bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing implicit and explicit dementia stigma in young adults and care-workers
Authors: Kane Alan , Murphy Carol , Kelly Michelle
Published: October 2018

This aim of this study was to assess implicit and self-reported stigma towards people with dementia in young adults with no contact or experience ( n = 23), and in care-workers ( n = 17 professional dementia care-workers). Data were analysed to determine whether stigma was related to self-reported levels of depression, anxiety, stress and professional burnout. Forty participants completed the Implicit Relational Assessment Procedure and Dementia Attitudes Scale. The Depression Anxiety and Stress Scale and Maslach Burnout Inventory were used to measure depression, anxiety, stress and professional burnout. The young adult group showed statistically significant levels of dementia stigma (on the two “ dementia” trial-types, p = .027 and p = .030). Statistical analyses showed more dementia-positive attitudes in care-workers compared to young adults on the Implicit Relational Assessment Procedure and the Dementia Attitudes Scale (both p’s=.021). Spearman’s Rho correlations tests showed that for the care-givers, higher levels of burn-out were associated with more negative attitudes towards people with dementia on both of the Dementia Attitudes Scale subscales (social comfort p<.001 and dementia knowledge p=.005). The results support prior research showing that experience with a stigmatised group can lower stigma and demonstrate the importance of providing a supportive work environment to mitigate burnout.
Exploring inter-organizational paradoxes: Methodological lessons from a study of a grand challenge
Authors: Jarzabkowski Paula , Bednarek Rebecca , Chalkias Konstantinos , Cacciatori Eugenia
Published: October 2018

In this article, we outline a methodological framework for studying the inter-organizational aspects of paradoxes and specify this in relation to grand challenges. Grand challenges are large-scale, complex, enduring problems that affect large populations, have a strong social component and appear intractable. Our methodological insights draw from our study of the insurance protection gap, a grand challenge that arises when economic losses from large-scale disaster significantly exceed the insured loss, leading to economic and social hardship for the affected communities. We provide insights into collecting data to uncover the paradoxical elements inherent in grand challenges and then propose three analytical techniques for studying inter-organizational paradoxes: zooming in and out, tracking problematization and tracking boundaries and boundary organizations. These techniques can be used to identify and follow how contradictions and interdependences emerge and dynamically persist within inter-organizational interactions and how these shape and are shaped by the unfolding dynamics of the grand challenge. Our techniques and associated research design help advance paradox theorizing by moving it to the inter-organizational and systemic level. This article also illustrates paradox as a powerful lens through which to further our understanding of grand challenges.
Talent Development in China: Current Practices and Challenges Ahead
Authors: Wang Jia , Sun Jian-Min
Published: October 2018

The Problem

The continuing trend of globalization has made the need for talent a worldwide issue. China, as one of the fastest growing economies and population in the world, has made unprecedented growth during the past few decades. Nevertheless, with a rapidly aging population, migrant workers demanding better pay, rising numbers of college graduates entering the job market, and exacerbating shortage of technical managerial talents, China is facing serious new human resource challenges.

The Solution

In this article, we analyzed China’s talent needs and examined its current talent development practice. To gain deep insights, we classified Chinese human resources by industries (primary, secondary, and tertiary), geographical regions (Eastern, Central, and Western), and organizational ownership (private vs. state-owned). By taking this contingency-based approach, we hope to capture the uniqueness and complexity of the contextual variables that influence talent development in China. This research contributes to Chinese management literature and also expands global talent development knowledge base.

The Stakeholders

The findings and recommendations offered in this article will benefit multiple stakeholders, including national policy makers in China, domestic and multiple-national organizational leaders, human resource or talent development practitioners, and researchers.
Airflow resistance of acoustical fibrous materials: Measurements, calculations and applications
Authors: Tang Xiaoning , Yan Xiong
Published: October 2018

The acoustic performance of fibrous materials is mainly determined by its airflow resistance, and it is a parameter of the resistance that the airflow meets through the materials. This paper has summarized the recent advances on the measurements, calculations and applications of airflow resistance. Firstly, different methods for airflow resistance measurements are presented, mainly including the direct airflow method, alternating airflow method and acoustical method. We have summarized the development history, current status and industrial applications of these methods. Secondly, this paper has summarized the models of calculating airflow resistance. Most of these empirical models are based on the characteristic parameters of fibrous materials, for instance bulk density, fiber diameter, porosity and thickness. Thirdly, this review has gathered the applications of airflow resistance in sound absorption and noise control. It is a crucial parameter in the prediction of both normal incidence sound absorption and reverberation chamber sound absorption. In conclusion, this review has concluded with some perspectives for the measurements, calculations and applications of airflow resistance.
Strategies for Supporting Smoking Cessation Among Indigenous Fathers: A Qualitative Participatory Study
Authors: Bottorff Joan L. , Sarbit Gayl , Oliffe John L. , Caperchione Cristina M. , Wilson Danielle , Huisken Anne
Published: October 2018

