bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Implications and Correlates of Q Waves in Patients With ST‐Elevation Myocardial Infarction Treated With Fibrinolysis: Observations from the CLARITY‐TIMI 28 Trial
Authors: Waks Jonathan W. , Sabatine Marc S. , Cannon Christopher P. , Morrow David A. , Gibson C. Michael , Wiviott Stephen D. , Giugliano Robert P. , Sloan Sarah , Scirica Benjamin M.
Published: January 2014

Background

The relationships between Q waves that appear during the acute phase of ST‐elevation myocardial infarction (STEMI), clinical characteristics, ST‐segment resolution (STRes), and clopidogrel therapy in patients treated with fibrinolysis are not well described.

Hypothesis

We hypothesized that Q waves would be associated with less successful reperfusion and increased cardiovascular events.

Methods

In the CLARITY‐TIMI 28 trial, 3491 STEMI patients treated with fibrinolysis were randomized to clopidogrel or placebo. Electrocardiograms were evaluated for STRes post‐fibrinolysis and the presence of pathologic Q waves during the index hospitalization in 3322 patients.

Results

Q waves were identified in 2045 patients (61.6%) prior to discharge and were associated with increased odds of congestive heart failure (CHF) (adjusted odds ratio [ORadj]: 2.10, P = 0.002) or the composite of cardiovascular death/CHF at 30 days (ORadj: 2.08, P ≤ 0.001). Q waves were associated with lower odds of Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 to 3 (ORadj: 0.78, P = 0.028), TIMI myocardial perfusion grade 3 (ORadj: 0.83, P = 0.029), and complete STRes at 90 minutes (ORadj: 0.80, P = 0.030). Patients with both a Q wave and incomplete STRes 90 minutes after fibrinolysis were at higher risk for cardiovascular death or CHF (11.1%) than patients with no Q wave and at least partial STRes (1.9%). Overall, clopidogrel tended to be equally or more effective in patients without Q waves compared to those with Q waves.

Conclusions

Among STEMI patients treated with fibrinolysis, evaluating for Q waves prior to discharge is a simple method of assessing for less successful reperfusion and an increased risk of adverse 30‐day cardiovascular outcomes. The combination of Q waves and 90‐minute STRes allows additional risk refinement.
Diagnostic Performance of Copeptin in Patients With Acute Nontraumatic Chest Pain: BWH‐TIMI ED Chest Pain Study
Authors: Sukul Devraj , Bonaca Marc P. , Ruff Christian T. , Kosowsky Joshua , Conrad Michael , Murphy Sabina A. , Sabatine Marc S. , Jarolim Petr , Morrow David A.
Published: January 2014

Background

Arginine‐vasopressin (AVP) is an acute marker of physiologic stress. Copeptin is the C‐terminal fragment of vasopressin precursor hormone that is more easily measured than AVP. Studies assessing the utility of copeptin in the diagnosis of myocardial infarction (MI) have demonstrated mixed results.

Hypothesis

The aim of this study was to test the hypothesis that copeptin improves diagnostic performance when added to troponin for detecting MI in patients presenting to the emergency department with nontraumatic chest pain.

Methods

We measured copeptin, local cardiac troponin I (local cTnI), and a contemporary sensitive cardiac troponin I (sensitive cTnI) at presentation and serially in patients who presented with acute chest pain. A copeptin cutoff of 14 pmol/L was utilized.

Results

MI was diagnosed in 25.7% of patients. Noncoronary acute cardiopulmonary causes of chest pain occurred in 12.8%. Patients with MI had significantly higher copeptin levels than patients with noncardiac chest pain (P < 0.001). The area under the receiver operating characteristic curve (AUC) for copeptin was 0.60 (95% confidence interval: 0.54‐0.66), significantly less than the AUC for local cTnI (0.92) or sensitive cTnI (0.96). The combination of copeptin with either the local or sensitive troponin assay (c‐statistics 0.92 and 0.95, respectively) did not significantly improve the AUC as compared to either troponin assay alone. This finding persisted in the subgroup of early presenters (≤6 hours from symptom onset).

Conclusions

Copeptin did not improve the diagnostic performance for detecting MI when used alone or in combination with a contemporary sensitive cTnI assay, though our cohort had relatively few early presenters.
A comparative study on perceptual evaluations of sports shoe exterior colors in Taiwan
Authors: Shieh Meng‐Dar , Yeh Yu‐En
Published: January 2014

We investigated consumer psychology, perception, and aesthetics in relation to sports shoe colors in Taiwan. Semantic differential rating (three emotional adjective pairs) and preference rating questionnaires were distributed among 512 university students to investigate whether their responses to various sports shoe colors differed. The results show that black is one of the most popular colors for sports shoes. The participants preferred designs that incorporated white as the secondary color and disliked those that featured green as the main and secondary colors. In addition, designs incorporating black or red as the main color with a bright color as the secondary color were considered modern. Black and white designs were perceived to be more suited to formal occasions. Furthermore, when the area of the main color exceeded that of the secondary color, the participants perceived a strong sense of simplicity, unless the colors were blue and green. The participants preferred two‐color over one‐color designs, and three‐color designs had a higher correlation with participant preferences. Women required more time than men to evaluate a sample. The men typically examined the samples from a frontal angle, whereas the women focused on the sides of the sample. The scoring scale was polarized (e.g., highest score for modern was −10 and 10 for retro), rendering the values of the Pearson correlation coefficient analysis comparatively low, resulting in weak correlations between variables. However, the relative differences of these values retained referential value regarding objective quantification. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 178–193, 2015
Refined CIECAM02 for bright surround conditions
Authors: Park YungKyung , Luo Ming Ronnier , Li Chang Jun , Kwak Youngshin
Published: January 2014

