bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic Discovery of Abnormal Values in Large Textual Databases
Authors: Christen Peter , Gayler Ross W. , Tran Khoi-Nguyen , Fisher Jeffrey , Vatsalan Dinusha
Published: April 2016

Textual databases are ubiquitous in many application domains. Examples of textual data range from names and addresses of customers to social media posts and bibliographic records. With online services, individuals are increasingly required to enter their personal details for example when purchasing products online or registering for government services, while many social network and e-commerce sites allow users to post short comments. Many online sites leave open the possibility for people to enter unintended or malicious abnormal values, such as names with errors, bogus values, profane comments, or random character sequences. In other applications, such as online bibliographic databases or comparative online shopping sites, databases are increasingly populated in (semi-) automatic ways through Web crawls. This practice can result in low quality data being added automatically into a database. In this article, we develop three techniques to automatically discover abnormal (unexpected or unusual) values in large textual databases. Following recent work in categorical outlier detection, our assumption is that “normal” values are those that occur frequently in a database, while an individual abnormal value is rare. Our techniques are unsupervised and address the challenge of discovering abnormal values as an outlier detection problem. Our first technique is a basic but efficient q-gram set based technique, the second is based on a probabilistic language model, and the third employs morphological word features to train a one-class support vector machine classifier. Our aim is to investigate and develop techniques that are fast, efficient, and automatic. The output of our techniques can help in the development of rule-based data cleaning and information extraction systems, or be used as training data for further supervised data cleaning procedures. We evaluate our techniques on four large real-world datasets from different domains: two US voter registration databases containing personal details, the 2013 KDD Cup dataset of bibliographic records, and the SNAP Memetracker dataset of phrases from social networking sites. Our results show that our techniques can efficiently and automatically discover abnormal textual values, allowing an organization to conduct efficient data exploration, and improve the quality of their textual databases without the need of requiring explicit training data.
Challenges for Context-Driven Time Series Forecasting
Authors: Ulbricht Robert , Donker Hilko , Hartmann Claudio , Hahmann Martin , Lehner Wolfgang
Published: April 2016

Predicting time series is a crucial task for organizations, since decisions are often based on uncertain information. Many forecasting models are designed from a generic statistical point of view. However, each real-world application requires domain-specific adaptations to obtain high-quality results. All such specifics are summarized by the term of context. In contrast to current approaches, we want to integrate context as the primary driver in the forecasting process. We introduce context-driven time series forecasting focusing on two exemplary domains: renewable energy and sparse sales data. In view of this, we discuss the challenge of context integration in the individual process steps.
An Empirical Study on Randomized Optimal Area Polygonization of Planar Point Sets
Authors: Peethambaran Jiju , Parakkat Amal Dev , Muthuganapathy Ramanathan
Published: April 2016

While random polygon generation from a set of planar points has been widely investigated in the literature, very few works address the construction of a simple polygon with minimum area (MINAP) or maximum area (MAXAP) from a set of fixed planar points. Currently, no deterministic algorithms are available to compute MINAP/MAXAP, as the problems have been shown to be NP-complete. In this article, we present a greedy heuristic for computing the approximate MINAP of any given planar point set using the technique of randomized incremental construction. For a given point set of
n
points, the proposed algorithm takes
O
(
n
2
log 
n
) time and
O
(
n
) space. It is rather simplistic in nature, hence very easy for implementation and maintenance. We report on various experimental studies on the behavior of a randomized heuristic on different point set instances. Test data have been taken from the SPAETH cluster data base and TSPLIB library. Experimental results indicate that the proposed algorithm outperforms its counterparts for generating a tighter upper bound on the optimal minimum area polygon for large-sized point sets.
Eh?Placer
Authors: Darav Nima Karimpour , Kennings Andrew , Tabrizi Aysa Fakheri , Westwick David , Behjat Laleh
Published: April 2016

The placement problem has become more complex and challenging due to a wide variety of complicated constraints imposed by modern process technologies. Some of the most challenging constraints and objectives were highlighted during the most recent ACM/IEEE International Symposium on Physical Design (ISPD) contests. In this article, the framework of Eh?Placer and its developed algorithms are elaborated, with the main focus on modern technology constraints and runtime. The technology constraints considered as part of Eh?Placer are fence region, target density, and detailed routability constraints. We present a complete description on how these constraints are considered in different stages of Eh?Placer. The results obtained from the contests indicate that Eh?Placer is able to efficiently handle modern technology constraints and ranks highly among top academic placement tools.
Plasticity of sarcolemmal KATP channel surface expression: relevance during ischemia and ischemic preconditioning
Authors: Yang Hua-Qian , Foster Monique N. , Jana Kundan , Ho Joanne , Rindler Michael J. , Coetzee William A.
Published: April 2016

