bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Rating Agencies Benefit from Providing Higher Ratings? Evidence from the Consequences of Municipal Bond Ratings Recalibration
Authors: BEATTY ANNE , GILLETTE JACQUELYN , PETACCHI REINING , WEBER JOSEPH
Published: March 2019

We ask whether credit rating agencies receive higher fees and gain greater market share when they provide more favorable ratings. To investigate this question, we use the 2010 rating scale recalibration by Moody's and Fitch, which increased ratings absent any underlying change in issuer credit quality. Consistent with prior research, we find that the recalibration allowed the clients of Moody's and Fitch to receive better ratings and lower yields. We add to this evidence by showing that the recalibration also led to larger fees and to increases in the market shares of Moody's and Fitch. These results are consistent with critics’ concerns about the effects of the issuer‐pay model on the credit ratings market.
Assessing dangerousness in policing
Authors: White Michael D. , Dario Lisa M. , Shjarback John A.
Published: March 2019

Research Summary

A robust body of research findings has established that policing is a dangerous profession. Few scholars, however, have investigated the full picture of the hazards in policing, which includes deaths occurring in both felonious and nonfelonious circumstances. In this study, we examine nearly 50 years of all police officer line‐of‐duty deaths (1970–2016) using data from the Officer Down Memorial Page. We focus on long‐term trends in felonious and nonfelonious deaths annually, as well as on trends in incident‐level characteristics. We also employ interrupted time‐series analysis (ARIMA) to test the “war on cops” thesis post–Ferguson.

Policy Implications

The number of line‐of‐duty deaths has declined dramatically over the last five decades. Policing is a much safer profession now than it was 50 years ago. Despite a 75% drop in deaths, however, there has been remarkable stability in geographic‐, temporal‐, and incident‐level characteristics. Also, several notable changes over time reflect favorably on improved safety in policing, such as declines in deaths resulting from aircraft crashes and accidental gunfire. Other trends are troubling, though, such as the stability in deaths during auto pursuits and a two‐fold increase in deaths from vehicular assaults. Currently, the “war on cops” thesis is not supported by any evidence, and we apply the 50‐year lens in this study to provide important context for understanding recent trends in officer deaths.
Relation Between Oppositional/Conduct Behaviors and Executive Function Among Youth with Histories of Heavy Prenatal Alcohol Exposure
Authors: Doyle Lauren R. , Glass Leila , Wozniak Jeffrey R. , Kable Julie A. , Riley Edward P. , Coles Claire D. , Sowell Elizabeth R. , Jones Kenneth Lyons , Mattson Sarah N. ,   the CIFASD
Published: March 2019

Background

Youth with heavy prenatal alcohol exposure have high rates of behavioral concerns and psychopathology, including increased oppositional and conduct behaviors. The relation between those concerns and executive function (EF) deficits is unknown. We investigated the association of oppositional and conduct behavior and EF in adolescents to inform targeted intervention.

Methods

Subjects (N = 267) ages 10 to 17 years comprised 3 groups: alcohol‐exposed with oppositional/conduct behaviors (AE+), alcohol‐exposed without oppositional/conduct behaviors (AE−), and controls (CON). Group differences on direct neuropsychological (Delis‐Kaplan Executive Function System [D‐KEFS]) and indirect parent‐report (Behavior Rating Inventory of Executive Function [BRIEF]) EF measures were tested with multivariate analysis of covariances, followed by univariate analysis of variances and pairwise comparisons. The contribution of attention‐deficit/hyperactivity disorder (ADHD) within the AE groups was assessed in secondary analyses.

Results

On the D‐KEFS, there was an omnibus main effect of group, with significant main effects on 3 of 6 variables (CON>AE+, AE−). Within the AE groups, ADHD did not alter the results. On the BRIEF, there was an omnibus significant main effect of group, with significant main effects on all scales (CON<AE−<AE+). Within the AE groups, the AE+ group had higher BRIEF scores (i.e., more difficulty) than the AE− group on 4 of 8 subscales when accounting for presence of ADHD.

Conclusions

EF deficits in youth with histories of prenatal alcohol exposure were confirmed using direct and indirect measures. Oppositional/conduct behaviors related to EF deficits on indirect but not direct EF measures. Greater understanding of the contribution of concurrent psychopathology to long‐term outcomes for alcohol‐exposed youth requires further investigation.
Aberrant insular cortex connectivity in abstinent alcohol‐dependent rats is reversed by dopamine D3 receptor blockade
Authors: Scuppa Giulia , Tambalo Stefano , Pfarr Simone , Sommer Wolfgang H. , Bifone Angelo
Published: March 2019