There is a need for tailored smoking cessation programs specifically for Indigenous fathers who want to quit smoking.The aim of this study was to engage Indigenous men and key informants in guiding cultural adaptations to the Dads in Gear (DIG) cessation program. In Phase 1 of this qualitative participatory study, Indigenous men were engaged in group sessions and key informants in semistructured interviews to gather advice related to cultural adaptations to the DIG program. These data were used to guide the development of program prototypes. In Phase 2, the prototypes were evaluated with Indigenous fathers who were using tobacco (smoking or chewing) or were ex-users. Data were analyzed inductively. Recommendations for programming included ways to incorporate cultural values and practices to advance men’s cultural knowledge and the need for a flexible program design to enhance feasibility and acceptability among diverse Indigenous groups. Men also emphasized the importance of positive message framing, building trust by providing “honest information,” and including activities that enabled discussions about their aspirations as fathers as well as cultural expectations of current-day Indigenous men. That the Indigenous men’s level of involvement with their children was diverse but generally less prescriptive than contemporary “involved fathering” discourse was also a key consideration in terms of program content. Strategies were afforded by these insights for meeting the men where they are in terms of their fathering—as well as their smoking and physical activity. This research provides a model for developing evidence-based, gender-specific health promotion programs with Indigenous men.
Experimental and numerical study on the performance of an axial fan with a Gurney flap
Authors: Chen Liu , Xie Haijun , Xu Jun , Dai Ren , Chen Jian
Published: October 2018

Gurney flap is a miniature lift-enhancement device installed at the airfoil trailing edge and has been successfully applied to fixed wing aircraft and low-speed horizontal wind turbines. In this article, Gurney flap is extended to increase pressure output of a diffusive cascade flow in rotating turbomachinery, which is complicated for its three dimensionalities and diffusive separation characteristics. Wind tunnel tests and computational fluid dynamic simulations were accomplished on an axial fan profiled with an NACA 65-(12)10 airfoil to investigate the effects of Gurney flap on the performance of a high solidity. We present the detailed flow features of the fan with and without Gurney flap after validating the simulation results with the experimental datum. The experimental results show positive Gurney flap effects on fan’s pressure rise and flow rate improvement. However, negative Gurney flap effects on fan’s efficiency are more evident than Gurney flap on isolated airfoils. Detailed flow field analysis from computational fluid dynamic computation reveals that the increased airfoil pressure loading along the fan blade chord strengthens the tip leakage flow, which induces more tip second flow losses than in the baseline fan. In addition to the positive lift enhancement, the net Gurney flap effect in diffusion cascade is influenced by the three-dimensional flow structure.
A study on launch site ground of vehicle-mounted missile based on elastic layer theory
Authors: Zhao Liangyu , Jiang Yi
Published: October 2018

With the widespread use of the vehicle-mounted missile launching system, the research of launch site ground becomes very important. The loading of missile launch system under the supporting disk is similar to inverted bell, and its radius and size of the missile launching are much more than a car. So the ready-made equivalent modulus formula under the action of circular uniformly distributed loading is not suitable for the calculation of launch site ground of vehicle-mounted missile. Therefore, based on the elastic layered system and the Gauss–Legendre numerical calculation method, a new calculation method of equivalent modulus is proposed, as well as the regression formulation for calculation of equivalent modulus of foundation is also shown. Based on the above analysis, a launch site ground mechanical model is presented. The thin plate model on elastic half-space foundation was formulated taking into account normal direction and the double-layer elastic system model was proposed for in tangential direction. Validity of the model was done by coring the programming calculation with the finite element numerical simulation for selected cases.
Immunohistochemical Analysis of Human Lung Cancers with Anti-ras p21 Monoclonal Antibodies
Authors: Dosaka Hirotoshi , Harada Masao , Kuzumaki Noboru , Kobayashi Hitoshi , Isobe Hiroshi , Miyamoto Hiroshi , Kawakami Yoshikazu
Published: October 2018

The expression of ras oncogene product p21 in human malignant pleurisy and primary lung cancer was studied immunocyto-histochemically with monoclonal antibodies (MoAbs) rp-28 and rp-35 against ras p21. In pleural effusion cells, cancer cells revealed more intensively positive reaction with MoAb rp-35 than with MoAb rp-28, especially in the plasma membrane, and no positive reaction was obtained in any kind of inflammation cells with the exception of faintly positive reaction in the cytoplasm of macrophages.

In primary lung cancers, well or moderately differentiated adenocarcinoma tissues showed higher reactivity with MoAb rp-28 than those of poorly differentiated adenocarcinoma or any other histological subtype of lung cancer. With MoAb rp-35, intensively positive reaction was obtained in most of cases with all different histological subtypes of lung cancer. The staining in cancer cells was usually localized intensively to the plasma membrane and weakly to the cytoplasm with both MoAbs. Normal bronchial epithelial and glandular tissues showed only cytoplasmic staining. These two MoAbs, especially MoAb rp-35, may be useful in clinicopathological applications for the diagnosis of malignant pleurisy and primary lung cancer.
Intermediate-sized Filament Proteins (Keratin, Vimentin, Desmin) in Metaplastic Carcinomas, Carcinosarcomas and Stromal Sarcomas of the Breast
Authors: Santini Donatella , Bazzocch Floriano , Paladini Giuseppe , Gelli Maria Carolina , Ricci Monica , Mazzoleni Guido , Martinelli Giuseppe
Published: October 2018