Myocardial ischemia remains the primary cause of morbidity and mortality in the United States. Ischemic preconditioning (IPC) is a powerful form of endogenous protection against myocardial infarction. We studied alterations in KATP channels surface density as a potential mechanism of the protection of IPC. Using cardiac-specific knockout of Kir6.2 subunits, we demonstrated an essential role for sarcolemmal KATP channels in the infarct-limiting effect of IPC in the mouse heart. With biochemical membrane fractionation, we demonstrated that sarcolemmal KATP channel subunits are distributed both to the sarcolemma and intracellular endosomal compartments. Global ischemia causes a loss of sarcolemmal KATP channel subunit distribution and internalization to endosomal compartments. Ischemia-induced internalization of KATP channels was prevented by CaMKII inhibition. KATP channel subcellular redistribution was also observed with immunohistochemistry. Ischemic preconditioning before the index ischemia reduced not only the infarct size but also prevented KATP channel internalization. Furthermore, not only did adenosine mimic IPC by preventing infarct size, but it also prevented ischemia-induced KATP channel internalization via a PKC-mediated pathway. We show that preventing endocytosis with dynasore reduced both KATP channel internalization and strongly mitigated infarct development. Our data demonstrate that plasticity of KATP channel surface expression must be considered as a potentially important mechanism of the protective effects of IPC and adenosine.
Targeted Dual-Modality Imaging in Renal Cell Carcinoma: An Ex Vivo Kidney Perfusion Study
Authors: Hekman Marlène C.H. , Boerman Otto C. , de Weijert Mirjam , Bos Desirée L. , Oosterwijk Egbert , Langenhuijsen Hans F. , Mulders Peter F.A. , Rijpkema Mark
Published: April 2016

Purpose: Antibodies labeled with both a near-infrared fluorescent dye and a radionuclide can be used for tumor-targeted intraoperative dual-modality imaging. Girentuximab is a chimeric monoclonal antibody against carbonic anhydrase IX (CAIX), an antigen expressed in 95% of clear cell renal cell carcinoma (ccRCC). This study aimed to assess the feasibility of targeted dual-modality imaging with 111In-girentuximab-IRDye800CW using ex vivo perfusion of human tumorous kidneys.

Experimental Design: Seven radical nephrectomy specimens from patients with ccRCC were perfused during 11 to 15 hours with dual-labeled girentuximab and subsequently rinsed during 2.5 to 4 hours with Ringer's Lactate solution. Then, dual-modality imaging was performed on a 5- to 10-mm-thick lamella of the kidney. Fluorescence imaging was performed with a clinical fluorescence camera set-up as applied during image-guided surgery. The distribution of Indium-111 in the slice of tumor tissue was visualized by autoradiography. In two perfusions, an additional dual-labeled control antibody was added to demonstrate specific accumulation of dual-labeled girentuximab in CAIX-expressing tumor tissue.

Results: Both radionuclide and fluorescence imaging clearly visualized uptake in tumor tissue and tumor-to-normal tissue borders, as confirmed (immuno)histochemically and by gamma counting. Maximum uptake of girentuximab in tumor tissue was 0.33% of the injected dose per gram (mean, 0.12 %ID/g; range, 0.01–0.33 %ID/g), whereas maximum uptake in the normal kidney tissue was 0.04 %ID/g (mean, 0.02 %ID/g; range, 0.00–0.04 %ID/g).

Conclusions: Dual-labeled girentuximab accumulated specifically in ccRCC tissue, indicating the feasibility of dual-modality imaging to detect ccRCC. A clinical study to evaluate intraoperative dual-modality imaging in patients with ccRCC has been initiated. Clin Cancer Res; 22(18); 4634–42. ©2016 AACR.
Comprehensive Molecular Characterization of Salivary Duct Carcinoma Reveals Actionable Targets and Similarity to Apocrine Breast Cancer
Authors: Dalin Martin G. , Desrichard Alexis , Katabi Nora , Makarov Vladimir , Walsh Logan A. , Lee Ken-Wing , Wang Qingguo , Armenia Joshua , West Lyndsay , Dogan Snjezana , Wang Lu , Ramaswami Deepa , Ho Alan L. , Ganly Ian , Solit David B. , Berger Michael F. , Schultz Nikolaus D. , Reis-Filho Jorge S. , Chan Timothy A. , Morris Luc G.T.
Published: April 2016

Purpose: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy, which is resistant to chemotherapy and has high mortality rates. We investigated the molecular landscape of SDC, focusing on genetic alterations and gene expression profiles.

Experimental Design: We performed whole-exome sequencing, RNA sequencing, and immunohistochemical analyses in 16 SDC tumors and examined selected alterations via targeted sequencing of 410 genes in a second cohort of 15 SDCs.

Results: SDCs harbored a higher mutational burden than many other salivary carcinomas (1.7 mutations/Mb). The most frequent genetic alterations were mutations in TP53 (55%), HRAS (23%), PIK3CA (23%), and amplification of ERBB2 (35%). Most (74%) tumors had alterations in either MAPK (BRAF/HRAS/NF1) genes or ERBB2. Potentially targetable alterations based on supportive clinical evidence were present in 61% of tumors. Androgen receptor (AR) was overexpressed in 75%; several potential resistance mechanisms to androgen deprivation therapy (ADT) were identified, including the AR-V7 splice variant (present in 50%, often at low ratios compared with full-length AR) and FOXA1 mutations (10%). Consensus clustering and pathway analyses in transcriptome data revealed striking similarities between SDC and molecular apocrine breast cancer.

