bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of glutathione S‐transferase pi 1 expression and gene promoter methylation in Moroccan patients with urothelial bladder cancer
Authors: Hadami Khaoula , Dakka Nadia , Bensaid Mounia , El Ahanidi Hajar , Ameur Ahmed , Chahdi Hafsa , Oukabli Mohamed , Al Bouzidi Abderrahmane , Attaleb Mohammed , El Mzibri Mohammed 
Published: July 2018

AbstractBackgroundGlutathione S‐transferase pi 1 (GSTP1) is a cytosolic detoxifying enzyme that protects cells against deleterious effects of oxidative stress. Deregulated expression of GSTP1 protein and aberrant promoter methylation of GSTP1 gene were reported in various human tumors and were shown to be involved in the molecular pathway for cancer development.Aims and methodsIn this study, we aimed to determine the expression status of GSTP1 in relation to its gene promoter methylation in Moroccan population of 30 bladder cancer (BC) patients and in two noncancerous bladder tissues used as controls. GSTP1 expression was assessed by immunohistochemistry and GSTP1 gene promoter methylation status was studied by methylation‐specific PCR (MS‐PCR).ResultsGlutathione S‐transferase pi 1 was expressed in the two normal tissues. In BC cases, GSTP1 expression was strong in 23.33% (7/30), moderate in 60% (18/30), and weak in 13.33% (4/30) of cases, while GSTP1 was not expressed in one cancer case (3.33%). Variability of GSTP1 expression does not correlate with high‐grade cancer or invasive‐stage (p > 0.05). No GSTP1 gene promoter methylation was detected in all control and cancer cases.ConclusionOur data suggest that GSTP1 expression is not associated with BC development, limiting its use as a biomarker for BC management in Morocco. Moreover, difference in GSTP1 expression among BC cases is not due to GSTP1 promoter methylation.
Analog and digital signal processing method using multi‐time‐over‐threshold and FPGA for PET
Authors: Kim Kyu Bom , Choi Yong , Jung Jiwoong , Lee Sangwon , Choe Hyeok‐jun , Leem Hyun Tae 
Published: July 2018

PurposeThe goal of this study was to develop an analog and digital signal processing method using multi‐time‐over‐threshold (MTOT) and field programmable gate arrays (FPGAs) to extract PET event information by using the internal clock of FPGA (~350 MHz), without ADC and TDC.MethodsThe PET detector modules were composed of a 4 × 4 matrix of 3 × 3 × 20 mm3 LYSO and 4 × 4 SiPM array. Output charge signals of PET detector modules were amplified and fed into four comparators to generate trigger signals. The energy of the detected gamma ray was calculated by integrating the digitized pulse and the arrival time was determined from the time stamp of the lowest trigger signal by FPGA. The data packet containing energy, time, and position information was stored in list mode on the host computer.ResultsThe performance of analog and digital signal processing circuits using MTOT method and FPGA was evaluated by measuring energy and time resolution of the proposed method and the values were 19% and 900 ps, respectively.ConclusionThis study demonstrated that the proposed MTOT method consisting of only FPGA without ADC and TDC could provide a simple and cost‐effective analog and digital signal processing system for PET.
Micromechanical approach to effective viscoelastic properties of micro‐fractured geomaterials
Authors: Aguiar Cássio B. , Maghous Samir 
Published: July 2018