Displays such as mobile phones are viewed under surround conditions that vary from dark night to bright sunlight. The overall goal of this study is to test the appropriateness of CIECAM02 for mobile displays, and modify it according to any insufficiency found. Firstly, the testing of CIECAM02 is described using the visual data from 2‐inch display of three achromatic backgrounds (gray, black, and white), and three surround conditions (dark, dim, and average). Secondly, CIECAM02 was tested under four surround conditions (dark, dim, average, and bright), and three displays (2‐, 4‐, and 7‐inch), with only the gray background used, to focus more on the surround conditions. Those twelve experimental phases were used to refine CIECAM02, considering the surround factors. The surround parameters (c, F, and NC) were optimized, and Ncb was modified from the CIECAM02; the modified model is named MobileCAM‐v1. Colourfulness prediction by MobileCAM‐v1 has been improved, especially for a black background under average surround condition. A further refined version of CIECAM02, MobileCAM‐v2, was developed, for mobile displays viewed under different surround conditions. A set of equations based on surrounding conditions was first derived, to be able to accurately define surround parameters. The MobileCAM‐v2 model gave the largest improvement in brightness, followed by lightness, and with colourfulness the smallest. The improvement is significant for bright surround conditions, improving the performance of CIECAM02 in predicting the visual results. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 114–124, 2015
An OAM function to improve the packet loss in MPLS‐TP domains for prioritized QoS‐aware services
Authors: Rodríguez‐Pérez Francisco‐Javier , González‐Sánchez José‐Luis , Carmona‐Murillo Javier , Cortés‐Polo David
Published: January 2014

The emergence of new kinds of applications and technologies (e.g., data‐intensive applications, server virtualization, and big data technology) has led to a higher utilization of network resources. These services imply increased bandwidth consumption and unexpected congestions, especially in backbones. In this article, a novel proposal is studied with the aim of improving the performance of prioritized forwarding equivalence classes in congested Multiprotocol Label Switching Transport Profile (MPLS‐TP) domains. The congestion impact on those QoS‐aware services that require high reliability and low delay is analyzed. A new policy has been implemented on MPLS‐TP, which is a technology that provides QoS by means of flow differentiation in the Internet backbones. The proposal is known as Gossip‐based local recovery policy and is offered as an operation, administration, and management function to allow local recovery of lost traffic for MPLS‐TP privileged forwarding equivalence classes. In order to fulfill the requirements for implementation on MPLS‐TP, a minimum set of extensions to resource reservation protocol traffic engineering has also been proposed to provide self‐management capable routes. Finally, we have carried out a performance improvement measurement by means of an analytical model and simulations. Copyright © 2014 John Wiley & Sons, Ltd.
A multiplex single nucleotide polymorphism genotyping method using ligase‐based mismatch discrimination and CE‐SSCP
Authors: Choi Woong , Shin Gi Won , Hwang Hee Sung , Pack Seung Pil , Jung Gyu Yong , Jung Gyoo Yeol
Published: January 2014

Accuracy, simplicity, and cost‐effectiveness are the most important criteria for a genotyping method for SNPs compatible with clinical use. One method developed for SNP genotyping, ligase‐based discrimination, is considered the simplest for clinical diagnosis. However, multiplex assays using this method are limited by the detection method. Although CE has been introduced as an alternative to error prone microarray‐based detection, the design process and multiplex assay procedure are complicated because of the DNA size‐dependent separation principle. In this study, we developed a simple and accurate multiplex genotyping method using reaction condition‐optimized ligation and high‐resolution CE‐based SSCP. With this high‐resolution CE‐SSCP system, we are able to use similar‐sized probes, thereby eliminating the complex probe design step and simplifying the optimization process. We found that this method could accurately discriminate single‐base mismatches in SNPs of the tp53 gene, used as targets for multiplex detection.
Identification of somatic alterations in stage I lung adenocarcinomas by next‐generation sequencing
Authors: Zhao Yuda , Yang Jie , Chen Zhaoli , Gao Zhibo , Zhou Fang , Li Xiangchun , Li Jiagen , Shi Susheng , Feng Xiaoli , Sun Nan , Yao Ran , Zhou Chengcheng , Chang Sheng , Li Miao , Zhou Yong , Li Lin , Zhang Xiuqing , He Jie
Published: January 2014