Conclusions: This study illuminates the landscape of genetic alterations and gene expression programs in SDC, identifying numerous molecular targets and potential determinants of response to AR antagonism. This has relevance for emerging clinical studies of ADT and other targeted therapies in SDC. The similarities between SDC and apocrine breast cancer indicate that clinical data in breast cancer may generate useful hypotheses for SDC. Clin Cancer Res; 22(18); 4623–33. ©2016 AACR.
Surgical Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in White Matter Injury on Brain Magnetic Resonance Imaging
Authors: Shin Seung Han , Kim Ee-Kyung , Yoo Hani , Choi Young Hun , Kim Saeyun , Lee Byoung Kook , Jung Young Hwa , Kim Hyun-Young , Kim Han-Suk , Choi Jung-Hwan
Published: April 2016

Background: White matter injury (WMI) is the most common form of brain injury in preterm infants. It could be induced by a systemic inflammatory response in preterm infants. Objectives: We hypothesized that surgical necrotizing enterocolitis (surgNEC) results in more severe WMI than spontaneous intestinal perforation (SIP) on brain magnetic resonance imaging (MRI) at term-equivalent age (TEA). Methods: The medical records of 33 preterm infants born at less than 32 weeks of gestation who underwent surgery due to either NEC or SIP were reviewed retrospectively. White matter abnormality (WMA) on brain MRI was scored according to the diagnosis of surgNEC or SIP. Results: Nine patients were diagnosed with SIP and 24 with surgNEC. The median (range) gestational age of the SIP and surgNEC groups was 26+6 (23+3-27+6) and 25+5 weeks (23+3-31+2), respectively (p = 0.454). There were no differences in 1- and 5-min Apgar scores, mode of delivery, use of antenatal steroids, histologic chorioamnionitis, or incidence of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) between the two groups. Males were more prevalent in the surgNEC group (75.0 vs. 33.3%, p = 0.044), and the incidence of sepsis was higher in the surgNEC group than in the SIP group (75.0 vs. 33.3%, p = 0.044). Multivariate regression showed that the difference in WMA scores between the two groups remained significant (estimated difference = 2.418; 95% CI 0.107-4.729). Conclusion: In preterm infants at less than 32 weeks of gestation, those with surgNEC showed more severe WMI than infants with SIP on brain MRI at TEA.
Clinical Features of Food Allergy during the 1st Year of Life: The ADAPAR Birth Cohort Study
Authors: Doğruel Dilek , Bingöl Gülbin , Altıntaş Derya Ufuk , Yılmaz Mustafa , Güneşer Kendirli Seval
Published: April 2016

Background: Although food allergies (FAs) occur most commonly during the 1st year of life, there is limited information available regarding the epidemiology of FAs. In this study, we investigated the incidence of FA and the associated risk factors during the 1st year of life in southeast Turkey. Methods: This study is a prospective evaluation of 1,377 infants born at the Balcalı Hospital (Çukurova University) and includes four routine follow-up assessments until the age of 1 year. At birth, a physical examination was performed, cord blood samples were taken, and parents completed a baseline questionnaire. Follow-up visits were scheduled at 3, 6 and 12 months and included the infants' physical examination and a follow-up questionnaire. A skin prick test (SPT) was performed and food-specific IgE levels were measured at 6 and 12 months. Telephone interviews were conducted when the infants were 9 months of age, and the questionnaire was administered. The diagnosis of FA was based on food-specific IgE levels, positive SPT results, associated clinical findings and an oral food challenge (OFC) test. Results: Patient histories, physical examinations and laboratory results indicated a possible FA in 90 infants (6.5%) during the 1st year of life. All of them underwent OFC testing with the suspected foods, and FA was confirmed in 33 cases (2.4%). Cow's milk allergy was the major cause of FA. Skin reactions were major clinical findings in FA. A family history of atopy was identified as the major risk factor for FA. Conclusions: The prevalence and risk factors of FA in our region are consistent with those reported in the literature.
Dynamic Optical Coherence Tomography in Dermatology
Authors: Ulrich Martina , Themstrup Lotte , de Carvalho Nathalie , Manfredi Marco , Grana Costantino , Ciardo Silvana , Kästle Raphaela , Holmes Jon , Whitehead Richard , Jemec Gregor B.E. , Pellacani Giovanni , Welzel Julia
Published: April 2016

Optical coherence tomography (OCT) represents a non-invasive imaging technology, which may be applied to the diagnosis of non-melanoma skin cancer and which has recently been shown to improve the diagnostic accuracy of basal cell carcinoma. Technical developments of OCT continue to expand the applicability of OCT for different neoplastic and inflammatory skin diseases. Of these, dynamic OCT (D-OCT) based on speckle variance OCT is of special interest as it allows the in vivo evaluation of blood vessels and their distribution within specific lesions, providing additional functional information and consequently greater density of data. In an effort to assess the potential of D-OCT for future scientific and clinical studies, we have therefore reviewed the literature and preliminary unpublished data on the visualization of the microvasculature using D-OCT. Information on D-OCT in skin cancers including melanoma, as well as in a variety of other skin diseases, is presented in an atlas. Possible diagnostic features are suggested, although these require additional validation.
Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies
Authors: Barton Samantha K. , Tolcos Mary , Miller Suzanne L. , Roehr Charles Christoph , Schmölzer Georg M. , Moss Timothy J.M. , Hooper Stuart B. , Wallace Euan M. , Polglase Graeme R.
Published: April 2016