SummaryThe aim of this paper is to formulate a micromechanics‐based approach to non‐aging viscoelastic behavior of materials with randomly distributed micro‐fractures. Unlike cracks, fractures are discontinuities that are able to transfer stresses and can therefore be regarded from a mechanical viewpoint as interfaces endowed with a specific behavior under normal and shear loading. Making use of the elastic‐viscoelastic correspondence principle together with a Mori‐Tanka homogenization scheme, the effective viscoelastic behavior is assessed from properties of the material constituents and damage parameters related to density and size of fractures. It is notably shown that the homogenized behavior thus formulated can be described in most cases by means of a generalized Maxwell rheological model. For practical implementation in structural analyses, an approximate model for the isotropic homogenized fractured medium is formulated within the class of Burger models. Although the approximation is basically developed for short‐term and long‐term behaviors, numerical applications indicate that the approximate Burger model accurately reproduce the homogenized viscoelastic behavior also in the transient conditions.
Evidence for lineage continuity between early serous proliferations (ESPs) in the Fallopian tube and disseminated high‐grade serous carcinomas
Authors: Soong Thing Rinda , Howitt Brooke E , Miron Alexander , Horowitz Neil S , Campbell Frank , Feltmate Colleen M , Muto Michael G , Berkowitz Ross S , Nucci Marisa R , Xian Wa , Crum Christopher P 
Published: July 2018

AbstractThe distal Fallopian tube is a site of origin for many ‘ovarian’ high‐grade serous carcinomas (HGSCs) with intraepithelial carcinomas (STICs) that share identical TP53 mutations with metastatic tumors. TP53 mutation‐positive early serous proliferations (ESPs) comprise a spectrum including p53 signatures and serous tubal intraepithelial lesions (STILs) and are not considered malignant; however, ESPs are often the only abnormality found in Fallopian tubes of women with metastatic HGSC. The purpose of this study was to determine if a relationship exists between isolated ESPs and concurrent metastatic HGSCs in the absence of STIC. Fallopian tubes from 32 HGSCs without a co‐existing STIC/HGSC in the endosalpinx were exhaustively sectioned. The presence of either STIC/HGSC or ESP in the endosalpinx was documented and DNA from tissues containing ESPs, concurrent HGSC, and control epithelia were interrogated for TP53 mutations by targeted amplicon‐based sequencing with average coverage reads >4000 across DNA replicate samples. Serial sectioning revealed a previously unrecognized STIC/HGSC in 3 of 32 (9.3%) and ESPs in 13 (40.6%). Twelve contained TP53 mutations. Nine (75%) shared identical TP53 mutations with concurrent HGSCs, four at high (≥ 5%) and five at low (< 5%) allele frequency. All control epithelia were TP53 mutation‐negative. This study, for the first time, indicates lineage identity between ESPs in the distal tube and some metastatic HGSCs via a shared site‐specific TP53 mutation. It supports a novel serous carcinogenic sequence in which an ESP could eventually culminate in a metastatic serous cancer via ‘precursor escape’ and would explain the apparent sudden onset of cancers without co‐existing STICs. This paradigm for serous cancer development underscores the likelihood that multiple precursor types in the Fallopian tube contribute to serous cancer development with implications for the evolution, pathologic classification, and prevention of this lethal malignancy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Population Pharmacokinetic/Pharmacodynamic Analysis of Nociceptive Pain Models Following an Oral Pregabalin Dose Administration to Healthy Subjects
Authors: van Esdonk Michiel J. , Lindeman Ian , Okkerse Pieter , de Kam Marieke L. , Groeneveld Geert J. , Stevens Jasper 
Published: July 2018

A battery of pain models can be used in clinical trials to investigate the efficacy and to establish the concentration‐effect relationship of novel analgesics. This study quantified the pharmacokinetics (PK) of pregabalin after a single oral dose of 300 mg and the pharmacodynamics (PD) on the pain tolerance threshold (PTT) of the cold pressor, electrical stimulation, the pressure pain model, and on the pain detection threshold of a contact heat pain model. The PK were best described using a one‐compartment model with lag time, linear absorption, and linear elimination. The PTT of the cold pressor showed a negative linear decrease over time without pregabalin. A linear drug effect was identified on the PTT of the cold pressor test and an on/off effect for the electrical stimulation PTT. No PK/PD relationship could be identified on the pressure pain and heat pain test. Citation:
A Semi‐Mechanistic Population Pharmacokinetic Model of Nusinersen: An Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy
Authors: Biliouris Konstantinos , Gaitonde Puneet , Yin Wei , Norris Daniel A. , Wang Yanfeng , Henry Scott , Fey Robert , Nestorov Ivan , Schmidt Stephan , Rogge Mark , Lesko Lawrence J. , Trame Mirjam N. 
Published: July 2018