The distribution of intermediate-filament (IF) proteins of the keratin, vimentin and desmin type in breast stromal sarcomas, carcinosarcomas, metaplastic carcinomas and phyllodes tumors has been compared using the avidin-biotin complex immunoperoxidase technique. Keratin reactivity was found in carcinomatous and pseudosarcomatous areas of all metaplastic carcinomas, in the cuboidal epithelial cells of carcinosarcomas and in the epithelial component of phyllodes tumors. Vimentin and desmin were detected in the sarcomatous portion of carcinosarcoma, focally in the stromal component of phyllodes tumors and not always in the stromal sarcomas. These data confirm that combined analysis of IF expression is a reliable and convincing way to differentiate stromal sarcomas, metaplastic carcinomas and carcinosarcomas in breast pathology.
A New ADP-ribosyltransferase in Human Serum: Significance in Cancer
Authors: Pohl Adolf L.
Published: October 2018

A novel ADP-ribosyltransferase (ADPRT) is reported from sera of both healthy human subjects (n = 25) and patients with colorectal tumors (n = 12) and breast cancer (n = 55). In sera of healthy controls (n = 25) the average ADPRT values were 250 ± 56 picokatal/liter. ADPRT serum activities in metastatic cancer patients (n = 47) were three times higher (p < 0.01) than in normal controls. A tumor origin of the serum ADPRT can be inferred from the statistical correlation (R = 0.74) between tumor and serum levels. The radiometric test procedure (CV 20–25%) is critically validated and kinetic properties of serum ADPRT have been studied, showing a competitive inhibition by nicotinamide, benzamide and 3-aminobenzamide.

The kinetic parameters of serum ADPRT resemble those reported for nuclear ADPRT, thus indicating that serum ADPRT activity could be due to a nuclear enzyme released from the tumor cells.
CEA Levels in Gastric Juice in Precancerous Conditions and Cancer
Authors: Amador Dino , Ravaioli Alberto , Biserni Roberta , Bonaguri Chiara , Erbacci Paola , Pallotti Gualtiero , Ronchi Anna , Saragoni Ariele , Falcini Fabio
Published: October 2018

First described in 1965 as a specific antigen for cancer of the colon, CEA is now considered to be an antigen associated with many types of malignant neoplasia, although the CEA-Test's role in clinical routine has yet to be clearly defined.

In the present study CEA levels in gastric juice were measured in subjects with gastric carcinoma (n = 25) and with benign gastric lesions (n = 171). CEA was significantly (p < 0.05) higher in patients with gastric carcinoma (GC) than in subjects with benign gastric lesions, other than chronic atrophic gastritis (CAG) associated with intestinal metaplasia (IM). In this latter condition CEA levels were similar to those in patients with GC.

These results suggest that the assay of CEA in gastric juice could be included in the diagnostic program for gastric cancer and its precursors with the aim of assessing its utility as risk indicator in the management of precancerous conditions and lesion.
The Biological Tumor Markers' Myopia: A Model with CA 125 and Second-look in Ovarian Cancer
Authors: Zanaboni Flavia , Accinell Giuseppe , Colombo Pietro , Jelmoni Giorgio , Morandi Cesare , Pedronetto Sergio , Sbernini Rosolino , Bolis Giorgio
Published: October 2018

Preoperative CA 125 levels were measured in 36 patients with advanced epithelial ovarian carcinoma in clinical response undergoing a second-look operation. All the patients had positive levels (> 35 U/ml) of this tumor marker at diagnosis. The correlation between antigen levels and disease status at surgery revealed a sensitivity of this assay of 0.55 (only 11/20 patients still with tumor had positive levels) and a specificity of 0.94 (15/16 patients with no tumor had < 35 U/ml). The predictive value of a positive test was 0.92. This method unfortunately proved unable to recognize microscopic residual tumor burden, less than 0.5 cm.
Clinical Assay of Serum SCC-Ag in Urothelial Cancers
Authors: Takahashi Y. , Shinoda I. , Takeuchi T. , Kuriyama M. , Ban Y. , Kawada Y.
Published: October 2018

Serum squamous cell carcinoma related antigen (SCC-Ag) values were determined in 86 patients with urothelial cancers. Mean + standard deviation for serum SCC-Ag. was 3.4 ± 0.98 ng/ml and positive values (> 2.0 ng/ml) were found in 27%. Neither pathological stage nor cell grade of the urothelial cancer showed any relation to serum SCC-Ag. Serum SCC-Ag. changed parallel to the clinical course. These results suggest that, as there is no specific tumor marker in urothelial cancer, serum SCC-Ag. may be a useful aid in diagnosing cancer and monitoring these patients. Used together with another non-specific marker, an increase in the accuracy of diagnosis of these malignancies can be expected.
Individually Specified Drug Immunoconjugates in Cancer Treatment
Authors: Oldham R.K. , Lewis M. , Orr D.W. , Liao S-K. , Ogden J.R. , Hubbard W.H. , Birch R.
Published: October 2018

Forty-three patients with disseminated refractory malignancies each received an individually-specified combination of either Adriamycin (24 patients) or mitomycin-C (19 patients) conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously.