Mechanical ventilation is a risk factor for cerebral inflammation and brain injury in preterm neonates. The risk increases proportionally with the intensity of treatment. Recent studies have shown that cerebral inflammation and injury can be initiated in the delivery room. At present, initiation of intermittent positive pressure ventilation (IPPV) in the delivery room is one of the least controlled interventions a preterm infant will likely face. Varying pressures and volumes administered shortly after birth are sufficient to trigger pathways of ventilation-induced lung and brain injury. The pathways involved in ventilation-induced brain injury include a complex inflammatory cascade and haemodynamic instability, both of which have an impact on the brain. However, regardless of the strategy employed to deliver IPPV, any ventilation has the potential to have an impact on the immature brain. This is particularly important given that preterm infants are already at a high risk for brain injury simply due to immaturity. This highlights the importance of improving the initial respiratory support in the delivery room. We review the mechanisms of ventilation-induced brain injury and discuss the need for, and the most likely, current therapeutic agents to protect the preterm brain. These include therapies already employed clinically, such as maternal glucocorticoid therapy and allopurinol, as well as other agents, such as erythropoietin, human amnion epithelial cells and melatonin, already showing promise in preclinical studies. Their mechanisms of action are discussed, highlighting their potential for use immediately after birth.
Protein S100β in Late-Pregnancy Fetuses with Low Birth Weight and Abnormal Cerebroplacental Ratio
Authors: Morales-Roselló José , Khalil Asma , Alba-Redondo Amparo , Martinez-Triguero Luisa , Akhoundova Farida , Perales-Marín Alfredo , Thilaganathan Basky
Published: April 2016

Objective: To evaluate the umbilical cord venous S100β levels in late-pregnancy fetuses with abnormal growth and cerebral redistribution. Methods: The pulsatility index of the umbilical and middle cerebral arteries and the cerebroplacental ratio (CPR) were measured in 132 fetuses at ≥34 weeks, and the CPR was converted into multiples of the median (MoM). A blood sample from the umbilical vein was collected at birth, and the umbilical venous S100β levels were evaluated in small and non-small for gestational age (SGA) fetuses, with and without abnormal Doppler indices. The levels of S100β were correlated with birth weight (BW) centile, CPR MoM and cord venous pH. Results: While CPR MoM correlated with BW centile, S100β showed no correlation with any of the studied fetal parameters. In addition, no differences were observed in S100β level according to BW centile or Doppler parameters, neither was there any difference between SGA with low CPR MoM and non-SGA with normal CPR MoM. Conclusion: Late-pregnancy fetuses with abnormal growth or cerebral redistribution have normal cord blood levels of S100β at birth. In these fetuses, the potential consequences of chronic hypoxemia on the fetal brain might not be detectable using tissue necrosis markers.
Safety Concerns for Sclerotherapy of Telangiectases, Reticular and Varicose Veins
Authors: Yiannakopoulou Eugenia
Published: April 2016

Background: Sclerotherapy has been extensively used in the treatment of valvular insufficiency of superficial veins. Although sclerotherapy seems safe, reports of serious adverse events (AE) have been published. This paper aims to review AE of sclerosing agents. Methods: Electronical databases were searched for identifying articles on local, serious and long-term AE of sclerotherapy. Results: Hyperpigmentation and matting are the most often local AE of sclerotherapy. Other local AE include superficial thrombophlevitis, pyoderma gangrenosum, pain, ulcer formation, and hypertrichosis. Local AE can be serious, that is, it can include cutaneous necrosis, intra-arterial injection with subsequent acute ischemia that can lead to amputation, and necrotizing fasciitis. Most data on systemic AE of sclerotherapy are extracted from case series and case reports. Systemic AE include neurological complications, such as ischemic stroke, transient ischemic attack, visual disturbances and cardiac toxicity, that is, myocardial infarction, Takotsubo cardiomyopathy, chest tightness, pulmonary embolism, deep vein thrombosis, septicemia, anaphylaxis. It is difficult to estimate the frequency of serious systemic AE of sclerotherapy. Conclusion: Physicians practicing sclerotherapy should be aware of the possible local and systemic AE of sclerotherapy, inform patients accordingly and be prepared for the appropriate management of the rare but possibly lethal serious AE.
Medical Expulsive Therapy Following Shock Wave Lithotripsy in Ureteral Calculi: An Effective Approach for the Improvement of Health-Related Quality of Life
Authors: Eryildirim Bilal , Sahin Cahit , Tuncer Murat , Sabuncu Kubilay , Tarhan Fatih , Sarica Kemal
Published: April 2016

Objective: To evaluate the possible effects of medical expulsive therapy (MET) on the health-related quality of life (HRQOL) of patients undergoing shock wave lithotripsy (SWL) for ureteric stones. Methods: Eighty patients treated with SWL for ureteric stones were included in this study. Patients were divided into 2 groups; Group 1 received medical therapy only for colic pain and Group 2 received MET in addition to medical therapy. Patients requiring DJ stenting and auxiliary measures after SWL procedure were excluded. The remaining 54 patients were further evaluated (Group 1: n = 26, Group 2: n = 28) and followed up during the 4-week period for analgesic requirement, number of renal colic attacks, emergency department (ED) visits and the HRQOL scores by using EQ-5D index and EQ-5D visual analogue scale (VAS) values. Results: During the 4-week follow-up period, cases undergoing SWL only required significantly higher amount of analgesics. In addition to the lower number of renal colic attacks and ED visits, EQ-5D index and EQ-5D VAS values also demonstrated higher mean values in patients undergoing SWL + MET. Conclusion: In addition to the increased spontaneous stone passage rates, MET following SWL for ureteral calculi could increase the HRQOL scores by lowering the number of both renal colic attacks and ED visits along with decreased analgesic need.
Association Between Family History, a Genetic Risk Score, and Severity of Coronary Artery Disease in Patients With Premature Acute Coronary Syndromes
Authors: Hindieh Waseem , Pilote Louise , Cheema Asim , Al-Lawati Hatim , Labos Christopher , Dufresne Line , Engert James C. , Thanassoulis George
Published: April 2016

Objective—

A genetic risk score (GRS) for coronary artery disease has recently been shown to be independent of family history (FHx) in predicting future cardiovascular events. We sought to determine whether the presence of these risk factors, either individually or together, was associated with a higher burden of angiographic coronary artery disease.