A few studies have reported aberrant functional connectivity in alcoholic patients, but the specific neural circuits involved remain unknown. Moreover, it is unclear whether these alterations can be reversed upon treatment. Here, we used functional MRI to study resting state connectivity in rats following chronic intermittent exposure to ethanol. Further, we evaluated the effects of SB‐277011‐a, a selective dopamine D3 receptor antagonist, known to decrease ethanol consumption. Alcohol‐dependent and control rats (N = 13/14 per group), 3 weeks into abstinence, were administered SB‐277011‐a or vehicle before fMRI sessions. Resting state connectivity networks were extracted by independent component analysis. A dual‐regression analysis was performed using independent component maps as spatial regressors, and the effects of alcohol history and treatment on connectivity were assessed. A history of alcohol dependence caused widespread reduction of the internal coherence of components. Weaker correlation was also found between the insula cortex (IC) and cingulate cortices, key constituents of the salience network. Similarly, reduced connectivity was observed between a component comprising the anterior insular cortex, together with the caudate putamen (CPu‐AntIns), and the posterior part of the IC. On the other hand, postdependent rats showed strengthened connectivity between salience and reward networks. In particular, higher connectivity was observed between insula and nucleus accumbens, between the ventral tegmental area and the cingulate cortex and between the VTA and CPu‐AntIns. Interestingly, aberrant connectivity in postdependent rats was partially restored by acute administration of SB‐277011‐a, which, conversely, had no significant effects in naïve rats.
Spatial dynamic analysis of productivity growth of agri‐food companies
Authors: Martínez‐Victoria MCarmen , Maté‐Sánchez‐Val Mariluz , Lansink Alfons Oude
Published: March 2019

This study analyzes the spatial dynamics in productivity growth and its components for a sample of agri‐food companies in Murcia (Spain) over the period 2005–2014. We find that productivity growth of a company is related to productivity growth of neighboring companies, in both the short and long term. The marginal effects of the different factors on productivity growth are stronger in the short run rather than in the long run. Land characteristics and economic territorial conditions have the largest marginal effect on productivity growth and its components. This study contributes to the existing literature by including spatial interactions in the analysis of productivity growth.
NEW DIRECTIONS IN THE AETIOLOGY OF ULCERATIVE COLITIS
Authors: ROEDIGER W. E. W.
Published: March 2019

The causative factors of ulcerative colitis remain unknown. Cellular biochemistry has revealed altered oxidative metabolism, membrane function and synthesis of mucus in colonic epithelial cells in the early stages of ulcerative colitis. Immune studies have highlighted more precise changes in neutrophil and macrophage function in cells of the lamina propria while microbiological evidence has shown a dysbiosis of colonic bacteria related to entero‐adhesion, release of bacterial peptides and formation of secondary bacterial metabolites (mercapto fatty acids). A precise sequence of pathological events still needs to be established to account for an acute attack of ulcerative colitis.
GASTROSCHISIS AND EXOMPHALOS: RECENT TRENDS AND FACTORS INFLUENCING SURVIVAL
Authors: KOHN M. R. , SHI E. C. P.
Published: March 2019

The present study examined the treatment and survival of patients with gastroschisis and exomphalos in the 5‐year period January 1982–December 1987, at the Prince of Wales Children's Hospital. There were 15 cases of gastroschisis and 17 cases of exomphalos. The influences of temperature on arrival, birthweight, method of repair and associated anomalies on survival were examined. More patients presenting with gastroschisis survived than those with exomphalos (14 of 15 compared with 10 of 17, respectively). Of all the factors examined, the presence and nature of associated anomalies is the most important in determining survival.
“I've never told anyone this before”: Co‐constructing intimacy in sex and sexualities research
Authors: Miles Sam
Published: March 2019

This paper explores the co‐construction of a temporary yet intimate relationship between researcher and participant when discussing participants’ personal lives in fieldwork interviews. Through the case study of a project exploring how men who have sex with men use geolocative mobile phone apps for social and sexual encounter, I explore how the researcher and participant can experience moments of striking intimacy while maintaining personal and professional boundaries. The paper contributes to sex and sexualities research by arguing that intimacy can be cohered spatially and in limited timeframes, contrary to critical approaches suggesting that longer term and more intimately involved ethnographies are necessary for rich empirical results. In an environment of restrictive institutional ethical norms, this paper provides a methodological road‐map for scaffolding an environment for intimate relating that maximises participant engagement while managing (inter)personal boundaries.
“Nobody Ever Asks Me:” A Reproductive Justice Approach to Rural Health Disparities
Authors: Smith Ellie , Sundstrom Beth , DeMaria Andrea L.
Published: March 2019

Rural women within the southern United States face complex challenges when attempting to access reproductive health care. A reproductive justice framework provides an intersectional approach to understanding the experiences of women from varying backgrounds. Researchers conducted 52 in‐depth interviews with women aged 18–44 years in rural South Carolina to understand perceived reproductive health care barriers through a reproductive justice framework. Interviews were analyzed using a constant‐comparative method with qualitative data analysis software HyperRESEARCH 3.7.2. Reproductive justice served as the conceptual lens. Participants noted barriers to reproductive health care including cost, poor quality of care, and long wait times. Participants described confidentiality concerns and lack of facilities. Insufficient access to health care for women in conjunction with racial and cultural norms revealed intersectionality between gender and race. Participants reported limited autonomy over health decisions due to generational habits of not seeking care and predetermined attitudes toward health, influencing social capital and access to care. Findings suggest the need for grassroots organizing to shift the focus from reproductive rights to reproductive justice, facilitating autonomous health decisions and supportive environments to exercise decision making. Robust understandings of women's lived experiences offer insights to addressing health barriers in rural communities.
Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: A network meta‐analysis
Authors: Fachi Mariana M. , Tonin Fernanda S. , Leonart Leticia P. , Rotta Inajara , Fernandez‐Llimos Fernando , Pontarolo Roberto
Published: March 2019

Aims

Despite their overall favourable safety profile, tyrosine kinase inhibitors (TKIs) are related to severe adverse events including haematological toxicities such as anaemia, leucopenia, neutropenia and thrombocytopenia. We designed a systematic review and network meta‐analysis of randomised controlled trials to compare safety among TKIs (bosutinib, dasatinib, imatinib, nilotinib, ponatinib and radotinib) used by patients diagnosed with chronic myeloid leukaemia.