A pharmacokinetic (PK) model was developed for nusinersen, an antisense oligonucleotide (ASO) that is the first approved treatment for spinal muscular atrophy (SMA). The model was built with data from 92 nonhuman primates (NHPs) following intrathecal doses (0.3–7 mg) and characterized the PK in cerebrospinal fluid (CSF), plasma, total spinal cord, brain, and pons. The estimated volumes were 13.6, 937, 4.5, 53.8, and 2.11 mL, respectively. Global sensitivity analysis demonstrated that the CSF‐to‐plasma drug distribution rate (0.09 hour−1) is a major determinant of the maximum nusinersen concentration in central nervous system (CNS) tissues. Physiological age‐based and body weight‐based allometric scaling was implemented with exponent values of −0.08 and 1 for the rate constants and the volume of distribution, respectively. Simulations of the scaled model were in agreement with clinical observations from 52 pediatric phase I PK profiles. The developed model can be used to guide the design of clinical trials with ASOs.
RRep: A composite index to assess and test rater precision
Authors: Vanacore Amalia , Pellegrino Maria Sole 
Published: July 2018

AbstractIn subjective evaluation systems, raters act as measurement instruments providing useful evaluations for taking strategic and/or operational decisions. The assessment of rater evaluative ability in terms of accuracy and precision is of critical importance since rater unreliability may compromise the quality of the decision‐making process. The focus of this paper is on rater precision: we propose a novel composite index to assess the rater ability to provide evaluations repeatable over time and reproducible over scales. The extent of rater precision is qualified via a nonparametric benchmarking procedure. The properties of both proposed index and benchmarking procedure have been analysed via a Monte Carlo simulation study.
Factors influencing hunter flush success of three small game species
Authors: Rhoden Cody M. , Orange Jeremy P. , Tanner Evan P. , Baxley Danna L. , Morgan John J. , Robinson Ben A. 
Published: July 2018

ABSTRACTEncounter rates may have multifaceted effects on population dynamics, hunter satisfaction, and hunter retention. However, there is currently a lack of knowledge pertaining to those factors affecting small game flush rates. In an effort to address this paucity of information, we investigated factors that may affect flush rates of 3 small game species: ruffed grouse (Bonasa umbellus; hereafter, grouse), northern bobwhite (Colinus virginianus; hereafter, bobwhite), and rabbit (Sylvilagus spp.). From 2003 to 2015, we collected cooperator hunting logs for 3,948 grouse hunts, 19,301 rabbit hunts, and 4,798 bobwhite hunts in Kentucky, USA. Hunting success was defined as the number of grouse, rabbit, or bobwhite coveys flushed by a hunting party. We used an information theoretic approach to model variables that may explain variation in hunting success. The number of hunters within a party explained the greatest amount of variation in hunting success for all species, with a positive relationship between the number of hunters and success. Similarly, for grouse and rabbit, we observed a positive relationship between the number of dogs in a party and hunting success. Weather variables and annual abundance indices were not supported in any competing models explaining hunting success, suggesting a possible scale mismatch related to these broad‐scale data and more localized conditions experienced by hunting parties. Our research indicates that increasing hunting party size through the addition of hunters and dogs was a unifying influence on increasing hunting success (likely through increased hunting corridors) across small game species. This information can be useful for agencies seeking to increase or maintain support for small game hunters in the future. © 2018 The Wildlife Society.
Element Distribution in the Silicomanganese Production Process
Authors: Ma Yan , Moosavi-Khoonsari Elmira , Kero Ida T. , Tranell Gabriella M. 
Published: July 2018