Seventeen out of twenty-four patients had reactions to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritis and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression.

Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C patients.

Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors and colon with likely drug induced colitis seen after colon binding. This study demonstrates the feasibility and illustrates technical considerations in preparing drug immunoconjugate cocktails for patients with refractory malignancies.

Cocktail formulation and antibody delivery was accomplished. The major technical hurdle appears to be the selection of effective conjugation methods that can be used to optimally bind drugs to monoclonal antibodies for targeted cancer therapy.
Distribution of CA 125 in Placental Tissues
Authors: Fuith L.C. , Müller-Holzner E. , Marth C. , Perkmann E. , Zeimet A. , Daxenbichler G.
Published: October 2018

The presence of the tumor marker CA 125 was studied in different compartments of the human placenta. Levels of CA 125 in the cytosol of chorionic villi ranged from 27 - 17100 U/g (median 560 U/g). In the placental amnion and chorion concentrations ranged from 175-29000 U/g, median 1060 U/g and were not statistically different. In the umbilical cord values were significantly lower (range 44 - 7600 U/g; median 180 U/g).

Maternal serum probes were above the upper limit of normal in all cases (range 48 - 500 U/ml; median 131 U/ml). Immunohistochemistry detected CA 125 exclusively within the amniotic cells of the placenta and the umbilical cord. This might be because CA 125 fixes more to insoluble structures in the amnion or because of contamination of chorionic villi with the underlying decidua.
Clinical Behaviour of Prostatic Specific Antigen and Prostatic Acid Phosphatase: A Comparative Study
Authors: Robles J. Morote , Morell A. Ruibal , De Torres Mateos J.A. , Roselló A. Soler
Published: October 2018

We assayed prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels in 1383 patients using a double antibody radioimmunoassay (RIA) I125. Establishing the upper normal limit in 10 ng/ml PSA and 2.5 ng/ml for PAP, the false positive results were only 1.9 and 5.1 percent in men with non-prostatic benign or malignant pathology and respectively 0 and 2.2 percent in women. We detected false positive levels for these two tumoral markers in 3.5 and 4.7 percent of patients with non-complicated benign prostatic hypertrophy, 64.8 and 19.2 percent in complicated benign prostatic hypertrophy, 24 and 16 percent in acute prostatitis and 3.3 percent in chronic prostatitis.

The sensitivity in patients with prostate cancer was 87.2 percent for PSA and 64.1 percent for PAP, and there was a better correlation with PSA than PAP for tumoral spread and histological grading. Finally, clinical efficacy was higher with PSA and was no better when both markers were assayed.
Diagnosis of Bone and Liver Metastases in Breast Cancer Comparing Tumor Markers and Imaging Techniques
Authors: Zanco P. , Rota G. , Sportiello V. , Borsato N. , Ferlin G.
Published: October 2018

One hundred and forty-seven patients were examined by bone scintigraphy, ultrasonography and scintigraphic scan of the liver, at different times after surgical removal of a breast cancer, to rule out skeletal and hepatic metastases. At the same time as imaging procedures, serum levels of tumor markers (CEA, TPA and CA 15–3) were determined using radioimmunometric methods. One or more markers were elevated in all 13 patients with hepatic metastases; 9 out of 46 patients with bone metastases had all serum markers normal, with a sensitivity of 80%. Combined assay of the markers proved useful, TPA and CA 15–3 showing the best sensitivity in bone metastases, and all three markers in liver metastases.
Detection of Lewisa antigen in sera of ovarian carcinoma patients by MOv2-MOv8 double-determinant radioimmunoassay
Authors: Mantovani L. , Azzini V. , Canevari S. , Danzi R. , Fontanelli R. , Leoni F. , Ménard S. , Miotti S. , Pasquali M. , Zambetti M. , Colnaghi M.I.
Published: October 2018

The monoclonal antibodies MOv2 and MOv8, raised against ovarian carcinoma, were found to be directed against two non-crossreacting epitopes expressed on the same molecule. Immunochemical analysis of the MOv8 recognized epitope showed that the Lea oligosaccharide, or commercial anti-Lea MAb, but not the anti-Leb MAb, prevented MOv8 binding to the reference target cell line (SW626), indicating that it is carried by the Lea antigen. Since we previously reported that MOv2 also recognises the Lea antigen, these data suggest that Mov8 and Mov2 were directed against different epitopes on the same oligosaccharide chain. Bearing in mind the knowledge of the biochemical nature of the monoclonal antibody recognized epitopes (CaMOv2 and CaMOv8), the presence of the circulating molecules recognized by them was analyzed by double determinant immunoradiometric assay (DDIRMA) in 103 sera from ovarian carcinoma patients. Patients with clinical evidence of the disease (ED) with MOv2 and MOv8 reactive and negative tumors had sera reactivity in 67% and 19% respectively. Also, 26% of the patients with no clinical evidence of disease (NED) had positive sera. When we investigated the relationship between MOv2-MOv8 DDIRMA sera positivity and red blood cells (RBC) Lewis phenotype, a strong correlation was found between the Lea+ phenotype and DDIRMA sera reactivity in healthy donors (6/6) and in ovarian carcinoma patients (9/10) whatever their clinical condition. No Lea healthy donors gave evidence of MOv2-MOv8 reactive sera. In contrast, 33% and 57% of the sera from ED carcinoma patients with respectively Leab+ and Leab phenotype were positive.