Approach and Results—

We included 763 patients with premature acute coronary syndrome (median age, 50 [46–53] years; 30.8% women) with at least 1 major epicardial vessel stenosis enrolled in the Gender and Sex Determinants of Cardiovascular Disease From Bench to Beyond in Premature Acute Coronary Syndrome (GENESIS-PRAXY) study, a multicentre prospective cohort study of premature patients with acute coronary syndrome (aged ≤55 years). The prevalence of multivessel disease (ie, ≥2 vessels with >50% stenosis) in individuals with FHx was 49.7% as compared with 37.9% in those without FHx (
P
<0.01 for comparison). In adjusted models for age, sex, traditional risk factors, and GRS, FHx was associated with a higher prevalence of 3-vessel disease (odds ratio [OR], 1.42; 95% confidence interval, 0.91–2.21;
P
=0.12 for 2-vessel disease and OR, 2.26; 95% confidence interval, 1.29–3.95;
P
=0.005 for 3-vessel disease). Individuals with a high GRS were also more likely to have multivessel disease (OR, 1.41; 95% confidence interval, 1.01–1.99;
P
=0.047) after adjustment for traditional risk factors, including FHx. Individuals with both a FHx and a high GRS as compared with those with neither had the highest ORs for multivessel disease (adjusted OR, 2.14; 95% confidence interval, 1.24–3.69;
P
=0.0064).

Conclusions—

In patients with premature acute coronary syndrome, the presence of either a high GRS or FHx is associated with greater severity of coronary artery disease at angiography. Whether preventive strategies targeted to genetically predisposed individuals will reduce the burden of early acute coronary syndrome warrants further study.
Artery Tertiary Lymphoid Organs Control Multilayered Territorialized Atherosclerosis B-Cell Responses in Aged
ApoE

−/−

Mice
Authors: Srikakulapu Prasad , Hu Desheng , Yin Changjun , Mohanta Sarajo K. , Bontha Sai Vineela , Peng Li , Beer Michael , Weber Christian , McNamara Coleen A. , Grassia Gianluca , Maffia Pasquale , Manz Rudolf A. , Habenicht Andreas J.R.
Published: April 2016

Objective—

Explore aorta B-cell immunity in aged apolipoprotein E-deficient (
ApoE

−/−

) mice.

Approach and Results—

Transcript maps, fluorescence-activated cell sorting, immunofluorescence analyses, cell transfers, and Ig-ELISPOT (enzyme-linked immunospot) assays showed multilayered atherosclerosis B-cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B-cell–related transcriptomes were identified, and transcript atlases revealed highly territorialized B-cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B-cell genes, including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm although intima plaques preferentially expressed molecules involved in non–B effector responses toward B-cell–derived mediators, that is, Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B-cell recruitment. ATLO B-2 B cells included naive, transitional, follicular, germinal center, switched IgG1
+
, IgA
+
, and IgE
+
memory cells, plasmablasts, and long-lived plasma cells. ATLOs recruited large numbers of B-1 cells whose subtypes were skewed toward interleukin-10
+
B-1b cells versus interleukin-10
−
B-1a cells. ATLO B-1 cells and plasma cells constitutively produced IgM and IgG and a fraction of plasma cells expressed interleukin-10. Moreover,
ApoE

−/−

mice showed increased germinal center B cells in renal lymph nodes, IgM-producing plasma cells in the bone marrow, and higher IgM and anti–MDA-LDL (malondialdehyde-modified low-density lipoprotein) IgG serum titers.

Conclusions—

ATLOs orchestrate dichotomic, territorialized, and multilayered B-cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging.
A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research
Authors: Miano Joseph M. , Zhu Qiuyu Martin , Lowenstein Charles J.
Published: April 2016

Previous efforts to target the mouse genome for the addition, subtraction, or substitution of biologically informative sequences required complex vector design and a series of arduous steps only a handful of laboratories could master. The facile and inexpensive clustered regularly interspaced short palindromic repeats (CRISPR) method has now superseded traditional means of genome modification such that virtually any laboratory can quickly assemble reagents for developing new mouse models for cardiovascular research. Here, we briefly review the history of CRISPR in prokaryotes, highlighting major discoveries leading to its formulation for genome modification in the animal kingdom. Core components of CRISPR technology are reviewed and updated. Practical pointers for 2-component and 3-component CRISPR editing are summarized with many applications in mice including frameshift mutations, deletion of enhancers and noncoding genes, nucleotide substitution of protein-coding and gene regulatory sequences, incorporation of
loxP
sites for conditional gene inactivation, and epitope tag integration. Genotyping strategies are presented and topics of genetic mosaicism and inadvertent targeting discussed. Finally, clinical applications and ethical considerations are addressed as the biomedical community eagerly embraces this astonishing innovation in genome editing to tackle previously intractable questions.
P-Selectin Expressed by a Human
SELP
Transgene Is Atherogenic in Apolipoprotein E–Deficient Mice
Authors: Zhang Nan , Liu Zhenghui , Yao Longbiao , Mehta-D’souza Padmaja , McEver Rodger P.
Published: April 2016

Objective—

During inflammation, P-selectin expressed on activated endothelial cells and platelets mediates rolling adhesion of leukocytes. Atherosclerosis-prone mice crossed with P-selectin–deficient (
Selp

−/−

) mice develop smaller lesions. Cytokines, such as tumor necrosis factor-α, increase
Selp
transcripts and augment atherosclerosis in mice. However, they decrease
SELP
transcripts in humans, challenging assumptions that human P-selectin is atherogenic. We used mice expressing a human
SELP
transgene to examine the atherogenic role of P-selectin.

