/dual tobacco use is generally low among childhood cancer survivors, these findings suggest that tobacco use screening should be expanded to include smokeless tobacco use, and that smokeless tobacco-specific education and cessation interventions should be provided to users. Screening and intervening for smokeless tobacco/dual tobacco use in childhood cancer survivors will reduce tobacco-related morbidity and mortality. Cancer Epidemiol Biomarkers Prev; 22(6); 1025–9. ©2013 AACR.
A Proposal Regarding Reporting of In Vitro Testing Results
Authors: Smith Malcolm A. , Houghton Peter
Published: April 2013

The high rate of negative clinical trials and failed drug development programs calls into question the use of preclinical testing as currently practiced. An important issue for the in vitro testing of agents that have advanced into the clinic is the use of clinically irrelevant concentrations in reports making claims for anticancer activity, as illustrated by publications for sorafenib, vorinostat, and metformin. For sorafenib, high protein binding leads to a dichotomy between concentrations active in the 10% serum conditions commonly used for in vitro testing and concentrations active in plasma. Failure to recognize this distinction leads to inappropriate claims of activity for sorafenib based on the micromolar concentrations commonly used for in vitro testing in low serum conditions. For vorinostat and metformin, results using in vitro concentrations higher than those achievable in patients are reported despite the availability of publications describing human pharmacokinetic data for each agent. We encourage journal editors and reviewers to pay greater attention to clinically relevant concentrations when considering reports that include in vitro testing of agents for which human pharmacokinetic data are available. Steps taken to more carefully scrutinize activity claims based on in vitro results can help direct researchers away from clinically irrelevant lines of research and toward lines of research that are more likely to lead to positive clinical trials and to improved treatments for patients with cancer. Clin Cancer Res; 19(11); 2828–33. ©2013 AACR.
Percutaneous Nephrolithotomy in High-Risk Patients: A Single-Center Experience with More than 350 Cases
Authors: Nouralizadeh Akbar , Lashay Alireza , Ziaee Seyed Amir Mohsen , Ahanian Ali , Sharifi Seyed Hossein Hosseini , Nikkar Mohammad Masoud , Ojand Ardalan , Soltani Mohammad Hossein
Published: April 2013

Purpose: To assess the surgical outcomes and peri- and postoperative complications following percutaneous nephrolithotomy (PCNL) in high- and low-risk patients according to the American Society of Anesthesiologists (ASA) score. Materials and Methods: We reviewed the patient records of 2,281 cases older than 18 years who had undergone PCNL in the 3 previous years. The patients were divided into two groups: a low-risk group (ASA score 1, 2: 1,922 cases) and a high-risk group (ASA score 3, 4: 359 cases). Results: Analysis of the location and size of the stone, number and type of access, surgical approach, post-PCNL serum hemoglobin and decrease in glomerular filtration rate revealed no significant difference between the two groups. The stone-free rate was similar in both groups and the hospital stay in the high-risk patients was significantly greater than in the low-risk cases. 95% of low-risk and 91% of high-risk cases had surgical complications compatible with grade ≤II (Clavien system) and overall distribution of different grades of surgical complications was similar between the two groups (p = 0.177). Conclusion: Success rate and surgical complications of PCNL in high-risk patients were comparable to low-risk patients. It seems that PCNL may be a safe and effective procedure even in high-risk patients.
Novel PCR Assay for Determining the Genetic Sex of Mice
Authors: McFarlane L. , Truong V. , Palmer J.S. , Wilhelm D.
Published: April 2013

A number of studies require the determination of the genetic sex of mouse embryos before sexual differentiation and/or of mutant mice that display partial or complete sex reversal. The majority of current methods for sexing by PCR involve multiplexing of 2 primer pairs. We have developed a novel sexing PCR using a single primer pair that amplifies fragments from the X and the Y chromosome with a clear size difference between the respective amplicons. This assay provides a rapid and reliable method to identify the genetic sex of mice across different mouse strains.
The Role of Ovarian Surface Epithelium in Folliculogenesis during Fetal Development of the Bovine Ovary: A Histological and Immunohistochemical Study
Authors: Kenngott R.A.-M. , Vermehren M. , Ebach K. , Sinowatz F.
Published: April 2013