In conclusion, the percentage of DDIRMA positive cases previously reported in healthy donors and found here in ovarian carcinoma patients with MOv2 and MOv8 negative tumors or NED, was in agreement with Lea + phenotype frequency in the normal Caucasian population. However the Lewisa could represent a tumor-associated antigen in ED patients with Lea phenotype and MOv2-MOv8 DDIRMA might be useful for monitoring the disease
Experimental pancreatic adenocarcinoma: An immunohistochemical study for CA 19-9 and its correlation with serum levels
Authors: Abad M. , Paz J.I. , Pedraz M.J. , Muñoz E. , Bullón A.
Published: October 2018

Experimental pancreatic carcinoma induced in Golden Syrian Hamsters by subcutaneous injections of N-nitrosobis-(2-oxopropyl) amine (BOP) was studied during the different phases of its development by determination of serum CA 19-9 levels and tissue labeling with CA 19-9 TM. Significant differences were observed in the CA 19-9 values between the controls and animals with carcinoma (p < 0.01) and between the latter and animals with cystic or cystic papillary lesions (p < 0.01). Distribution of the deposits of CA 19-9 TM was different in the initial tumoral lesions and in the longer-developed tumors. An important correlation was observed between tissue deposits and serum levels of this tumor marker.
Challenges for the Dynamic Functional Model of Jealousy
Authors: D’Arms Justin
Published: October 2018

This comment on Chung and Harris presses for a clearer account of the motivational role of jealousy within the dynamic functional model of jealousy. It also calls into question the inclusion of “elaborated” jealousy within the emotion itself. It argues that differentiating emotional motivation from motivation toward the same goal that an emotion has requires additional resources.
In the wake of a terrorist attack, do Americans’ attitudes toward Muslims decline?
Authors: Boydstun Amber E. , Feezell Jessica T. , Glazier Rebecca A.
Published: October 2018

When a terrorist attack occurs, a natural response may be increased public concern about terrorism. But when a self-described Muslim perpetrates a terrorist attack, do negative attitudes toward Muslims also increase? If so, is this effect conditional on the nature of people’s past personal experiences with Muslims? We present natural experiment data based on a 2015 web-based survey of 2105 non-Muslims in the US, a survey that happened to span the terrorist attacks in Paris on 13 November and San Bernardino on 2 December. We thus test Americans’ feelings toward Muslims immediately before and after both an international and a domestic terrorist attack. We find that, although the attacks significantly affected Americans’ concerns about radicalism both in the US and abroad, they did not negatively affect Americans’ thermometer feelings toward Muslims in the aggregate—a null finding conditioned only slightly by the nature of past personal experiences with Muslims.
Factors Associated With Interstage Mortality Following Neonatal Single Ventricle Palliation
Authors: Alsoufi Bahaaldin , McCracken Courtney , Kochilas Lazaros K. , Clabby Martha , Kanter Kirk
Published: October 2018

Background:

Several advances have led to improved hospital survival following neonatal palliation (NP) of single ventricle (SV) anomalies. Nonetheless, a number of patients continue to suffer from interstage mortality (ISM) prior to subsequent Glenn. We aim to study patients’ characteristics and anatomic, surgical, and clinical details associated with ISM.

Methods:

A total of 453 SV neonates survived to hospital discharge following NP. Competing risk analysis modeled events after NP (Glenn, transplantation, or death) and examined variables associated with ISM.

Results:

Competing risk analysis showed that one year following NP, 10% of patients had died, 87% had progressed to Glenn, 1% had received heart transplantation, and 2% were alive without subsequent surgery. On multivariable analysis, factors associated with ISM were as follows: weight ≤2.5 kg (hazard ratio, HR = 2.4 [1.2-4.6], P = .013), premature birth ≤36 weeks (HR = 2.0 [1.0-4.0], P = .05), genetic syndromes (HR = 3.2 [1.7-6.1], P < .001), unplanned cardiac reoperation (HR = 2.1 [1.0-4.4], P = .05), and prolonged intensive care unit (ICU) stay >30 days following NP (HR = 2.5 [1.4-4.5], P < .001). Palliative surgery type (shunt, Norwood, band) was not associated with ISM, although aortopulmonary shunt circulation after Norwood was (HR = 5.4 [1.5-19.2] P = .01). Of interest, underlying SV anatomy was not associated with ISM (HR = 1.1 [0.6-2.2], P = .749).