Methods

We obtained data from the PubMed, Scopus, Web of Science, and SciELO databases. The Bayesian approach was used for direct and indirect comparisons, and the treatments were ranked by the surface under the cumulative ranking curve (SUCRA).

Results

Seventeen studies were included in the network meta‐analysis. Our data show that dasatinib was generally considered worse than the other TKIs, with SUCRA values ​​for 140 mg dasatinib of 90.3% for anaemia, 87.4% for leucopenia, 90.6% for neutropenia and 97.2% for thrombocytopenia. In addition, nilotinib was shown to be safer, with SUCRA values ​​for 600 and 800 mg doses of 21.9 and 35.8% for anaemia, 23.8 and 14.6% for leucopenia, 33.0 and 17.7% for neutropenia, and 28.7 and 32.6% for thrombocytopenia, respectively.

Conclusion

Dasatinib appeared as the least safe drug for chronic myeloid leukaemia, probably because it binds to multiple key kinase targets, being more prone to cause serious haematological adverse events. Nilotinib demonstrated a safer profile, mostly due to its selective binding capacity.
A Toll‐like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease
Authors: Tozatto‐Maio Karina , Girot Robert , Ly Indou D. , Rocha Vanderson , Silva Pinto Ana C. , Diagne Ibrahima , Benzerara Yahia , Dinardo Carla L. , Kashima Simone , Leston‐Araujo Itauá , Kenzey Chantal , Fonseca Guilherme H. H. , Rodrigues Evandra S. , Volt Fernanda , Jarduli Luciana R. , Ruggeri Annalisa , Mariaselvam Christina M. , Gualandro Sandra F. M. , Elayoubi Hanadi , Cunha Renato , Cappelli Barbara , Malmegrim Kelen C. R. , Simões Belinda P. , Gluckman Eliane , Tamouza Ryad
Published: March 2019

Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll‐like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients withSCD. A cohort followed in centres in Brazil, France and Senegal (n = 430) was divided in two groups: patients who presented at least one episode of bacterial infection (n = 235) and patients who never had bacterial infections (n = 195). There were no differences in gender or age distribution among the groups. The frequency of theTLR2rs4696480TAgenotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR] = 0·50, 95% confidence interval [CI] 0·34–0·75,P < 0·001), and theTTgenotype was significantly higher in the infected group (15% vs. 5%,OR = 3·18, 95%CI1·53–6·61,P < 0·001). Previous reports demonstrated higher secretion of inflammatory factors in cells fromAAindividuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480TAgenotype might stand between deleterious effects of over inflammatory response (AAgenotype) and inefficient responses (TTgenotype) to infectious agents inSCDsettings.
Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy
Authors: Zamboni Stefania , Foerster Beat , Abufaraj Mohammad , Seisen Thomas , Roupret Morgan , Colin Pierre , De la Taille Alexandre , Di Bona Carlo , Peyronnet Benoit , Bensalah Karim , Herout Roman , Wirth Manfred Peter , Novotny Vladimir , Soria Francesco , Chlosta Piotr , Antonelli Alessandro , Simeone Claudio , Baumeister Philipp , Mattei Agostino , Montorsi Francesco , Simone Giuseppe , Gallucci Michele , Matsumoto Kazumasa , Karakiewicz Pierre I. , Briganti Alberto , Xylinas Evanguelos , Shariat Shahrokh F. , Moschini Marco ,   Upper Tract Urothelial Carcinoma Collaboration Group,   the European Association of Urology ‐ Young Academic Urologists (EAU‐YAU), Urothelial carcinoma working group
Published: March 2019

Objective

To evaluate the incidence and survival outcomes of histological variants of upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).

Materials and Methods

We retrospectively analysed data from 1610 patients treated with RNU for clinically non‐metastatic UTUC between 1990 and 2016 in several centres participating in the UTUC Collaboration. Histological variants were classified as micropapillary, squamous, sarcomatoid and other, including other rare variants (<10 cases for each). Multivariable competing risk analyses were conducted to assess the effect of variant histology on overall recurrence and cancer‐specific mortality (CSM).

Results

Overall, 1460 patients (91%) had pure urothelial carcinoma (PUC), whereas 150 (9%) were diagnosed with a variant histology, including 89 (5.0%), 41 (2.0%), 10 (1.0%) and 10 (1.0%) cases of micropapillary, squamous, sarcomatoid and other tumours, respectively. Variant histology was associated with the presence of adverse pathological features compared with PUC, including non‐organ‐confined disease (59% vs 38%; P < 0.001), lymph node invasion (28% vs 24%; P = 0.02), high‐grade disease (88% vs 71%; P < 0.001), tumour necrosis (28% vs 16%; P = 0.001) and positive surgical margins (15% vs 8%; P = 0.01). In competing risk analysis, micropapillary variant was the only factor associated with worse recurrence (sub‐hazard ratio [SHR] 2.27, 95% confidence interval [CI] 1.25–4.79; P = 0.02) whereas sarcomatoid variant was associated with worse CSM (SHR 16.8, 95% CI 6.86–41.17; P < 0.001).