Although many aspects of ovarian differentiation have been established, comparatively little is known about prenatal follicle formation and differentiation of bovine ovaries. The objective of this investigation was to study the role of the surface epithelium during the development of germ cell nests, germ cell cords and follicle formation in the fetal bovine ovary. Associated important proliferation and apoptotic features were further investigated. Additionally, the expression pattern of the S100 protein was detected. A strong increase of mitotic figures was detected in the surface epithelium, germ cell nests and germ cell cords of ovaries with a crown-rump length (CRL) of 13.0-58.0 cm. Oocytes were positively stained with S100 in bovine ovaries from fetuses with a CRL of 21.0 cm. The staining intensity enhanced parallel to increasing oocyte and follicle sizes during the ovary development. In later stages, a strong staining for S100 was observed in healthy oocytes in contradistinction to atretic oocytes where no expression of the S100 protein could be found. In conclusion, increasing mitosis index of surface epithelium cells, as well as oogonia directly beneath the surface epithelium, in combination with open surface connection during stages from a CRL of 11.0-94.0 cm of bovine fetal ovaries could play an important role in the period of time of ongoing folliculogenesis and derivation of granulosa cells. Additionally, S100-positive oocytes in primordial and later follicle stages joined by a high rate of Ki67-positive index in surrounding granulosa cells indicate that in the oocytes the S100 protein can perhaps be a useful marker for intact oocytes in bovine ovaries.
Potential Bias in the Bank: What Distinguishes Refusers, Nonresponders and Participants in a Clinic-Based Biobank?
Authors: Ridgeway J.L. , Han L.C. , Olson J.E. , Lackore K.A. , Koenig B.A. , Beebe T.J. , Ziegenfuss J.Y.
Published: April 2013

Background: Biobanks are an important resource for genetic and epidemiologic research, but bias may be introduced if those who accept the recruitment invitation differ systematically from those who do not in terms of attributes important to health-related investigations. To understand potential bias in a clinic-based biobank of biological samples, including genetic data linked to electronic health record information, we compared patient characteristics and self-reported information among participants, nonresponders and refusers. We also compared reasons for nonparticipation between refusers and nonresponders to elucidate potential pathways to reduce nonparticipation and any uncovered bias. Methods: We mailed recruitment packets to 1,600 adult patients with upcoming appointments at Mayo Clinic (Rochester, Minn., USA) and recorded their participation status. Administrative data were used to compare characteristics across groups. We used phone interviews with 26 nonresponders and 26 refusers to collect self-reported information, including reasons for nonparticipation. Participants were asked to complete a mailed questionnaire. Results: We achieved 26.2% participation (n = 419) with 12.1% refusing (n = 193) and 61.8% nonresponse (n = 988). In multivariate analyses, sex, age, region of residence, and race/ethnicity were significantly associated with participation. The groups differed in information-seeking behaviors and research experience. Refusers more often cited privacy concerns, while nonresponders more often identified time constraints as the reason for nonparticipation. Conclusion: For genomic medicine to advance, large, representative biobanks are required. Significant associations between patient characteristics and nonresponse, as well as systematic differences between refusers and nonresponders, could introduce bias. Oversampling or recruitment changes, including heightened attention to privacy protection and participation burden, may be necessary to increase participation among less-represented groups.
Are Triplicate Urine Samples Necessary to Assess Albuminuria?
Authors: Deeb Abbas , Zaoui Philippe , Le Penven Salima , Tartry David , Lantelme Pierre , Ducher Michel , Fauvel Jean-Pierre
Published: April 2013

Background/Aims: Urinary albumin excretion is subject to intra-individual variability. Thus, for research purposes, it is recommended to test three urine samples collected over a short period of time. The objective of our analysis was to check the usefulness of triplicate samples to determine the albuminuric status of diabetic patients. Methods: We present the results of the non-planned retrospective analysis of 246 triplicate morning urine samples obtained from 95 type 2 diabetics included in three multinational, randomized, double-blind studies. Albuminuria was determined by immunoturbidimetry on fresh samples in the same central laboratory. Microalbuminuria was defined by a urine albumin to creatinine ratio (UACR) between 2.5 and 25 mg/mmol in males and between 3.5 and 35 mg/mmol in females. Concordance was obtained when the second and/or third sample (UACR2 and UACR3) confirmed the albuminuric status obtained from the first sample (UACR1). Results: Considering the first samples, 9% were within the normal range, 35% showed microalbuminuria and 56% showed macroalbuminuria. The overall concordance rate was 95%. The log of UACR was highly correlated between samples. Bland-Altman plots expressed in percent variations between two samples confirmed that the mean variation was low (around 8%) but revealed the scattering of values, 95% being between -60 and +77% of variation between samples. Conclusions: There is no benefit in repeating morning UACR determination in diabetic patients to accurately categorize a subject as having normo-, micro- or macroalbuminuria. However, in order to accurately quantify albuminuria, repeated determinations are required.
Varicella Zoster Virus Myelitis in Two Elderly Patients: Diagnostic Value of Nested Polymerase Chain Reaction Assay and Antibody Index for Cerebrospinal Fluid Specimens
Authors: Takahashi Teruyuki , Tamura Masato , Miki Kenji , Yamaguchi Mai , Kanno Akira , Nunomura Satoshi , Ra Chisei , Tamiya Takashi , Kamei Satoshi , Takasu Toshiaki
Published: April 2013