Adenocarcinoma is the most common type of lung cancer. Somatic mutations in the early stage of this disease have a tight relationship with tumor initiation and potentially activate downstream pathways that are implicated in tumor progression. In this study, we performed whole genome and exome sequencing of tumor and adjacent normal tissue from 10 patients with stage I lung adenocarcinoma. EGFR (4/10 tumors), BCHE (3/10), and TP53 (2/10) were identified recurrently with validated tumor‐specific non‐synonymous mutations; and the remaining mutations were specific to individual tumors. Computational methods were used to evaluate the potential effect of non‐synonymous mutations on protein function, and putative driver mutation in genes such as SDK1 was predicted. Cell adhesion was the most enriched biological process in gene set analysis using the DAVID database. Copy number amplification at 12q15, which includes MDM2, was identified as a recurrent somatic alteration in 4 of 10 tumors. These findings provided additional information for understanding early‐stage lung adenocarcinomas. © 2014 Wiley Periodicals, Inc.
Effects of fault‐zone architecture on earthquake magnitude and gas leakage related to CO2 injection in a multi‐layered sedimentary system
Authors: Rinaldi Antonio P. , Jeanne Pierre , Rutqvist Jonny , Cappa Frédéric , Guglielmi Yves
Published: January 2014

The presence of fluid within a fault zone can cause overpressure and trigger earthquakes. In this work, we study the influence of fault‐zone architecture on pore pressure distribution and on the resulting fault reactivation caused by CO2 injection. In particular, we investigate the effect of the variation and distribution of lithological and rock physical properties within a fault zone embedded in a multi‐layer sedimentary system. Through numerical analysis, we compare several models where the complexity of the fault‐zone architecture and different layers (such as caprock and injection reservoir) are incrementally included. Results show how the presence of hydraulic and mechanical heterogeneity along the fault influences the pressure diffusion, as well as the effective normal and shear stress evolution. Hydromechanical heterogeneities (i) strengthen the fault zone resulting in earthquakes of small magnitude, and (ii) impede fluid migration upward along the fault. We also study the effects of the caprock and aquifer thickness on the resulting induced seismicity and CO2 leakage, both in heterogeneous and homogeneous fault zones. Results show that a thin caprock or aquifer allows smaller events, but a much higher percentage of leakage through the caprock and into the upper aquifer. The amount of leakage reduces drastically in the case of a multi‐caprock, multi‐aquifer system.
The COP9 signalosome is a repressor of replicative stress responses and polyploidization in the regenerating liver
Authors: Panattoni Martina , Maiorino Laura , Lukacs Anna , Zentilin Lorena , Mazza Davide , Sanvito Francesca , Sitia Giovanni , Guidotti Luca G. , Pardi Ruggero
Published: January 2014

Aberrant DNA replication induced by deregulated or excessive proliferative stimuli evokes a “replicative stress response” leading to cell cycle restriction and/or apoptosis. This robust fail-safe mechanism is eventually bypassed by transformed cells, due to ill-defined epistatic interactions. The COP9 signalosome (CSN) is an evolutionarily conserved regulator of cullin ring ligases (CRLs), the largest family of ubiquitin ligases in metazoans. Conditional inactivation of the CSN in several tissues leads to activation of S- or G2-phase checkpoints resulting in irreversible cell cycle arrest and cell death. Herein we ablated COPS5, the CSNs catalytic subunit, in the liver, to investigate its role in cell cycle reentry by differentiated hepatocytes. Lack of COPS5 in regenerating livers causes substantial replicative stress, which triggers a CDKN2A-dependent genetic program leading to cell cycle arrest, polyploidy, and apoptosis. These outcomes are phenocopied by acute overexpression of c-Myc in COPS5 null hepatocytes of adult mice. Conclusion: We propose that combined control of proto-oncogene product levels and proteins involved in DNA replication origin licensing may explain the deleterious consequences of CSN inactivation in regenerating livers and provide insight into the pathogenic role of the frequently observed overexpression of the CSN in hepatocellular carcinoma. (Hepatology 2014;59:2331–2343)
Threatening communication: A qualitative study of fear appeal effectiveness beliefs among intervention developers, policymakers, politicians, scientists, and advertising professionals
Authors: Peters Gjalt‐Jorn Y. , Ruiter Robert A. C. , Kok Gerjo
Published: January 2014

Threatening communication is a widely applied method in behavior change interventions, which at the same time has been heavily criticized in the psychological literature. The current paper describes a study of the reasons for this persistent wide application of threatening communication. We conducted qualitative interviews with 33 key actors in behavior change intervention development in The Netherlands. Specifically, we interviewed intervention developers, policymakers, politicians, scientists, and advertising professionals. The interviews were transcribed and subsequently coded using NVivo. We found that participants most closely involved with the actual intervention development were generally convinced that threatening information was to be prevented, but often did not understand the exact processes involved. They were often under the impression that rather than a potent efficacy enhancing element, a behavioral suggestion would suffice to prevent threatening communication from backfiring. As participants were further removed from the actual intervention development, they generally tended to be more in favor of threatening communication. The main reasons for use of threatening information were to attract attention or prompt self‐reflection through confrontation, because target population members were assumed to like threatening information and respond rationally to increased risk perceptions by changing their behavior, or simply because no alternatives were available. In addition, intervention developers frequently had to deal with supervisors or funders who preferred threatening communication. Thus, when communicating with practitioners, it seems fruitful to provide them with a toolbox of evidence‐based behavior change methods that promote adaptive, rather than maladaptive, behavior; to promote basing interventions on the most relevant behavioral determinants as identified by determinant analyses; and to equip intervention developers with the tools to persuade other key stakeholders that fear is a bad counselor.
The ethics of distress: Toward a framework for determining the ethical acceptability of distressing health promotion advertising
Authors: Brown Stephen L. , Whiting Demian
Published: January 2014