Conclusion

We found that one out of 10 patients with UTUC treated with RNU had variant histology. Only micropapillary and sarcomatoid variants were associated with poorer oncological outcomes after adjusting for available confounding factors.
Traumatic renal injury in a UK major trauma centre – current management strategies and the role of early re‐imaging
Authors: Aldiwani Mohammed , Georgiades Fanourios , Omar Ismail , Angel‐Scott Helena , Tharakan Tharu , Vale Justin , Mayer Erik
Published: March 2019

Objectives

To analyse the contemporary management of renal injuries in a UK major trauma centre and to evaluate the utility and value of re‐imaging.

Patients and methods

The prospectively maintained ‘Trauma Audit and Research Network’ database was interrogated to identify patients with urinary tract injuries between January 2014 and December 2017. Patients’ records and imaging were reviewed to identify injury grades, interventions, outcomes, and follow‐up.

Results

Renal injury was identified in 90 patients (79 males and 11 females). The mean (sd; range) age was 35.5 (17.4; 1.5–94) years. Most of the renal traumas were caused by blunt mechanisms (74%). The overall severity of injuries was: 18 (20%) Grade I, 19 (21%) Grade II, 27 (30%) Grade III, 22 (24%) Grade IV, and four (4%) Grade V. Most patients (84%) were managed conservatively. Early intervention (<24 h) was performed in 14 patients (16%) for renal injuries. Most of these patients were managed by interventional radiology techniques (nine of 14). Only two patients required an emergency nephrectomy, both of whom died from extensive polytrauma. In all, 19 patients underwent laparotomy for other injuries and did not require renal exploration. The overall 30‐day mortality was 13%. Re‐imaging was performed in 66% of patients at an average time of 3.4 days from initial scan. The majority of re‐imaging was planned (49 patients) and 12% of these scans demonstrated a relevant finding (urinoma, pseudoaneurysm) that altered management in three of the 49 patients (6.1%).

Conclusion

Non‐operative management is the mainstay for all grades of injury. Haemodynamic instability and persistent urine leak are primary indications for intervention. Open surgical management is uncommon. Repeat imaging after injury is advocated for stable patients with high‐grade renal injuries (Grade III–V), although more research is needed to determine the optimal timing.
Oncogenic Y‐box binding protein‐1 as an effective therapeutic target in drug‐resistant cancer
Authors: Kuwano Michihiko , Shibata Tomohiro , Watari Kosuke , Ono Mayumi
Published: March 2019

Y‐box binding protein‐1 (YBX1), a multifunctional oncoprotein containing an evolutionarily conserved cold shock domain, dysregulates a wide range of genes involved in cell proliferation and survival, drug resistance, and chromatin destabilization by cancer. Expression of a multidrug resistance‐associated ATP binding cassette transporter gene, ABCB1, as well as growth factor receptor genes, EGFR and HER2/ErbB2, was initially discovered to be transcriptionally activated by YBX1 in cancer cells. Expression of other drug resistance‐related genes, MVP/LRP, TOP2A, CD44, CD49f, BCL2, MYC, and androgen receptor (AR), is also transcriptionally activated by YBX1, consistently indicating that YBX1 is involved in tumor drug resistance. Furthermore, there is strong evidence to support that nuclear localization and/or overexpression of YBX1 can predict poor outcomes in patients with more than 20 different tumor types. YBX1 is phosphorylated by kinases, including AKT, p70S6K, and p90RSK, and translocated into the nucleus to promote the transcription of resistance‐ and malignancy‐related genes. Phosphorylated YBX1, therefore, plays a crucial role as a potent transcription factor in cancer. Herein, a novel anticancer therapeutic strategy is presented by targeting activated YBX1 to overcome drug resistance and malignant progression.
A novel interleukin‐13 receptor alpha 2‐targeted hybrid peptide for effective glioblastoma therapy
Authors: Kurihara Ryohsuke , Horibe Tomohisa , Shimizu Eiko , Torisawa Aya , Gaowa Arong , Kohno Masayuki , Kawakami Koji
Published: March 2019

We previously designed and reported a novel class of drugs, namely hybrid peptides, which are chemically synthesized and composed of a targeted binding peptide and a lytic‐type peptide containing cationic amino acid residues that cause cancer cell death. In the present study, we screened for peptides that bind to interleukin‐13 receptor alpha 2 (IL‐13Rα2) by using a T7 random peptide phage display library system and isolated several positive phage clones. The A2b11 peptide, which was one of the positive clones, was shown to bind to IL‐13Rα2 protein by Biacore analysis and a binding assay using glioblastoma (GB) cell lines. This peptide was linked with a lytic peptide containing a linker sequence to form the IL‐13Rα2–lytic hybrid peptide. The IL‐13Rα2–lytic hybrid peptide showed cytotoxic activity against GB cell lines in vitro. The IL‐13Rα2–lytic hybrid peptide also affected Akt and Erk1/2 activation following treatment with interleukin‐13 and induced rapid ATP dynamics in GB cells. Anti‐tumor activity of the IL‐13Rα2–lytic hybrid peptide was observed in vivo after intratumoral injection in a mouse xenograft model of human GB cells. These results suggest that the IL‐13Rα2–lytic hybrid peptide might be a potent therapeutic option for patients with GB.
Bexarotene‐induced hypothyroidism: Characteristics and therapeutic strategies
Authors: Makita Noriko , Manaka Katsunori , Sato Junichiro , Mitani Koji , Nangaku Masaomi , Iiri Taroh
Published: March 2019

Objective

Central hypothyroidism (CH) is a well‐known adverse effect of bexarotene treatment for cutaneous T‐cell lymphoma (CTCL). While concomitant levothyroxine therapy is recommended in these cases, associations between ethnic variation or susceptibility and bexarotene‐induced CH have not yet been reported. This study aimed to characterize the kinetics and dose dependency of bexarotene‐induced CH in Japanese patients.