Abstract
A pilot scale, silicomanganese alloy production campaign was performed in a 440 kVA, single phase electric furnace in order to establish an overview of the minor- and trace element contents in process input raw materials and their distribution in the resulting primary and secondary products. Samples of the in-going raw materials (manganese ore, coke, quartzite, and high carbon ferromanganese slag) and the out-going products (silicomanganese alloy, silicomanganese slag, and dust) were analyzed by inductively coupled plasma mass spectrometry. The distribution of 51 elements between the product phases was discussed in terms of their boiling temperatures, Gibbs energies of oxidation and activity coefficients of elements in the metal. A thermochemical simulation using the thermochemical software FactSage 7.1 was also carried out in order to model element phase distribution between the alloy, slag, and dust/gas. The correlation between the model and experimental element concentrations in the silicomanganese slag and dust is fair for most elements. However, in the metal phase, fewer elements show good correlation between modeled results and measured experimental concentrations. The discrepancy could be explained by a lack of accurate thermodynamic descriptions for several minor species in the database.
A novel multi-level evaluation approach for human-coupled IoT applications
Authors: Seok Moon Gi , Park Daejin 
Published: July 2018

AbstractThe recent emerging trend to promote the harmonious interactions between human and smart objects in Internet of Things (IoT) applications has led to the rising demand for the comprehensive exploration of associated IoT design spaces, considering system-, network-, and human-level perspectives. The traditional design approach of networked smart objects tends to ignore the effects caused by human interactions so that the existing approach has the limited capability in joint system/network/human multi-level exploration. In this paper, we propose a high-level system modeling and multi-level simulation approach for microsystem models to interoperate with high-level models in the human-level perspective and to provide comprehensive co-exploration. The high-level system modeling enables one to abstract the detailed operations of hardware platforms using power and timing data obtained by the proposed high-level state-based profiling method and using the event-driven modeling concept. For the event-driven system modeling, we utilize the discrete-event system specification (DEVS) to support scalable model-driven prototyping. To represent the coupled relationship of network-level system activity and human-level interactions between node systems and humans, we employ a general-purpose network simulator to model the operation and communication of network modules in smart objects and developed agent-based human behavioral models. For the co-simulation of multi-level models, we designed a distributed simulation platform to enable the interoperation between the DEVS simulator and the network simulator using a runtime infrastructure. The proposed modeling and simulation approach is applied for the multi-level evaluation of a smart museum application to estimate the effect of energy-efficiency policies.
Is patient factor more important than surgeon-related factor in sepsis prevention in colorectal surgery?
Authors: Weledji Elroy Patrick 
Published: July 2018

ABSTRACT

Background:
Postoperative infection is an important complication of colorectal surgery and continued efforts are needed to minimize the risk of surgical site infection (SSI). Sepsis prevention in colorectal surgery depends upon the degree of contamination of the peritoneal cavity (disease factor), the preoperative status of the patient (patient factor) and surgical technique (surgeon factor). Immune response and metabolic regulation are highly integrated as minor operations may stimulate the immune response while the effect of major surgery is immunosuppression. The article debates the relative contributions and impact of patient and surgeon-related factors on sepsis prevention in colorectal surgery.

Methods:
A retrospective literature review of published studies on sepsis prevention in colorectal surgery, bacteria-host interactions and the effects of immune deficiency, life-style (smoking, alcohol abuse) and non-steroidal anti-inflammatory drugs on the outcome of colorectal surgery.