Approach and Results—

We crossed apolipoprotein E–deficient (
Apoe

−/−

) mice with
Selp

−/−

mice or transgenic mice expressing the entire human
SELP
gene (
TgSELP

+/−

). Aortas developed larger, macrophage-rich atheromas in
Apoe

−/−

Selp

−/−

TgSELP

+/−

mice than in
Apoe

−/−

Selp

−/−

mice after 8 or 16 weeks on a Western diet. Confocal microscopy of
Apoe

−/−

Selp

−/−

TgSELP

+/−

aortas revealed staining for human P-selectin in endothelial cells overlying atheromas but not in lesional macrophages. We also observed staining for human P-selectin in aortic endothelial cells of 3- to 4-week-old
Apoe

−/−

Selp

−/−

TgSELP

+/−

weanlings before atheromas developed. Furthermore, human
SELP
transcripts were ≈3-fold higher in aortas of
Apoe

−/−

Selp

+/−

TgSELP

+/−

weanlings than in
Selp

+/−

TgSELP

+/−

weanlings, whereas murine
Selp
and
Sele
transcripts were equivalent in weanlings of both genotypes. Human
SELP
transcripts in aortas of
Apoe

−/−

Selp

+/−

TgSELP

+/−

mice remained nearly constant during 16 weeks on a Western diet, whereas murine
Selp
and
Sele
transcripts progressively increased. Bone marrow transplantation in
Apoe

−/−

Selp

−/−

and
Apoe

−/−

Selp

−/−

TgSELP

+/−

mice demonstrated that both platelets and endothelial cells must express human P-selectin to promote atherogenesis.

Conclusions—

P-selectin expressed by human
SELP
is atherogenic in
Apoe

−/−

mice, suggesting that P-selectin contributes to atherogenesis in humans.
Cardiovascular Risk Factors and Ischemic Heart Disease
Authors: Elosua Roberto , Lluís-Ganella Carla , Subirana Isaac , Havulinna Aki , Läll Kristi , Lucas Gavin , Sayols-Baixeras Sergi , Pietilä Arto , Alver Maris , Cabrera de León Antonio , Sentí Mariano , Siscovick David , Mellander Olle , Fischer Krista , Salomaa Veikko , Marrugat Jaume
Published: April 2016

Background—

Cardiovascular risk factors tend to aggregate. The biological and predictive value of this aggregation is questioned and genetics could shed light on this debate. Our aims were to reappraise the impact of risk factor confluence on ischemic heart disease (IHD) risk by testing whether genetic risk scores (GRSs) associated with these factors interact on an additive or multiplicative scale, and to determine whether these interactions provide additional value for predicting IHD risk.

Methods and Results—

We selected genetic variants associated with blood pressure, body mass index, waist circumference, triglycerides, type-2 diabetes mellitus, high-density lipoprotein and low-density lipoprotein cholesterol, and IHD to create GRSs for each factor. We tested and meta-analyzed the impact of additive (synergy index) and multiplicative (β
interaction
) interactions between each GRS pair in 1 case–control (n=6042) and 4 cohort studies (n=17 794) and evaluated the predictive value of these interactions. We observed 2 multiplicative interactions: GRS
LDL
·GRS
Triglycerides
(β
interaction
=–0.096; SE=0.028) and nonpleiotropic GRS
IHD
·GRS
LDL
(β
interaction
=0.091; SE=0.028). Inclusion of these interaction terms did not improve predictive capacity.

Conclusions—

The confluence of low-density lipoprotein cholesterol and triglycerides genetic risk load has an additive effect on IHD risk. The interaction between low-density lipoprotein cholesterol and IHD genetic load is more than multiplicative, supporting the hazardous impact on atherosclerosis progression of the combination of inflammation and increased lipid levels. The capacity of risk factor confluence to improve IHD risk prediction is questionable. Further studies in larger samples are warranted to confirm and expand our results.
Decade Long Trends (2001–2011) in Duration of Pre‐Hospital Delay Among Elderly Patients Hospitalized for an Acute Myocardial Infarction
Authors: Makam Raghavendra P. , Erskine Nathaniel , Yarzebski Jorge , Lessard Darleen , Lau Jason , Allison Jeroan , Gore Joel M. , Gurwitz Jerry , McManus David D. , Goldberg Robert J.
Published: April 2016

Background

Early intervention with medical and/or coronary revascularization treatment approaches remains the cornerstone of the management of patients hospitalized with acute myocardial infarction (
AMI
). However, several patient groups, especially the elderly, are known to delay seeking prompt medical care after onset of
AMI
‐associated symptoms. Current trends, and factors associated with prolonged prehospital delay among elderly patients hospitalized with
AMI
, are incompletely understood.

Methods and Results

Data from a population‐based study of patients hospitalized at all 11 medical centers in central Massachusetts with a confirmed
AMI
on a biennial basis between 2001 and 2011 were analyzed. Information about duration of prehospital delay after onset of acute coronary symptoms was abstracted from hospital medical records. In patients 65 years and older, the overall median duration of prehospital delay was 2.0 hours, with corresponding median delays of 2.0, 2.1, and 2.0 hours in those aged 65 to 74 years, 75 to 84 years, and in patients 85 years and older, respectively. There were no significant changes over time in median delay times in each of the age strata examined in both crude and multivariable adjusted analyses. A limited number of patient characteristics were associated with prolonged delay in this patient population.