Design and patients

Sixty‐six Japanese patients with CTCL were retrospectively investigated by evaluating thyroid function during the early phase of bexarotene therapy.

Results

At one week after bexarotene initiation, TSH and FT4 values significantly declined. However, this effect was not bexarotene dose‐dependent at least at the dose of 96‐320 mg/m2. Approximately 1 month later, 61 patients exhibited hypothyroidism at a relatively low dose of bexarotene (average 251 mg/m2/day). Forty‐five study cases showed this effect at 1 week. Simple regression analyses indicated that higher pretreatment TSH values (at a cut‐off value of 1.30:73% sensitivity, 57% specificity) or lower normal (within the lower half of the reference range) pretreatment FT4 values (84% sensitivity, 57% specificity) were predictive of hypothyroidism at 1 week. The remaining 21 cases showed euthyroidism at 1 week, at which TSH values may roughly predict their thyroid function at 1 month (at a cut‐off value of 0.05:100% sensitivity, 80% specificity).

Conclusions

Preventive treatment with levothyroxine is recommended for Japanese CTCL patients prior to bexarotene therapy. Minimally, it should be considered for patients with a pretreatment TSH above 1.30, a lower normal pretreatment FT4, or a TSH below 0.05 at 1 week.
Angiotropism in primary cutaneous melanoma is associated with disease progression and distant metastases: A retrospective study of 179 cases
Authors: Moy Andrea P. , Duncan Lyn M. , Muzikansky Alona , Kraft Stefan
Published: March 2019

Background

Angiotropism is the histopathological correlate of pericytic mimicry and extravascular migratory metastasis (EVMM), a mechanism of melanoma spread by migration along the external surface of blood and lymphatic vessels. The frequency of angiotropism in primary cutaneous melanoma and the clinical utility of its detection remain unclear.

Methods

We investigated angiotropism in 179 primary cutaneous melanomas by hematoxylin and eosin (H&E), CD31, and S100/D240 stains.

Results

We detected angiotropism in 31 cases (17%) by H&E. CD31 immunohistochemistry increased detection to 59 cases (33%). When lymphatic vessels were included by using S100/D240 stains, 67 cases (37%) cases were positive. Angiotropism was associated with lymphatic invasion and mitotic rate with all detection methods. There was an association with increased tumor thickness when detected by H&E and CD31. No association with sentinel lymph node status was seen. By H&E and CD31 staining, angiotropism was associated with disease progression and distant metastases by univariate, but not multivariate analysis. Overall survival was not affected by the presence of angiotropism.

Conclusions

Angiotropism is relatively common in primary melanoma when immunohistochemical stains are used for detection and associated with mitotic rate and intravascular lymphatic invasion. The association with disease progression and distant metastasis suggests that it represents an alternative pathway of metastasis, that is, EVMM/pericytic mimicry vs intravascular spread.
The role of production abilities in the perception of consonant category in infants
Authors: Vilain Anne , Dole Marjorie , Lœvenbruck Hélène , Pascalis Olivier , Schwartz Jean‐Luc
Published: March 2019

The influence of motor knowledge on speech perception is well established, but the functional role of the motor system is still poorly understood. The present study explores the hypothesis that speech production abilities may help infants discover phonetic categories in the speech stream, in spite of coarticulation effects. To this aim, we examined the influence of babbling abilities on consonant categorization in 6‐ and 9‐month‐old infants. Using an intersensory matching procedure, we investigated the infants’ capacity to associate auditory information about a consonant in various vowel contexts with visual information about the same consonant, and to map auditory and visual information onto a common phoneme representation. Moreover, a parental questionnaire evaluated the infants’ consonantal repertoire. In a first experiment using /b/–/d/ consonants, we found that infants who displayed babbling abilities and produced the /b/ and/or the /d/ consonants in repetitive sequences were able to correctly perform intersensory matching, while non‐babblers were not. In a second experiment using the /v/–/z/ pair, which is as visually contrasted as the /b/–/d/ pair but which is usually not produced at the tested ages, no significant matching was observed, for any group of infants, babbling or not. These results demonstrate, for the first time, that the emergence of babbling could play a role in the extraction of vowel‐independent representations for consonant place of articulation. They have important implications for speech perception theories, as they highlight the role of sensorimotor interactions in the development of phoneme representations during the first year of life.
How do telecommunications reforms affect labour market arrangements? Evidence from Central and Western Europe
Authors: Vazquez Emmanuel , Winkler Hernan
Published: March 2019

This paper exploits variations in the timing of telecommunications reforms across Europe to investigate the relationship between the rise of alternative work arrangements and the emergence of the Internet. We evaluate whether sectors that are technologically more dependent on information and communication technologies (ICT) experienced disproportionately larger changes in their employment outcomes after telecommunications reforms were introduced. Our main results point to a disproportionate increase in total employment, part‐time work and home‐based work among ICT‐dependent sectors after the implementation of telecommunications reforms. These results suggest that telecommunications reforms affected labour market arrangements by fostering the adoption of ICT. The results are robust to several specifications.
Thoracoscopic pericardiectomy: A feasibility study and impact on cardiac volumetry in healthy horses
Authors: Silva‐Meirelles J. R. , Meirelles G. P. , de Castro M. L. , Souto A. P. F. , Brüler B. C. , Vilani R. , Guedes R. L. , Gonçalves Sousa M. , Dornbusch P. T.
Published: March 2019