Conclusions:

In our series, ISM following NP occurred in 10% of hospital survivors. As opposed to hospital death, underlying SV anomaly was not associated with ISM. Conversely, several patient factors (prematurity, low weight, and genetic syndromes) and clinical factors (unplanned reoperation and prolonged ICU stay following NP) were associated with ISM. Vigilant outpatient management that is individualized to specific clinical and social needs, taking into account all associated factors, is warranted to improve survival in high-risk patients.
Antiplatelet Effect of Ketorolac in Children After Congenital Cardiac Surgery
Authors: Kim John S. , Kaufman Jon , Patel Sonali S. , Manco-Johnson Marilyn , Di Paola Jorge , da Cruz Eduardo M.
Published: October 2018

Background:

Ketorolac is used for pediatric analgesia after surgery despite its known platelet inhibition via the arachidonic acid (AA) pathway. The degree of platelet inhibitory effect after cardiac surgery is not well characterized. Thromboelastography with platelet mapping (TEG-PM) is emerging as a frequently used test to evaluate platelet inhibition via the AA pathway.

Methods:

Post hoc analysis of a data set collected in a prospective observational cohort study evaluating platelet inhibition in children after congenital heart surgery with cardiopulmonary bypass (CPB). Categorization into two groups: (1) received ketorolac and (2) did not receive ketorolac for analgesia after surgery. The TEG-PM was evaluated at two time points (prior to surgery and 12-48 hours after CPB).

Results:

Fifty-three children were studied; mean age was 6.6 (range: 0.07-16.7) years and 45% (n = 24) were female. Participants were distributed into two groups by ketorolac use, 41 within the ketorolac group and 12 in the no ketorolac group. All 41 participants who received ketorolac had platelet inhibition and 11 (91.7%) of 12 participants who did not receive ketorolac had normal platelet function after surgery ( P < .0001). There was no difference in patient characteristics or clinical data between the two groups.

Conclusions:

Ketorolac use in a cohort of children after congenital cardiac surgery was associated with platelet inhibition via the AA pathway when evaluated by TEG-PM.
Sports Participation Is an Appropriate Expectation for Recreational Athletes Undergoing Shoulder Arthroplasty
Authors: Wang Juntian , Popchak Adam , Giugale Juan , Irrgang James , Lin Albert
Published: October 2018

Background:

Several studies have investigated sports participation in patients who undergo total shoulder arthroplasty (TSA). However, there are limited data in the setting of hemiarthroplasty (HA) and reverse total shoulder arthroplasty (rTSA), particularly regarding the frequency of participation in common sports.

Hypothesis:

The majority of patients who undergo TSA or HA will be able to maintain active lifestyles with high levels of sports participation after their procedure, while patients who undergo rTSA will have lower levels of sports participation.

Study Design:

Case series; Level of evidence, 4.

Methods:

We identified patients who underwent TSA, rTSA, stemmed HA, or humeral head resurfacing (the latter 2 were defined collectively as the HA group) by surgeons within our department since January 2004. We excluded patients who (1) underwent revision arthroplasty, (2) had a history of chronic pain syndrome, (3) experienced septic arthritis of the involved shoulder, and/or (4) were deceased at the time of follow-up. The minimum follow-up from the time of surgery was 2 years. Qualified patients were sent a questionnaire that asked about sports participation and the frequency of participation at the time of follow-up. Frequency was rated as 0, 1 to 3, or 4 to 7 times a week. Sports were defined as lower extremity sport, volleyball, tennis, skiing, bowling, swimming, weight lifting, golf, and other sport.

Results:

Overall, 95% of the TSA group, 40% of the rTSA group, and 76% of the HA group who had participated in at least 1 sport before surgery indicated that they were doing so at the time of follow-up. Among active patients in the TSA and HA groups, the most common sports at the time of follow-up were weight lifting (52%), swimming (36%), and golf (25%). For the 2 active patients in the rTSA group, 1 participated in swimming and hunting and fishing, while the other participated in weight lifting. For the active patients in the TSA and HA groups who were participating in at least 1 of the 3 most common sports, most patients indicated that they were doing so 1 to 3 times a week at the time of completing the questionnaire.

Conclusion:

Patients undergoing shoulder arthroplasty can maintain an active lifestyle with moderate to high frequencies of participation after surgery, particularly regarding weight lifting, swimming, and golf.
Long-term Safety and Efficacy of Sutureless Vitrectomy for Combined Epiretinal and Internal Limiting Membrane Removal
Authors: Ismail Omar M. , Mason John O.
Published: October 2018

Purpose:

The purpose of this case series is to evaluate the long-term visual outcomes of patients undergoing epiretinal membrane (ERM) removal combined with internal limiting membrane (ILM) peeling via sutureless vitrectomy.

Methods:

A retrospective review was conducted of 45 patients (45 eyes) with ERMs treated with 25-gauge pars plana vitrectomy (PPV) from 2010 to 2011. Data assessed included baseline characteristics, preoperative and postoperative best-corrected visual acuity (BCVA), ERM recurrence rate during follow-up, and complications arising during follow-up.

Results:

PPV resulted in a statistically significant improvement in BCVA (20/61 preoperatively, 20/41 1 year postoperatively, and 20/45 at the end of follow-up). Mean duration of follow-up was 66.3 months (range, 26-89). Forty-one of 45 (91%) eyes had improved or stable vision, while 4/45 (8.9%) had worse vision. ERMs recurred in 12/45 eyes (26.7%), of which 1/45 (2.2%) required reoperation. The remaining 11 recurrent ERMs were documented as visually insignificant. Mean time to ERM recurrence was 29.3 months (range, 4-72).