Distressing health promotion advertising involves the elicitation of negative emotion to increase the likelihood that health messages will stimulate audience members to adopt healthier behaviors. Irrespective of its effectiveness, distressing advertising risks harming audience members who do not consent to the intervention and are unable to withdraw from it. Further, the use of these approaches may increase the potential for unfairness or stigmatization toward those targeted, or be considered unacceptable by some sections of the public. We acknowledge and discuss these concerns, but, using the public health ethics literature as a guide, argue that distressing advertising can be ethically defensible if conditions of effectiveness, proportionality necessity, least infringement, and public accountability are satisfied. We do not take a broad view as to whether distressing advertising is ethical or unethical, because we see the evidence for both the effectiveness of distressing approaches and their potential to generate iatrogenic effects to be inconclusive. However, we believe it possible to use the current evidence base to make informed estimates of the likely consequences of specific message presentations. Messages can be pre‐tested and monitored to identify and deal with potential problems. We discuss how advertisers can approach the problems of deciding on the appropriate intensity of ethical review, and evaluating prospective distressing advertising campaigns against the conditions outlined.
The influence of item order on intentional response distortion in the assessment of high potentials: Assessing pilot applicants
Authors: Khorramdel Lale , Kubinger Klaus D. , Uitz Alexander
Published: January 2014

An experiment was conducted to investigate the effects of item order and questionnaire content on faking good or intentional response distortion. It was hypothesized that intentional response distortion would either increase towards the end of a long questionnaire, as learning effects might make it easier to adjust responses to a faking good schema, or decrease because applicants' will to distort responses is reduced if the questionnaire lasts long enough. Furthermore, it was hypothesized that certain types of questionnaire content are especially vulnerable to response distortion. Eighty‐four pre‐selected pilot applicants filled out a questionnaire consisting of 516 items including items from the NEO five factor inventory (NEO FFI), NEO personality inventory revised (NEO PI‐R) and business‐focused inventory of personality (BIP). The positions of the items were varied within the applicant sample to test if responses are affected by item order, and applicants' response behaviour was additionally compared to that of volunteers. Applicants reported significantly higher mean scores than volunteers, and results provide some evidence of decreased faking tendencies towards the end of the questionnaire. Furthermore, it could be demonstrated that lower variances or standard deviations in combination with appropriate (often higher) mean scores can serve as an indicator for faking tendencies in group comparisons, even if effects are not significant.
The family roles of siblings of people diagnosed with a mental disorder: Heroes and lost children
Authors: Sanders Avihay , Szymanski Kate , Fiori Kate
Published: January 2014

In order to cope with the diagnosis of mental illness in a family member, siblings may be forced to adjust their roles in the family. Taking into account the crucial role that some siblings play in caregiving for the mentally ill especially when the parents are no longer available, it is imperative to develop awareness of their unique needs and address them. Thirty‐three adult siblings of people diagnosed with a mental disorder completed the Role Behaviour Inventory (RBI) and a general questionnaire including open‐ended questions regarding the roles they played in their families of origin. Findings from the inventory and general questionnaire suggest that the well siblings score higher on two roles, the Hero and Lost Child, and lower on the Mascot and Scapegoat roles relative to a comparison group (N = 33). Being a sibling caregiver emerged as a risk factor to assume certain dysfunctional roles in the family. Implications for future research and therapy are discussed.
Profiles of psychological well‐being in a sample of Australian university students
Authors: Bhullar Navjot , Hine Donald W. , Phillips Wendy J.
Published: January 2014

The present study identified psychological well‐being profiles in a sample of Australian university students (N = 207, Mean age = 30.16 years;SD = 11.90). Respondents completed two measures: Ryff's (1989)Psychological Well‐Being(PWB) scale and Lovibond and Lovibond's (2002)Depression, Anxiety and Stress Scales‐21(DASS‐21) assessing their levels ofPWBand depression. Latent profile analysis was applied to six indices of positive functioning derived fromPWBscale:self‐acceptance,purpose in life,environmental mastery, positive relations with others,personal growthandautonomy. An optimal 5‐profile solution, reflecting significant incremental shifts from very low to very highPWB, was interpreted. As predicted, profile membership distinguished participants on depression. Importantly, profiles indicating moderate to very highPWB, particularly with the presence of above average autonomy, reported significantly lower levels of depression. Our results suggest prevention of, and treatment efficacy for, mental health problems may be improved by incorporating strategies that address positive functioning attributes, particularly associated with a sense of autonomy.
Closing the empathy gap in college students' judgments of end‐of‐life tradeoffs
Authors: Stephens Joseph D. W. , Neal Danielle S. , Overman Amy A.
Published: January 2014

When considering hypothetical end‐of‐life (EOL) scenarios involving 80‐year‐old intensive‐care unit patients, young adults are more likely than older adults to judge that shorter lifespan would be a fair trade in exchange for a more pleasant death. This result has been interpreted in terms of an empathy gap, in which individuals fail to relate to the affective states of others. If so, the effect should be reduced when young adults consider scenarios involving patients similar to themselves. The present study examined college students' willingness to trade healthy lifespan for better death in EOL scenarios involving 80‐year‐old and 22‐year‐old cancer victims. Results indicated students under 30 were less likely to trade lifespan in the 22‐year‐old scenarios, and were less likely to trade lifespan in either set of scenarios when the 22‐year‐old scenarios were presented first. The findings are consistent with an empathy gap account of judgments concerning EOL care.
Do Guyanese mothers' levels of warmth moderate the association between harshness and justness of physical punishment and preschoolers' prosocial behaviours and anger?
Authors: Roopnarine Jaipaul L. , Jin Bora , Krishnakumar Ambika
Published: January 2014