This study was conceived to evaluate the feasibility of a thoracoscopic technique intended for partial pericardiectomy in horses and how cardiac volumes are influenced by such procedure in an immediate and mid‐term perspective. Thoracoscopic pericardiectomy, which is known as a minimally invasive technique, was performed in six healthy horses. Echocardiographic evaluation was performed in every horse at different times, before and after the procedure. According to the area‐length method, the following parameters were evaluated: maximum left atrial volume, minimum left atrial volume, left ventricular volume in systole and left ventricular volume in diastole. These variables were used to calculate the ejection fraction of the left atrium and left ventricle. After 28 days, repeated thoracoscopy was performed to inspect the thoracic cavity. Pericardiectomy was successfully performed in all horses, with post‐operative complication documented in only one animal. After 28 days, adhesion was observed in two animals, located between the epicardium and the thoracic wall, without however impairing cardiac function. Pericardial window was broad and well delimited in all horses, without impairing cardiac function. The thoracoscopic pericardiectomy was feasible in all horses. Although a mild reduction in cardiac volumes was documented in the first 72 h after surgery, the procedure did not impair cardiac filling and emptying in the mid‐term perspective. Future studies are warranted to investigate how this technique performs in horses with pericardial diseases.
Matrix remodelling and MMP expression/activation are associated with hidradenitis suppurativa skin inflammation
Authors: Sanchez Julia , Le Jan Sébastien , Muller Céline , François Caroline , Renard Yohan , Durlach Anne , Bernard Philippe , Reguiai Ziad , Antonicelli Frank
Published: March 2019

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle, associated with considerable tissue remodelling. Although abnormal cytokine expression was detected both in perilesional and in uninvolved skin, up to now there is no model allowing a better understanding of the implicit inflammatory mechanisms in HS. The aim of this study was to investigate the inflammatory response in HS skin by mean of an ex vivo model culture. To that purpose, nine skin biopsy specimens from patients suffering from HS and controls were cultured up to 4 days. Microscopy imaging investigations showed variations of collagen I and III organization, and an increase in elastin fibres fragmentation in HS skin after 4 days of culture. The HS matrix structure remodelling was associated with high level of MMP‐2 and MMP‐9 in HS lesional skin. After 4 days of culture, the MMP expression in HS perilesional skin reached the level observed in HS lesional skin. Concomitantly, an increase in IL‐1β concentration was observed in all skin samples after 4 days of culture, although IL‐1β concentrations remained significantly higher in HS lesional skin as compared with control skin. Meanwhile, neither IL‐17 concentrations nor the inflammasome components NLRP3 and caspase‐1 varied. Thus, our HS skin model culture showed that MMP‐induced matrix alteration could participate in HS inflammation by releasing biological active peptides and inflammatory factors from the extracellular matrix (ECM), and open new opportunities to investigate the regulation of the inflammatory mechanism associated with HS.
A potential link between desmoglein 3 and epidermal growth factor receptor in oral squamous cell carcinoma and its effect on cetuximab treatment efficacy
Authors: Minabe Masaki , Akiyama Yurie , Higa Kazunari , Tachikawa Tetsuhiko , Takahashi Shinichi , Nomura Takeshi , Kouno Michiyoshi
Published: March 2019

Desmoglein (DSG) 3 is overexpressed in oral squamous cell carcinoma (OSCC). Epidermal growth factor receptor (EGFR) inhibitor cetuximab is widely used for OSCC treatment. Several evidences suggest a correlation between DSG3 and EGFR in epidermal keratinocytes. EGFR inhibition has been shown to enhance cell‐cell adhesion and induce terminal differentiation in epidermal cells. Thus, here we investigated the DSG3‐EGFR interaction in OSCC and its effect on cetuximab treatment. Cell lines established from the primary tumor and metastatic lymph nodes of four OSCC patients and three commercial OSCC cell lines were used for the experiments. Cells from metastatic lymph nodes of each patient expressed increased DSG3 and EGFR than cells from the primary tumor in the same patient. Cetuximab treatment increased DSG3 expression by up to 3.5‐fold in seven of the 11 cell lines. A high calcium concentration increased the expression of DSG3 and EGFR in a dose‐dependent manner. Strikingly, a high calcium‐associated DSG3 induction enhanced cetuximab efficacy by up to 23% increase in cetuximab‐low‐sensitive cell lines. Our findings also suggest a correlation between DSG3 and EGFR in OSCC, and this affects cetuximab treatment efficacy.
Therapist Interventions Associated with Productive Emotional Processing in the Context of Attachment‐Based Family Therapy for Depressed and Suicidal Adolescents
Authors: Tsvieli Noa , Nir‐Gottlieb Ofir , Lifshitz Chen , Diamond Guy S. , Kobak Roger , Diamond Gary M.
Published: March 2019