Conclusions

The results of this community‐wide study demonstrate that delay in seeking prompt medical care continues to be a significant problem among elderly patients hospitalized with
AMI
. The lack of improvement in the timeliness of patients’ care‐seeking behavior during the years under study remains of considerable clinical and public health concern.
Leukocyte Count and Intracerebral Hemorrhage Expansion
Authors: Morotti Andrea , Phuah Chia-Ling , Anderson Christopher D. , Jessel Michael J. , Schwab Kristin , Ayres Alison M. , Pezzini Alessandro , Padovani Alessandro , Gurol M. Edip , Viswanathan Anand , Greenberg Steven M. , Goldstein Joshua N. , Rosand Jonathan
Published: April 2016

Background and Purpose—

Acute leukocytosis is a well-established response to intracerebral hemorrhage (ICH). Leukocytes, because of their interaction with platelets and coagulation factors, may in turn play a role in hemostasis. We investigated whether admission leukocytosis was associated with reduced bleeding after acute ICH.

Methods—

Consecutive patients with primary ICH were prospectively collected from 1994 to 2015 and retrospectively analyzed. We included subjects with a follow-up computed tomographic scan available and automated complete white blood cell count performed within 48 hours from onset. Baseline and follow-up hematoma volumes were calculated with semiautomated software, and hematoma expansion was defined as volume increase >30% or 6 mL. The association between white blood cell count and ICH expansion was investigated with multivariate logistic regression.

Results—

A total of 1302 subjects met eligibility criteria (median age, 75 years; 55.8% men), of whom 207 (15.9%) experienced hematoma expansion. Higher leukocyte count on admission was associated with reduced risk of hematoma expansion (odds ratio for 1000 cells increase, 0.91; 95% confidence interval, 0.86–0.96;
P
=0.001). The risk of hematoma expansion was inversely associated with neutrophil count (odds ratio, 0.90; 95% confidence interval, 0.85–0.96;
P
=0.001) and directly associated with monocyte count (odds ratio, 2.71; 95% confidence interval, 1.08–6.83;
P
=0.034). There was no association between lymphocyte count and ICH expansion (odds ratio, 0.96; 95% confidence interval, 0.79–1.17;
P
=0.718).

Conclusions—

Higher admission white blood cell count is associated with lower risk of hematoma expansion. This highlights a potential role of the inflammatory response in modulating the coagulation cascade after acute ICH.
A new species of Catocala Schrank, 1802 (Lepidoptera: Noctuidae) from Primorsky Krai, Russia
Authors: KONS JR. HUGO L. , BORTH ROBERT J. , SALDAITIS AIDAS
Published: April 2016

Here we describe Catocala didenko sp. n. as new for the noctuid genus Catocala Shrank, differing from Catocala duplicata Butler, 1885 and Catocala gansan Ishizuka & Wang, 2013 on wing pattern, male genitalia, and COI 5’ mitochondrial DNA. These three species, along with Catocala dissimilis Bremer, 1861, comprise a small and distinctive species group within the genus. Exemplary uncommon morphological characters for this group include: extensive area of ventral side of claspers unsclerotized (Fig. 17); claspers with a subapical ventral bulging projection (Fig. 17); sclerotized apex of claspers greatly expanded laterally (Fig. 17); diaphragma posterior to anellus lightly pigmented (Fig. 22); distinctive anellus shape (Fig. 22); uncus setae longest and densest at base (Fig. 21); and approximately 17-20 coils on the receptacle duct (Fig. 56).
JODI J. L. ROWLEY, DAO T. A. TRAN, DUONG T. T. LE, VINH Q. DAU, PEDRO L. V. PELOSO, TRUONG Q. NGUYEN, HUY D. HOANG, TAO T. NGUYEN & THOMAS ZIEGLER (2016) Five new, microendemic Asian Leaf-litter Frogs (Leptolalax) from the southern Annamite mountains, Vietnam. Zootaxa, 4085(1): 063–102.
Authors: ROWLEY JODI J. L. , TRAN DAO T. A. , LE DUONG T. T. , DAU VINH Q. , PELOSO PEDRO L. V. , NGUYEN TRUONG Q. , HOANG HUY D. , NGUYEN TAO T. , ZIEGLER THOMAS
Published: April 2016

N/A
Resource Allocation for Lagrangian Tracking
Authors: Jones Benjamin T. , Solow Andrew , Ji Rubao
Published: April 2016

Accurate estimation of the transport probabilities among regions in the ocean provides valuable information for understanding plankton transport, the spread of pollutants, and the movement of water masses. Individual-based particle-tracking models simulate a large ensemble of Lagrangian particles and are a common method to estimate these transport probabilities. Simulating a large ensemble of Lagrangian particles is computationally expensive, and appropriately allocating resources can reduce the cost of this method. Two universal questions in the design of studies that use Lagrangian particle tracking are how many particles to release and how to distribute particle releases. A method is presented for tailoring the number and the release location of particles to most effectively achieve the objectives of a study. The method detailed here is a sequential analysis procedure that seeks to minimize the number of particles that are required to satisfy a predefined metric of result quality. The study assesses the result quality as the precision of the estimates for the elements of a transport matrix and also describes how the method may be extended for use with other metrics. Applying this methodology to both a theoretical system and a particle transport model of the Gulf of Maine results in more precise estimates of the transport probabilities with fewer particles than from uniformly or randomly distributing particle releases. The application of this method can help reduce the cost of and increase the robustness of results from studies that use Lagrangian particles.
Christian and Muslim Immigrant Women in the Canadian Maritimes
Authors: Holtmann Catherine
Published: April 2016