Conclusions:

In one of the longest mean follow-up studies to date, small-gauge PPV for ERM and ILM removal results in statistically significant and stable long-term visual improvement. Despite ILM removal, ERMs did recur in a substantial proportion of patients, though the vast majority were not visually significant.
The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes
Authors: McNamara Caroline J. , Panzarella Tony , Kennedy James A. , Arruda Andrea , Claudio Jaime O. , Daher-Reyes Georgina , Ho Jenny , Siddiq Nancy , Devlin Rebecca , Tsui Hubert , Su Jie , Stockley Tracy , Sukhai Mahadeo , Kanwar Nisha , Chan Steven , Maze Dawn , Schimmer Aaron , Schuh Andre , Sibai Hassan , Viswabandya Auro , Yee Karen , Minden Mark D. , Kamel-Reid Suzanne , Gupta Vikas
Published: October 2018

There is a paucity of data regarding the impact of mutations on outcomes in accelerated-phase (AP) and blast-phase (BP) myeloproliferative neoplasms (MPNs). Moreover, it is unknown whether mutational status affects survival, as seen in chronic-phase MPNs. Therefore, we performed a retrospective analysis of all patients treated at our institution with AP/BP MPNs (N = 122; AP = 14; BP = 108) to comprehensively describe the mutational profile and correlate with clinical outcomes. Targeted sequencing with a 54-gene panel was performed. Forty-four patients were treated with intensive therapy, 27 with nonintensive therapy, and 51 with best supportive care (BSC). The most common mutation was JAK2V617F, occurring in 55% of subjects; CALR was found in 13% of patients and MPL in 6%. Thirty-two (26%) patients were triple negative. Other frequently mutated genes were ASXL1 (30%), TET2 (25%), SRSF2 (22%), RUNX1 (20%), and TP53 (17%). Mutations in 1, 2, 3, and ≥4 genes were seen in 15%, 13%, 25%, and 46% of patients, respectively. There was no difference in survival between patients treated with intensive vs nonintensive therapy, and the benefit of intensive therapy was limited to patients who were able to undergo transplantation. TP53 was the only individual mutation to correlate with shorter overall survival (hazard ratio, 1.89; P = .03). In the multivariate analysis, mutated TP53, ≥4 mutations, low albumin, increased peripheral blood blasts, ≥3 cytogenetic abnormalities, and BSC were associated with shorter survival. In conclusion, mutational data enhance the understanding of patients with AP/BP MPN who are likely to benefit from current therapeutic options.
Absolute proteome quantification of highly purified populations of circulating reticulocytes and mature erythrocytes
Authors: Gautier Emilie-Fleur , Leduc Marjorie , Cochet Sylvie , Bailly Karine , Lacombe Catherine , Mohandas Narla , Guillonneau François , El Nemer Wassim , Mayeux Patrick
Published: October 2018

Reticulocytes produced in the bone marrow undergo maturation in the bloodstream to give rise to erythrocytes. Although the proteome of circulating red cells has been the subject of several reports, the cellular populations used for these studies were never completely devoid of reticulocytes. In our current study, we used highly purified erythrocyte and reticulocyte populations to quantify the absolute expression levels of the proteins in each cell population. Erythrocytes and reticulocytes were purified in a multistep process involving cellulose chromatography, Percoll gradient centrifugation, and fluorescence cell sorting after thiazole orange labeling. Proteins were analyzed by mass spectrometry from whole cells and erythrocyte plasma membrane (ghosts), leading to the identification and quantification of 2077 proteins, including 654 that were reticulocyte-specific. Absolute quantifications of these proteins were made using the mean corpuscular hemoglobin content of the cells as a standard. For each protein, we calculated the percentage loss during the terminal stages of reticulocyte maturation and the percentage of association with the plasma membrane. In addition, we used modified adenosine triphosphate and adenosine diphosphate molecules that enable the transfer of a biotin molecule to the catalytic sites of kinases to isolate active kinases in the erythrocytes and determined the absolute expression of 75 protein kinases and the modification of their expression during reticulocyte maturation. Our findings represent the first absolute quantification of proteins that are specifically expressed in normal erythrocytes with no detectable contamination by reticulocytes. Our findings thus represent a reference database for the future proteomic analysis of pathological erythrocytes.
Visualizing hematopoiesis as a stochastic process
Authors: Xu Jason , Wang Yiwen , Guttorp Peter , Abkowitz Janis L.
Published: October 2018

Stochastic simulation has played an important role in understanding hematopoiesis, but implementing and interpreting mathematical models requires a strong statistical background, often preventing their use by many clinical and translational researchers. Here, we introduce a user-friendly graphical interface with capabilities for visualizing hematopoiesis as a stochastic process, applicable to a variety of mammal systems and experimental designs. We describe the visualization tool and underlying mathematical model, and then use this to simulate serial transplantations in mice, human cord blood cell expansion, and clonal hematopoiesis of indeterminate potential. The outcomes of these virtual experiments challenge previous assumptions and provide examples of the flexible range of hypotheses easily testable via the visualization tool.
The Shiny Balancer - software and imbalance criteria for optimally balanced treatment allocation in small RCTs and cRCTs
Authors: Grischott Thomas
Published: October 2018