Productive emotional processing is considered a key change mechanism in attachment‐based family therapy (ABFT). This study examined the impact of attachment‐based family therapy therapist interventions aimed to promote productive emotional processing of primary adaptive emotions in a sample of 30 depressed and suicidal adolescents who had participated in a larger randomized clinical trial. Results of sequential analyses revealed that relational reframes and therapists’ focus on primary adaptive emotions were associated with the subsequent initiation of adolescents’ productive emotional processing of primary adaptive emotions. In contrast, interpretations, reassurances, and therapists’ focus on adolescents’ rejecting anger toward their parents were all followed by the discontinuation of adolescents’ emotional processing that had already begun. Finally, therapists’ general encouragement of affect and focus on adolescents’ unmet attachment/identity needs were associated with both the initiation of adolescents’ productive emotional processing, and with the discontinuation of such processing once it had already begun. Theoretical and clinical implications are discussed.
Helicobacter pylori urease induces pro‐inflammatory effects and differentiation of human endothelial cells: Cellular and molecular mechanism
Authors: de Jesus Souza Mariele , de Moraes João Alfredo , Da Silva Vany Nascimento , Helal‐Neto Edward , Uberti Augusto Frantz , Scopel‐Guerra Adriele , Olivera‐Severo Deiber , Carlini Célia R. , Barja‐Fidalgo Christina
Published: March 2019

Background

Helicobacter pylori urease (HPU) is a key virulence factor that enables bacteria to colonize and survive in the stomach. We early demonstrated that HPU, independent of its catalytic activity, induced inflammatory and angiogenic responses in vivo and directly activated human neutrophils to produce reactive oxygen species (ROS). We have investigated the effects of HPU on endothelial cells, focusing on the signaling mechanism involved.

Methods

Monolayers of human microvascular endothelial cells (HMEC‐1) were stimulated with HPU (up to 10 nmol/L): Paracellular permeability was accessed through dextran‐FITC passage. NO and ROS production was evaluated using intracellular probes. Proteins or mRNA expressions were detected by Western blotting and fluorescence microscopy or qPCR assays, respectively.

Results

Treatment with HPU enhanced paracellular permeability of HMEC‐1, preceded by VE‐cadherin phosphorylation and its dissociation from cell‐cell junctions. This caused profound alterations in actin cytoskeleton dynamics and focal adhesion kinase (FAK) phosphorylation. HPU triggered ROS and nitric oxide (NO) production by endothelial cells. Increased intracellular ROS resulted in nuclear factor kappa B (NF‐κB) activation and upregulated expression of cyclooxygenase‐2 (COX‐2), hemeoxygenase‐1 (HO‐1), interleukin‐1β (IL‐1β), and intercellular adhesion molecule‐1 (ICAM‐1). Higher ICAM‐1 and E‐selectin expression was associated with increased neutrophil adhesion on HPU‐stimulated HMEC monolayers. The effects of HPU on endothelial cells were dependent on ROS production and lipoxygenase pathway activation, being inhibited by esculetin. Additionally, HPU improved vascular endothelial growth factor receptor 2 (VEGFR‐2) expression.

Conclusion

The data suggest that the pro‐inflammatory properties of HPU drive endothelial cell to a ROS‐dependent program of differentiation that contributes to the progression of H pylori infection.
The relationship between person–team fit with supervisor–subordinate guanxi and organizational justice in a Chinese state‐owned enterprise
Authors: Zhang Shanshan , Liang Jieshuang , Zhang Jianxin
Published: March 2019

The study examines how subordinates’ perceptions of justice in Chinese working teams are influenced by the person–team fit (or the misfit) of the supervisor–subordinate guanxi (SSG). We tested our hypotheses on a sample of 1,086 employees from 149 work groups in one state‐owned enterprise; using a combination of cross‐level polynomial regression and response surface analysis. The results showed that subordinates’ perceptions of justice, in terms of procedural, interactional, and distributive justice, were higher when individual SSG was congruent with the average SSG in the team (TSSG) at a high level than when an individual SSG was congruent with TSSG at a low level. Meanwhile, in the misfit situation, subordinates’ perceptions of the three dimensions of justice were higher when the individual SSG relative to TSSG (relative SSG, or RSSG) was surplus (individual SSG exceeded TSSG) versus RSSG deficient (TSSG exceeded individual SSG). Nevertheless, the subordinates’ perceptions of distributive justice were the highest when SSG and TSSG were almost equal in high level, as observed by integrating the fit with the misfit line. These findings highlight the important boundary cultural conditions of the psychological processes of justice and provide useful insights for international managers conducting their business in China.
Retrospective pharmaceutical financial benefits and cost avoidance analysis of clinical trial participation in the Australian haematology setting
Authors: Truong Kelvin , Kwan Yiu Lam , Nigro Lucia , Huseincehajic Admir , Trotman Judith
Published: March 2019

Background

Clinical trial participants receiving investigational new drugs, which subsequently become approved by a medicines regulatory authority for its trialled indication, effectively gain free early access to efficacious treatment. Participants may also benefit from receiving approved, but unsubsidised medicines. These financial benefits of clinical trial participation have not previously been defined or quantified. Additionally, there are limited Australian pharmaceutical cost avoidance studies quantifying government savings through sponsored clinical trials.

Aims

To calculate pharmaceutical financial benefits and cost avoidance of clinical trial participation at a single Clinical Research Unit.

Methods

Recruiting clinical trials between 1 January 2006 and 31 December 2017 conducted at the Haematology Clinical Research Unit, Concord Repatriation General Hospital, Sydney were reviewed. Dispensing records were used to quantitate the pharmaceuticals dispensed to every participant. Financial calculations were based on Pharmaceutical Benefits Scheme (PBS) pricing, or from UpToDate for non‐PBS listed agents.