Results:
The most important factor in determining postoperative sepsis is the presence of viable organisms in the surgical field prior to wound closure. Inter-individual variation in the pattern of mediator release and of end-organ responsiveness may play a significant role in determining the initial physiological response to major sepsis and this in turn may be a key determinant of outcome. Sepsis source control failure in colorectal surgery are more likely in patients with delayed (>24 h) procedural intervention (Patient/surgeon factor), higher severity of illness - the Acute Physiology, Age and Chronic Health Care Evaluation score (APACHE >15 (patient/disease factor), advanced age- >70yrs (patient factor), co-morbidity (patient factor), poor nutritional status (patient factor) and a higher degree of peritoneal involvement – Mannheim peritonitis index (MPI) score (disease factor). It would be heralded by persistent or recurrent intra-abdominal infection, anastomotic failure or fistula formation.

Conclusions:
The most important prognostic factors in emergency colorectal surgery are the preoperative status, age and faecal peritonitis. Thus, peritoneal sepsis is seldom the sole cause of death, but compounds coincidental cardiovascular, respiratory or renal pathology. The empiric choice of the surgical technique/procedure is predominantly determined by the patient status and the disease. The patient factor is thus more important than the surgeon factor in the prognosis of sepsis in emergency colorectal surgery but surgeon-related factors can influence the morbidity and mortality from sepsis in both elective and emergency colorectal surgery.

Highlights:
Anomalous blocking over Greenland preceded the 2013 extreme early melt of local sea ice
Authors: Ballinger Thomas J. , Hanna Edward , Hall Richard J. , Cropper Thomas E. , Miller Jeffrey , Ribergaard Mads H. , Overland James E. , Høyer Jacob L. 
Published: July 2018

ABSTRACTThe Arctic marine environment is undergoing a transition from thick multi-year to first-year sea-ice cover with coincident lengthening of the melt season. Such changes are evident in the Baffin Bay-Davis Strait-Labrador Sea (BDL) region where melt onset has occurred ~8 days decade−1 earlier from 1979 to 2015. A series of anomalously early events has occurred since the mid-1990s, overlapping a period of increased upper-air ridging across Greenland and the northwestern North Atlantic. We investigate an extreme early melt event observed in spring 2013. (~6σ below the 1981–2010 melt climatology), with respect to preceding sub-seasonal mid-tropospheric circulation conditions as described by a daily Greenland Blocking Index (GBI). The 40-days prior to the 2013 BDL melt onset are characterized by a persistent, strong 500 hPa anticyclone over the region (GBI >+1 on >75% of days). This circulation pattern advected warm air from northeastern Canada and the northwestern Atlantic poleward onto the thin, first-year sea ice and caused melt ~50 days earlier than normal. The episodic increase in the ridging atmospheric pattern near western Greenland as in 2013, exemplified by large positive GBI values, is an important recent process impacting the atmospheric circulation over a North Atlantic cryosphere undergoing accelerated regional climate change.
Health Care Student Perceptions of Societal Vulnerability to Disasters in the Context of Population Aging
Authors: Lucas Peter , Annear Michael , Harris Wayne , Eyles Helen , Rotheram Auston 
Published: July 2018

ABSTRACTObjectiveThis paper reports on undergraduate health care students’ perception of societal vulnerability to disasters in the context of population aging. Forecast increases in extreme weather events are likely to have a particularly devastating effect on older members of the community.MethodsUndergraduate paramedicine and nursing students were surveyed using the Perceptions of Ageing and Disaster Vulnerability Scale (PADVS) to determine their views on the risks posed to older members of the community by disasters. Data analysis included a comparison of subscales relating to isolation, health system readiness, declining function, and community inclusiveness.ResultsStudents reported a moderate level of concern about disaster vulnerability. Students who had previously completed another university degree reported significantly higher levels of concern than those without a prior degree. Australian students reported lower concern about societal vulnerability compared to a previously reported cohort of Japanese students.ConclusionOur study suggests current education of future health care students does not promote adequate levels of awareness of the health-related challenges posed by disasters, particularly among older members of the community. Without addressing this gap in education, the risk of negative outcomes for both unprepared first responders and older members of the community is significant. (Disaster Med Public Health Prep. 2019;13:449-455)