Background

In randomised controlled trials with only few randomisation units, treatment allocation may be challenging if balanced distributions of many covariates or baseline outcome measures are desired across all treatment groups. Both traditional approaches, stratified randomisation and allocation by minimisation, have their own limitations. A third method for achieving balance consists of randomly choosing from a preselected list of sufficiently balanced allocations. As with minimisation, this method requires that heterogeneity between treatment groups is measured by specified imbalance metrics. Although certain imbalance measures are more commonly used than others, to the author's knowledge there is no generally accepted “gold standard”, neither for categorical and even less so for continuous variables.

Methods

An intuitive and easily accessible web-based software tool was developed which allows for balancing multiple variables of different types and using various imbalance metrics. Different metrics were compared in a simulation study.

Results

Using simulated data, it could be shown that for categorical variables, χ2-based imbalance measures seem to be viable alternatives to the established “quadratic imbalance” metric. For continuous variables, using the area between the empirical cumulative distribution functions or the largest difference in the three pairs of quartiles is recommended to measure imbalance. Another imbalance metric suggested in the literature for continuous variables, the (symmetrised) Kullback-Leibler divergence, should be used with caution.

Conclusion

The Shiny Balancer offers the possibility to visually explore the balancing properties of several well established or newly suggested imbalance metrics, and its use is particularly advocated in clinical studies with few randomisation units, as it is typically the case in cluster randomised trials.
Comparison of Treatment Recommendations by Molecular Tumor Boards Worldwide
Authors: Rieke Damian T. , Lamping Mario , Schuh Marissa , Le Tourneau Christophe , Basté Neus , Burkard Mark E. , Metzeler Klaus H. , Leyvraz Serge , Keilholz Ulrich
Published: October 2018

Purpose

Precision oncology holds the promise of improving patient outcome. It is based on the idea that the testing of genomic biomarkers can lead to the recommendation of a treatment option tailored to the specific patient. To derive treatment recommendations from molecular profiles, interdisciplinary molecular tumor boards (MTBs) have been established recently in many academic institutions. The recommendation process in MTBs, however, has not been well defined, which limits applicability to larger clinical trials and patient populations.

Methods

We created four fictional patients on the basis of recent real cases with genomic information on mutations, fusions, copy numbers, and gene expression. We identified 29 tumor boards from nine countries worldwide and asked them to provide treatment recommendations for the sample patients. In addition, a questionnaire regarding the setup and methods used by MTBs was circulated.

Results

Five MTBs from four countries provided treatment recommendations and answered the questionnaire. For one patient, three tumor board treatment recommendations were identical, and two tumor boards had identical treatment strategies for the other three patients. There was heterogeneity in the interpretation of tumor and germline aberrations as well as in standards of prioritization.

Conclusion

Differences in the interpretation and recommendation process contribute to heterogeneity in MTB recommendations. Additional comparative analyses of recommendations could help improve rational decision making and lead to standardization.
Thyroid Ultrasound and the Increase in Diagnosis of Low-Risk Thyroid Cancer
Authors: Haymart Megan R , Banerjee Mousumi , Reyes-Gastelum David , Caoili Elaine , Norton Edward C
Published: October 2018

Context

Thyroid cancer incidence increased with the greatest change in adults aged ≥65 years.

Objective

To determine the relationship between area-level use of imaging and thyroid cancer incidence over time.

Design, Setting and Participants

Longitudinal imaging patterns in Medicare patients aged ≥65 years residing in Surveillance, Epidemiology, and End Results (SEER) regions were assessed in relationship to differentiated thyroid cancer diagnosis in patients aged ≥65 years included in SEER-Medicare. Linear mixed-effects modeling was used to determine factors associated with thyroid cancer incidence over time. Multivariable logistic regression was used to determine patient characteristics associated with receipt of thyroid ultrasound as initial imaging.

Main Outcome Measure

Thyroid cancer incidence.

Results

Between 2002 and 2013, thyroid ultrasound use as initial imaging increased (P < 0.001). Controlling for time and demographics, use of thyroid ultrasound was associated with thyroid cancer incidence (P < 0.001). Findings persisted when cohort was restricted to papillary thyroid cancer (P < 0.001), localized papillary thyroid cancer (P = 0.004), and localized papillary thyroid cancer with tumor size ≤1 cm (P = 0.01). Based on our model, from 2003 to 2013, at least 6594 patients aged ≥65 years were diagnosed with thyroid cancer in the United States due to increased use of thyroid ultrasound. Thyroid ultrasound as initial imaging was associated with female sex and comorbidities.

Conclusion

Greater thyroid ultrasound use led to increased diagnosis of low-risk thyroid cancer, emphasizing the need to reduce harms through reduction in inappropriate ultrasound use and adoption of nodule risk stratification tools.