This study assessed the moderating role of Indo‐Guyanese mothers' warmth and affection on the associations between harshness and justness of physical punishment and prosocial behaviours and anger in preschoolers. One hundred and thirty‐nine rural Indo‐Guyanese mothers filled out Rohner's Parental Acceptance–Rejection (PARQ) and Physical Punishment Questionnaires (PPQ). Teachers provided assessments of children's prosocial behaviours and anger in preschool settings. Maternal warmth did not moderate the relationship between harshness of physical punishment and children's prosocial behaviours and anger, but it did moderate the relationship between justness of physical punishment and prosocial behaviours for sons as well as the association between justness of physical punishment and anger for daughters. In Caribbean societies where harsh punishment is normative, maternal warmth may work more effectively with justness, and not with harshness of physical punishment, to lower negative childhood behavioural outcomes.
RESIDENTIAL CARE FOR ABANDONED CHILDREN AND THEIR INTEGRATION INTO A FAMILY‐BASED SETTING IN UGANDA: LESSONS FOR POLICY AND PROGRAMMING
Authors: Walakira Eddy J. , Ochen Eric A. , Bukuluki Paul , Alllan Sue
Published: January 2014

This article describes a model of care for abandoned and neglected infants in need of urgent physical, social, and medical support as implemented by the Child's i Foundation, an international, nongovernmental organization operating in Uganda. The model discounts the need for long‐term care of young children within institutions and challenges the basis for intercountry adoption. Underpinned by the essentials of care continuum provided under the Uganda National Alternative Care Framework (Ministry of Gender, Labour and Social Development, 2012), the model emphasizes the need to effect the reintegration of the separated child within the family of his or her birth, or locally organize foster care or adoption. Highlighting policy and programming lessons, the model showcases a holistic approach to the problem and puts emphasis on interventions that are protective, promotional, and transformational and the use of a community‐oriented approach. The model offers guidance to both government and nongovernment actors in addressing the problems of child neglect and abandonment through the implementation of the alternative care framework.
Modulation of pain threshold by virtual body ownership
Authors: Martini M. , Perez‐Marcos D. , Sanchez‐Vives M.V.
Published: January 2014

Background

Appropriate sensorimotor correlations can result in the illusion of ownership of exogenous body parts. Nevertheless, whether and how the illusion of owning a new body part affects human perception, and in particular pain detection, is still poorly investigated. Recent findings have shown that seeing one's own body is analgesic, but it is not known whether this effect is transferable to newly embodied, but exogenous, body parts. In recent years, results from our laboratory have demonstrated that a virtual body can be felt as one's own, provided realistic multisensory correlations.

Methods

The current work aimed at investigating the impact of virtual body ownership on pain threshold. An immersive virtual environment allowed a first‐person perspective of a virtual body that replaced the own. Passive movement of the index finger congruent with the movement of the virtual index finger was used in the ‘synchronous’ condition to induce ownership of the virtual arm. The pain threshold was tested by thermal stimulation under four conditions: (1) synchronous movements of the real and virtual fingers; (2) asynchronous movements; (3) seeing a virtual object instead of an arm; and (4) not seeing any limb in real world.

Results

Our results show that, independently of attentional and stimulus adaptation processes, the ownership of a virtual arm per se can significantly increase the thermal pain threshold.

Conclusions

This finding may be relevant for the development and improvement of digital solutions for rehabilitation and pain treatment.
Power motion‐mode doppler signature: A useful tool for assessing middle cerebral artery stenosis
Authors: Kim Ji‐Sun , Lee Sang‐Wook , Eun Mi‐Yeon , Seo Woo‐Keun
Published: January 2014

Purpose

To identify power motion‐mode Doppler (PMD) patterns and assess their diagnostic value for the diagnosis of middle cerebral artery (MCA) stenosis.

Methods

Retrospective analyses of PMD data were performed for the identification of specific patterns related to MCA stenosis. The interrater reliability and the validity of these patterns were studied, using magnetic resonance angiography and conventional transcranial Doppler sonography as gold standards.

Results

Three PMD patterns were identified: the so‐called black‐hole, the white‐hole, and the diastolic‐band patterns in 58 among 178 MCAs. The mean flow velocity was significantly higher in arterial segments with the black‐hole patterns and lower in segments with the diastolic‐band pattern compared with the segments with normal patterns. The interrater reliability was good for each pattern. The black‐hole pattern or its combination with the white‐hole pattern showed the highest validity.