Background: Myelitis is one of the rarest neurological complications of the varicella zoster virus (VZV) infection. Focal muscle weakness with or without sensory disturbance occurs in approximately 5% of the cases after acute VZV infection, with complete recovery in 50-70%. Case Presentation: This report describes two rare cases of elderly patients with VZV myelitis secondary to dermatomal zoster rash. Patient 1 was a 79-year-old woman who developed paraplegia, numbness and decreased sensation in the left arm and below thoracic (Th)-10 after sacral zoster. Spinal cord MRI showed a high-signal-intensity lesion at the cervical spinal nerve 2 on a T2-weighted image. Patient 2 was a 73-year-old man who developed right flaccid leg weakness and urinary retention after right dorsal Th 5-8 zoster. Spinal cord MRI showed a high-signal-intensity lesion at Th 3-4 on a T2-weighted image. In both cases, although the conventional single polymerase chain reaction (PCR) assays all showed negative results, the original nested PCR assay detected VZV DNA in the cerebrospinal fluid (CSF) specimen collected on admission. In addition, the anti-VZV IgG antibody by enzyme immunoassay and antibody index were elevated in the CSF specimens during the clinical courses of both patients. On the basis of these findings, both patients were diagnosed with VZV myelitis and were treated with high-dose acyclovir and corticosteroid. This combined treatment was appropriate and effective for the improvement of their functional outcomes. Conclusion: The detection of VZV DNA in CSF by nested PCR assay and the evaluation of the antibody index to VZV had significant diagnostic value.
Liver X Receptor Regulates Arachidonic Acid Distribution and Eicosanoid Release in Human Macrophages
Authors: Ishibashi Minako , Varin Alexis , Filomenko Rodolphe , Lopez Tatiana , Athias Anne , Gambert Philippe , Blache Denis , Thomas Charles , Gautier Thomas , Lagrost Laurent , Masson David
Published: April 2013

Objective—

Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that are highly expressed in macrophages and regulate lipid homeostasis and inflammation. Among putative LXR target genes, lysophosphatidylcholine acyltransferase 3 (LPCAT3) involved in the Lands cycle controls the fatty acid composition at the sn-2 position of glycerophospholipids and, therefore, the availability of fatty acids, such as arachidonic acid (AA), used for eicosanoid synthesis. The aim of our study was to determine whether LXRs could regulate the Lands cycle in human macrophages, to assess the consequences in terms of lipid composition and inflammatory response, and to work out the relative contribution of LPCAT3 to the observed changes.

Approach and Results—

Transcriptomic analysis revealed that LPCAT3 was upregulated by LXR agonists in human macrophages. Accordingly, LXR stimulation significantly increased lysophospholipid acyltransferase activity catalyzed by LPCAT3. Lipidomic analysis demonstrated that LXR activation increased the AA content in the polar lipid fraction, specifically in phosphatidylcholines. The LXR-mediated effects on AA distribution were abolished by LPCAT3 silencing, and a redistribution of AA toward the neutral lipid fraction was observed in this context. Finally, we observed that preconditioning of human macrophages by LXR agonist treatment increased the release of arachidonate-derived eicosanoids, such as prostaglandin E
2
and thromboxane after lipopolysaccharide stimulation, with a significant attenuation by LPCAT3 silencing.

Conclusions—

Altogether, our data demonstrate that the LXR-mediated induction of LPCAT3 primes human macrophages for subsequent eicosanoid secretion by increasing the pool of AA, which can be mobilized from phospholipids.