Results

Thirty‐six eligible clinical trials involving 245 participants accrued AU$3 971 357 in financial benefit from early access to subsequently approved investigational new drugs, AU$12 209 538 in financial benefit from accessing approved medications not PBS listed, and AU$6 728 576 in government cost avoidance. These findings totalled AU$22 909 471, 89% of which was derived in the past 5 years.

Conclusion

Pharmaceutical financial benefit is a previously unquantified aspect of clinical trial participation, its assigned value reflecting a measure of the quality and quantity of life delivered to patients. These data, albeit from a single discipline and institution, suggest that financial benefit represents a greater value than cost avoidance, and that its inclusion in cost‐analyses may better reflect the monetary benefits of accessing efficacious pharmaceutical agents through clinical trials.
Management of stroke in the Australian Indigenous population: from hospitals to communities
Authors: Tiedeman Clare , Suthers Belinda , Julien Benjamin , Hackett Anna , Oakley Patrick
Published: March 2019

Background

Ischaemic strokes lead to significant morbidity and mortality within the Australian Indigenous population, with known variances in the management of strokes between indigenous and non‐indigenous populations.

Aims

To compare investigations and management of indigenous and non‐indigenous patients presenting to a New South Wales rural referral hospital with an ischaemic stroke to the national stroke standards across inpatient and outpatient settings.

Methods

Historical cohort study of 43 indigenous and 167 non‐indigenous patients admitted to Tamworth Rural Referral Hospital with an ischaemic cerebrovascular accident.

Results

Indigenous patients were significantly less likely to have investigations completed, including carotid imaging (93.8% vs 100%, P = 0.012) and echocardiography (73.3% vs 97.7%, P = 0.004). Discharge follow up was significantly lower for the indigenous population (74.4% vs 87.4%, P = 0.034). Indigenous stroke patients were 15.8 years younger than non‐indigenous subjects (56.8 vs 72.6 years old; P < 0.001). Indigenous patients were more likely to have stroke risk factors, including smoking (51.2% vs 15.0%; P < 0.001), diabetes mellitus (37.2% vs 16.8%, P = 0.003) and past history of cerebrovascular accident or transient ischaemic attack (50.2% vs 31.1%, P = 0.032).

Conclusions

The investigation and post‐discharge care of indigenous ischaemic stroke patients is inferior to non‐indigenous patients. Indigenous patients within rural NSW have a higher prevalence of preventable disease, including those that confer a higher stroke risk. Further research is needed to investigate the cause of these discrepancies and to improving indigenous stroke care between hospitals and primary care providers.
Epicardial‐endocardial breakthrough site ablation: Demonstration of alternative target for perimitral atrial tachycardia
Authors: Sato Yoshikazu , Kusa Shigeki , Hachiya Hitoshi , Iesaka Yoshito
Published: March 2019

A 62‐year‐old man underwent the catheter ablation for persistent atrial tachycardia (AT) with a cycle length of 357 milliseconds. An ultrahigh resolution mapping revealed that this tachycardia was a clockwise perimitral AT despite the conduction was apparently blocked across the lateral mitral isthmus line both at the endocardium and within the coronary sinus. The AT was terminated by the single radiofrequency application at the site below the mitral isthmus line where the endocardial activation breakout was seen. This case suggests that the epicardial‐endocardial conduction breakthrough site may be an alternative ablation target in a difficult ablation case of perimitral AT.
The fourth cryoballoon generation with a shorter tip to facilitate real‐time pulmonary vein potential recording: Feasibility and safety results
Authors: Straube Florian , Dorwarth Uwe , Pongratz Janis , Brück Benedikt , Wankerl Michael , Hartl Stefan , Hoffmann Ellen
Published: March 2019

Introduction

Time‐to‐isolation (TTI) guided ablation protocols have been developed to ensure durable pulmonary vein isolation (PVI) in cryoballoon ablation (CBA). The aim was to determine the feasibility and safety of the fourth generation cryoballoon (CBG4) with a shortened tip.

Methods and Results

Consecutive patients scheduled for initial atrial fibrillation (AF) ablation were prospectively included. PVI with the 28 mm CBG4 and the latest 20 mm spiral‐mapping catheter (SMC) was performed.

A total of 302 pulmonary veins (PVs) in 76 patients (64.8 ± 10.4 years, paroxysmal AF 49%) were treated with 617 applications. Left atrium (LA) time, fluoroscopy time, and dose‐area product were 65.5 ± 19.2 minutes, 14.6 ± 5.6 minutes, and 1094 (738; 2097) cGy·cm2, respectively. PVI in cryoballoon technique was achieved in 302 of 302 (100%) PVs. TTI was determined in 256 (84.8%) of PVs. The mean TTI was 45.3 ± 26.4 seconds. Single‐shot isolation was achieved in 247 (82%) PVs. In 6 of 302 (2.0%) PV the SMC was changed to a stiff wire to isolate the PV because of instability, and in 17 of 302 (5.6%) of PVs, the 23 mm CB was used to isolate. No radiofrequency touch‐up applications were applied. The mean nadir balloon temperature was −44.8°C ± 6.6°C. Balloon dislodgement during positioning occurred in 3 of 617 (0.5%) applications without complications. One PN palsy occurred which resolved until discharge. One patient suffered from the inflammatory syndrome.

Conclusion

The CBG4 with a shorter distal tip seems to be safe and effective, and allows determining the TTI in 84.8% of PVs. In case of balloon instability, the exchange of the SMC to a stiff wire or, in small PV, the 23 mm cryoballoon facilitate PVI.