Conclusion

Despite some limitations, the black‐hole PMD pattern or its combination with the white‐hole pattern appeared as a reliable and valid marker for the diagnosis of MCA stenosis. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:348–354, 2014
Mitochondrial lactate metabolism is involved in antioxidative defense in human astrocytoma cells
Authors: Lemire Joseph , Auger Christopher , Mailloux Ryan , Appanna Vasu D.
Published: January 2014

Although lactate has traditionally been known to be an end product of anaerobic metabolism, recent studies have revealed its disparate biological functions. Oxidative energy production and cell signaling are two important roles assigned to this monocarboxylic acid. Here we demonstrate that mitochondrial lactate metabolism to pyruvate mediated by lactate dehydrogenase (LDH) in a human astrocytic cell line is involved in antioxidative defense. The pooling of this α‐ketoacid helps to detoxify reactive oxygen species, with the concomitant formation of acetate. In‐gel activity assays following blue native PAGE electrophoresis were utilized to demonstrate the increase in mitochondrial LDH activity coupled to the decrease in pyruvate dehydrogenase activity in the cells challenged by oxidative stress. The enhanced production of pyruvate with the concomitant formation of acetate in astrocytoma cells was monitored by high‐performance liquid chromatography. The ability of pyruvate to fend off oxidative stress was visualized by fluorescence microscopy with the aid of the dye 2′,7′‐dichlorodihydrofluorescein diacetate. Immunoblotting helped confirm the presence of elevated levels of LDH in cells exposed to oxidative stress, and recovery experiments were performed with pyruvate to diminish the oxidative burden on the astrocytoma. The acetate, generated as a consequence of the antioxidative attribute of pyruvate, was subsequently channeled toward the production of lipids, a process facilitated by the upregulation in activity of acetyl‐CoA synthetase and acetyl‐CoA carboxylase, as demonstrated by in‐gel activity assays. The mitochondrial lactate metabolism mediated by LDH appears to play an important role in antioxidative defence in this astrocytic system. © 2014 Wiley Periodicals, Inc.
Cytoreduction and heated intraperitoneal chemotherapy for colorectal cancer: Are we excluding patients who may benefit?
Authors: Rivard Justin D. , Mcconnell Yarrow J. , Temple Walley J. , Mack Lloyd A.
Published: January 2014

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are increasingly used to treat peritoneal carcinomatosis from colorectal cancer. It is still relatively unknown which poor prognostic factors to avoid in order to optimize patient selection for CRS + HIPEC.

Methods

Between February 2003 and October 2011, 68 consecutive colorectal cancer patients who underwent CRS + HIPEC with a complete cytoreduction were identified from a prospective database. Survival analysis was performed using the Kaplan–Meier method, with log rank testing of differences between groups. Multivariate analysis was conducted using Cox proportional hazard regression.

Results

Median follow‐up was 30.3 (range, 2–88) months amongst survivors. Patients with a peritoneal cancer index (PCI) of 10 or less showed improved survival over those with a PCI of 11 or higher (P = 0.03). No difference in survival was seen for the other potentially poor prognostic variables including lymph node status, synchronous peritoneal disease, peri‐operative systemic chemotherapy, and rectal cancer primary.

Conclusions

A low PCI was associated with improved survival. Complete CRS + HIPEC appears to result in similar survival outcomes regardless of delivery of peri‐operative systemic chemotherapy. Rectal origin, lymph node status, and synchronous peritoneal disease should not be used as an absolute exclusion criteria for CRS + HIPEC based on current data. J. Surg. Oncol. 2014 109:104–109. © 2013 Wiley Periodicals, Inc.
Epithelial‐to‐mesenchymal transition predicts prognosis in clinical gastric cancer
Authors: Murai Toshifumi , Yamada Suguru , Fuchs Bryan C. , Fujii Tsutomu , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Tanabe Kenneth K. , Kodera Yasuhiro
Published: January 2014

Background

Epithelial‐to‐mesenchymal transition (EMT) is considered to play an important role in cancer invasion and metastasis.

Methods

The mRNA levels of an epithelial marker (E‐cadherin), mesenchymal marker (vimentin), and Zeb‐1 were measured in 11 gastric cancer cell lines. Functional analysis was performed using Zeb‐1 knockdown. EMT status of 116 gastric cancer patients was determined by calculating the vimentin/E‐cadherin mRNA expression ratio in cancerous tissue and the correlation between EMT status, clinicopathological factors, prognosis, and Zeb‐1 were analyzed.

Results

Cell lines were classified as epithelial or mesenchymal. Zeb‐1 expression was significantly correlated with the mesenchymal phenotype. Treatment with Zeb‐1 siRNA also reduced the capacity to proliferate, migrate, and invade. Patients were classified as epithelial or mesenchymal by V/E ratio (vimentin/E‐cadherin ratio) and as Zeb‐1 low or high expression group. The mesenchymal group was significantly associated with diffuse type cancer and stage IV. On multivariate analysis, the EMT status (mesenchymal group) was an independent prognostic factor (P = 0.022). There was a significant correlation between the V/E ratio and Zeb‐1 expression (r = 0.73). Patients in Zeb‐1 high group had significantly poorer survival than those in low group (P = 0.0071).