This article details the strengths and vulnerabilities that Christian and Muslim immigrant women bring to situations of domestic violence in the Canadian Maritimes. An intersectional theoretical framework grounds the analysis of qualitative data collected from 89 Christian and Muslim women from 27 countries of origin who arrived in the region ten years prior to the field work. Their strengths include high levels of education, experiences of overcoming adversity, the ability to act strategically, and the use of social networks, while factors such as increased dependence on husbands, transnational family situations, responsibilities for family unity, and a lack of knowledge about local services are vulnerabilities. The findings show that Orthodox and Catholic Christians, Muslim women with young children, immigrant women employed full-time immediately upon arrival, and wives whose immigration is sponsored by their husbands lack access to important social support networks.
Urban studies after the age of the city
Authors: Rickards Lauren , Gleeson Brendan , Boyle Mark , O’Callaghan Cian
Published: April 2016

For some time now, the field of urban studies has been attempting to figure the urban whilst cognisant of the fact that the city exists as a highly problematic category of analysis. In this virtual special issue, we draw together some examples of what we call urban concepts under stress; concepts which appear to be reaching the limits of their capacity to render knowable a world characterised by the death of the city and the ascent of multi-scalar de-territorialisations and re-territorialisations. We organise the papers selected for inclusion into three bundles dealing respectively with complex urban systems, the hinterland problematic and governing cities in the age of flows. The phenomenon of urban concepts under stress stems from the existence of a gap between existing cartographies, visualisations and lexicons of the urban and 21st century spatial conditions and territorialities. Given that this disarticulation will surely increase as this century unfolds, a pressing question presents itself: what is to be done with the field of urban studies after the age of the city? In this introduction, we argue that there exist at least six ways of responding to the present conceptual difficulties, each implying a different future for urban studies. We place under particular scrutiny voices which argue that nothing less than a scholarly tabula rasa will suffice. Our conclusion is that the phenomenon of concepts under stress provides an opportunity to think afresh about what to do with the field of urban studies and that it is premature to foreclose discussion about possible futures at this point.
Investigating the Effect of Socio-Cognitive Salience and Speaker-Based Factors in Morpho-Syntactic Life-Span Change
Authors: Buchstaller Isabelle
Published: April 2016

This article explores changes across the life-span of the individual speaker. Three morpho-syntactic variables that operate at different levels of socio-cognitive salience—quotation, stative possession, and future temporal reference—are traced across longitudinal trend and panel data. The analysis of a panel corpus that spans forty-two years reveals that linguistic malleability is contingent on the variables’ embedding in speakers’ cognitive-evaluative structures but also on a range of speaker-based factors, such as the speakers’ socio-economic trajectory, personality profile, as well as their type and intensity of contact with children and younger speakers. The study thus supports research that has shown that the adaptive behavior across the life-span results in complex outcomes that cannot be characterized by wholesale convergence or divergence.
Interrater Agreement on the Visual Analysis of Individual Tiers and Functional Relations in Multiple Baseline Designs
Authors: Wolfe Katie , Seaman Michael A. , Drasgow Erik
Published: April 2016

Previous research on visual analysis has reported low levels of interrater agreement. However, many of these studies have methodological limitations (e.g., use of AB designs, undefined judgment task) that may have negatively influenced agreement. Our primary purpose was to evaluate whether agreement would be higher than previously reported if we addressed these weaknesses. Our secondary purposes were to investigate agreement at the tier level (i.e., the AB comparison) and at the functional relation level in multiple baseline designs and to examine the relationship between raters’ decisions at each of these levels. We asked experts ( N = 52) to make judgments about changes in the dependent variable in individual tiers and about the presence of an overall functional relation in 31 multiple baseline graphs. Our results indicate that interrater agreement was just at or just below minimally adequate levels for both types of decisions and that agreement at the individual tier level often resulted in agreement about the overall functional relation. We report additional findings and discuss implications for practice and future research.
Capitalism and the media: moral economy, well-being and capabilities
Authors: Hesmondhalgh David
Published: April 2016

This article aims to contribute to the renewal of consideration of media and culture under capitalism, by seeking solid normative foundations for critique via various compatible elements: moral economy, well-being understood as flourishing and Sen and Nussbaum’s capabilities approach. Insufficient attention has been paid to normative and conceptual issues concerning capitalism, media and culture. Moral economy approaches might help fill this gap by valuably providing a richly critical ethics-based approach, drawing on political economy, cultural studies and social theory. Two further concepts, compatible with moral economy, can reinvigorate and renew critique of capitalism, media and culture. The first is a particular (Aristotelian) conception of well-being, understood as flourishing. This is outlined, and its potential contribution to critique of media and culture under capitalism is explicated. The second concept is capabilities, which can provide a basis for dealing with different understandings of flourishing. The article outlines the capabilities approach, analyses rare applications of it to media and culture, and explains how these applications might be built upon, by developing Nussbaum’s work in a way that could ground critique in an understanding of the potential value of media and culture in contributing to people’s flourishing.