Conclusions

EMT is a critical prognostic factor for gastric cancer. Zeb‐1 might be a promising therapeutic target. J. Surg. Oncol 2014; 109:684–689. © 2014 Wiley Periodicals, Inc.
Simultaneous quantification of l‐tetrahydropalmatine and its urine metabolites by ultra high performance liquid chromatography with tandem mass spectrometry
Authors: Xiao Weibin , Zhuang Xiaomei , Shen Guolin , Zhong Yuhuan , Yuan Mei , Li Hua
Published: January 2014

l‐tetrahydropalmatine (l‐THP) is a tetrahydroprotoberberine isoquinoline alkaloid that has been used as an analgesic agent in China for more than 40 years. Recent studies indicated its potential application in the treatment of drug addiction. In this study, a sensitive and rapid method using ultra high performance liquid chromatography with MS/MS was developed and validated for simultaneous quantitation of l‐THP and its desmethyl metabolites. Enzymatic hydrolysis was integrated into sample preparation to enable the quantitative determination of both free and conjugated metabolites. Chromatographic separation was achieved on an Agilent Poroshell 120 EC‐C18 column. Detection was performed by MS in the positive ion ESI mode. The calibration curves of the analytes were linear (r2 > 0.9936) over the concentration range of 1–1000 ng/mL with the lower limit of quantification at 1 ng/mL. The precision for both intra‐ and interday determinations was <8.97%, and the accuracy ranged from −8.74 to 8.65%. The recovery for all the analytes was >70% without significant matrix effect. The method has been successfully applied to the urinary excretion study of l‐THP in rats. The conjugates were found to be the major urine metabolites of the drug.
Filtrodynamics 2: Effects of Particle Size and Filter Type on Trans‐Filter Time‐Dependent Pressure Signals
Authors: Dufrechou Marie , Mignard Emmanuel , Drenski Michael F. , Reed Wayne F.
Published: January 2014

Filtrodynamic behavior of trans‐filter time‐dependent pressure signals ΔP(t) is determined for membrane and frit filters using latex spheres of varying diameter D. Membrane data are best interpreted via a time‐dependent, accreting filtration bed, based on Darcy's law. A single parameter, permeability k, describes each membrane/particle pair. For small particles, k increases with increasing D, then becomes D‐independent for large ones. Predictable behavior for polydisperse mixtures of small spheres is obtained. The mechanism and behavior of filtration for non‐membrane metallic frits is dramatically different, and better described by a previous “characteristic loading” model. Use of frit and membrane filters in series allowed monitoring each filter's separate response to particle accumulation.
Quantification of sweat gland volume and innervation in neuropathy: Correlation with thermoregulatory sweat testing
Authors: Loavenbruck Adam , Wendelschaefer‐Crabbe Gwen , Sandroni Paola , Kennedy William R.
Published: January 2014

Introduction: No study has correlated thermoregulatory sweat testing (TST) with histopathologic study of sweat glands (SGs) and SG nerve fibers (SGNFs). Methods: We studied 10 neuropathy patients in whom anhidrosis was found by TST and 10 matched controls. Skin biopsies were taken from both anhidrotic and sweating skin and immunohistochemical staining was done for nerves and basement membrane. For each biopsy, total tissue volume, total SG volume, and total SGNF length were measured. SGNF length per biopsy volume, SG volume per biopsy volume (SG%), and SGNF length per SG volume were calculated. Results: SGNF length per biopsy volume was reduced in anhidrotic site biopsies of patients compared with controls. SG% was decreased and SGNF length per SG volume increased in patients compared with controls. Conclusions: The results suggest a concomitant loss of SG volume and SGNF length in neuropathy, with greater loss of SGNFs in anhidrotic skin, possibly exceeding collateral reinnervation. Muscle Nerve 50: 528–534, 2014
The state of public affairs in Austria
Authors: Köppl Peter , Wippersberg Julia
Published: January 2014

Following almost five decades of federal coalition government between Social Democrats and People's Party alongside an interest mediation system that gave exclusivity to only a few institutions, from 2000 to 2006, Austria underwent a rapid transformation in the direction of a pluralistic free‐market interest mediation system. However, this short but intense interlude, which led to the development and establishment of professional public affairs in Austria, was stopped short by the return of the traditional Austrian interest mediation system. Following a series of so‐called lobbying scandals, in 2013, Austria introduced a mandatory lobbying and interest representation register at the federal level. Two years earlier, the industry formed its own trade association, the Austrian Public Affairs Association. A study commissioned by this association has for the first time shed light on the young public affairs industry, its actors, and the working environment. Copyright © 2014 John Wiley & Sons, Ltd.
Squamous cell carcinoma of larynx in an 8‐year‐old child: Successful management with chemo‐radiation
Authors: Kaur Jaspreet , Roy Soumyajit , Mallick Saumya Ranjan , Mathur Sandip , Sharma Atul , Bhasker Suman , Mohanti Bidhu Kalyan
Published: January 2014

Incidence of laryngeal squamous cell cancer (SCC) in childhood is rare, more so in children below 10 years of age. Due to the rarity of the disease and nonspecific symptoms diagnosis often gets delayed. Treatment is challenging and demands expert multi‐modality care. We describe the clinico‐pathologic findings and management of laryngeal cancer with chemo‐radiation in an 8‐year‐old male. After 18 months of completion of treatment the child is in complete remission clinically and radiologically. This report aims at increasing awareness of head and neck SCC in paediatric population and also underscores the importance of multi‐modality care in managing such cases. Pediatr Blood Cancer 2014; 61:1481–1483. © 2014 Wiley Periodicals, Inc.
Burden of diagnostic radiation exposure in children with sickle cell disease
Authors: Vetter Courtney L. , Buchanan George R. , Quinn Charles T.
Published: January 2014

Children with sickle cell disease (SCD) are repeatedly exposed to diagnostic radiation. We identified 938 children with SCD who had 9,246 radiographic tests. Mean number of tests/patient was 9.9 (95% CI: 8.9–10.9) over 8,817 patient‐years. Mean rate was 1.5 tests/year (95% CI: 1.3–1.6). On average, a child with SCD will have 26.7 (95% CI: 24.1–29.3) radiographic tests by 18 years of age, and 5% will have ≥100 tests. Six percent have ≥3 CT scans, which may be associated with an increased risk of cancer. Strong consideration should be given to limiting the exposure of children with SCD to radiation. Pediatr Blood Cancer 2014;61:1322–1324. © 2014 Wiley Periodicals, Inc.
Sulfo‐NHS‐SS‐biotin derivatization: A versatile tool for MALDI mass analysis of PTMs in lysine‐rich proteins
Authors: Markoutsa Stavroula , Bahr Ute , Papasotiriou Dimitrios G. , Häfner Ann‐Kathrin , Karas Michael , Sorg Bernd L.
Published: January 2014

The discovery of PTMs in proteins by MS requires nearly complete sequence coverage of the detected proteolytic peptides. Unfortunately, mass spectrometric analysis of the desired sequence fragments is often impeded due to low ionization efficiency and/or signal suppression in complex samples. When several lysine residues are in close proximity tryptic peptides may be too short for mass analysis. Moreover, modified peptides often appear in low stoichiometry and need to be enriched before analysis. We present here how the use of sulfo‐NHS‐SS‐biotin derivatization of lysine side chain can help to detect PTMs in lysine‐rich proteins. This label leads to a mass shift which can be adjusted by reduction of the SS bridge and alkylation with different reagents. Low intensity peptides can be enriched by use of streptavidin beads. Using this method, the functionally relevant protein kinase A phosphorylation site in 5‐lipoxygenase was detected for the first time by MS. Additionally, methylation and acetylation could be unambiguously determined in histones.
The utilization of fluorescence to identify the components of lipofuscin by imaging mass spectrometry
Authors: Ablonczy Zsolt , Smith Noah , Anderson David M. , Grey Angus C. , Spraggins Jeffrey , Koutalos Yiannis , Schey Kevin L. , Crouch Rosalie K.
Published: January 2014

Lipofuscin, an aging marker in the retinal pigment epithelium (RPE) associated with the development of age‐related macular degeneration, is primarily characterized by its fluorescence. The most abundant component of RPE lipofuscin is N‐retinylidene‐N‐retinylethanolamine (A2E) but its exact composition is not known due to the complexity of the RPE extract. In this study, we utilized MALDI imaging to find potential molecules responsible for lipofuscin fluorescence in RPE tissue from Abca4−/−, Sv129, and C57Bl6/J mice aged 2 and 6 months. To assert relationships, the individual images in the MALDI imaging datasets were correlated with lipofuscin fluorescence recorded from the same tissues following proper registration. Spatial correlation information, which is usually lost in bioanalytics, pinpointed a relatively small number of potential lipofuscin components. The comparison of four samples in each condition further limited the possibility of false positives and provided various new, age‐ and strain‐specific targets. Validating the usefulness of the fluorescence‐enhanced imaging strategy, many known adducts of A2E were identified in the short list of lipofuscin components. These results provided evidence that mass spectrometric imaging can be utilized as a tool to begin to identify the molecular substructure of clinically‐relevant diagnostic information.
Profiling of protein thiophosphorylation by Phos‐tag affinity electrophoresis: Evaluation of adenosine 5′‐O‐(3‐thiotriphosphate) as a phosphoryl donor in protein kinase reactions
Authors: Kinoshita Eiji , Kinoshita‐Kikuta Emiko , Shiba Akio , Edahiro Keisuke , Inoue Yuki , Yamamoto Kaneyoshi , Yoshida Myu , Koike Tohru
Published: January 2014

Adenosine 5′‐O‐(3‐thiotriphosphate) (ATPγS) has been widely used as a phosphoryl donor to trace protein kinase activities. However, the question remains whether particular kinases accept ATPγS as readily as they accept natural ATP. We investigated the characteristics of several kinase reactions in the presence of ATPγS by using Phos‐tag affinity electrophoresis. The Phos‐tag gel permitted quantitative analysis of thiophosphorylated proteins produced by kinase reactions in vitro and it identified differences in the efficiencies of utilization of ATPγS and ATP in these reactions. Using the method, we evaluated the utility of ATPγS as a phosphoryl donor in studies on bacterial two‐component systems. Histidine kinases accepted ATPγS as readily as they accepted ATP in autophosphorylation reactions. However, downstream phosphotransfer reactions with ATPγS were markedly slower than the corresponding reactions with ATP. In an analysis of the sluggish thiophosphate transfer, we found that detergent‐denatured thiophosphorylated histidine kinases gradually hydrolyzed at the P–N bond, even at neutral pH, during incubation for 24 h, whereas the native form of the thiophosphorylated enzymes were much more stable. Profiling of protein thiophosphorylation by using Phos‐tag affinity electrophoresis might provide new insights into the characteristics of various types of kinase reactions with ATPγS.