bluuebunny/crossref_metadata_2025 huggingface dataset:
Inclusion Is Important . . . But How Do I Include? Examining the Effects of Leader Engagement on Inclusion, Innovation, Job Satisfaction, and Perceived Quality of Care in a Diverse Nonprofit Health Care Organization
Authors: Brimhall Kim C.
Published: February 2019

Nonprofit leaders and managers are recognizing the benefits of creating inclusive organizations in which everyone feels valued and appreciated, yet little is known about how leaders can foster workplace inclusion. This study examined the relationships among leader engagement, inclusion, innovation, job satisfaction, and perceived quality of care in a diverse nonprofit health care organization. Data were collected at three points in 6-month intervals from a U.S. nonprofit hospital. Multilevel path analysis indicated significant direct associations between leader engagement, inclusion, and innovation. Innovation was directly linked to improved job satisfaction and perceived quality of care. Significant indirect effects were found from leader engagement to increased job satisfaction and perceived quality of care through increased climates for inclusion and innovation. Findings suggest that nonprofit leaders who engage others in critical organizational processes can help foster an inclusive climate that leads to increased innovation, employee job satisfaction, and perceived quality of care.
Supersonic nonlinear flutter of cross-ply laminated shallow shells
Authors: Yazdi Ali A
Published: February 2019

The aim of this paper is to investigate the geometrical nonlinear flutter of cross-ply laminated shallow shell with rectangular boundary and strong nonlinearity. The classical laminate plate and piston aerodynamic theories are employed to obtain the governing equation of the systems. The Galerkin method and approximate-analytical homotopy perturbation method are used to predict the flutter boundary of the laminated shallow shell. In this study, the effects of shell geometric dimensions, stacking sequence, and initial deflection on critical flutter pressure are investigated. According to the results, the initial deflection and stacking sequence of the laminated shells can change the nonlinear behavior of shells. The method presented in this study is more accurate than usual perturbation methods in predicting the nondimensional flutter pressure of laminated shallow shell subjected to large initial deflections.
Circulating Microparticles in Children With Sickle Cell Anemia in a Tertiary Center in Upper Egypt
Authors: Zahran Asmaa M. , Elsayh Khalid I. , Saad Khaled , Embaby Mostafa M. , Youssef Mervat A. M. , Abdel-Raheem Yasser F. , Sror Shaban M. , Galal Shereen M. , Hetta Helal F. , Aboul-Khair Mohamed Diab , Alblihed Mohamd A. , Elhoufey Amira
Published: February 2019

Sickle cell disease (SCD) is a genetically inherited hemolytic anemia increasingly appreciated as a chronic inflammatory condition and hypercoagulable state with high thrombotic risk. It is associated with disturbed immune phenotype and function and circulating microparticles (MPs) derived from multiple cell sources. This study was carried out to determine MPs profiles in patients with sickle cell anemia (either on hydroxyurea (HU) therapy or those with no disease-modifying therapy) and to compare these profiles with healthy children. Moreover, our study assesses the potential impact of HU on other aspects of circulating MPs. We performed a cross-sectional study on 30 pediatric patients with SCD divided by treatment into 2 groups (those receiving HU or no therapy) attending Hematology Clinic and 20 age-matched healthy children. The blood samples obtained were analyzed for MPs by flow cytometry. Sickle cell disease group with no therapy showed elevated levels of total, platelet, and erythroid MPs. In contrast, therapy with HU was associated with normalization of MPs. This study provided additional evidence that HU is an effective treatment option in pediatric patients with SCD, as it seems that it decreases the abnormally elevated MPs in those patients.
Natural frequencies of parabolic arches with a single crack on opposite cross-section sides
Authors: Eroglu U , Ruta G , Tufekci E
Published: February 2019

We study natural vibration of elastic parabolic arches, modeled as plane curved beams susceptible to elongation, shear, and bending, exhibiting small concentrated cracks. The crack is simulated by springs between regular chunks, with stiffness evaluated following stress concentration in usual crack opening modes. We evaluate and compare the linear dynamic response of the undamaged and damaged arch in nondimensional form. The governing equations are turned into a system of first-order differential equations that are solved numerically by the so-called matricant. The original contribution of this study lies in highlighting the dependence of the variation of the first natural frequencies on the crack location not only along the axis but also on opposite sides of the cross-section. We obtain the relative variations of the first frequencies in terms of the two crack locations. The result of this direct problem provides information on the possibility to detect such locations, and gives indications on structural monitoring and damage identification.
CDER Experience With Juvenile Animal Studies for CNS Drugs
Authors: Fisher J. Edward , Ravindran Arippa , Elayan Ikram
Published: February 2019

A survey was undertaken to evaluate juvenile animal studies conducted for drug applications reviewed by the Center for Drug Evaluation and Research between 2009 and 2014. Some conclusions about the nonclinical pediatric safety assessment based on studies performed in support of central nervous system–active compounds are presented here. A total of 44 completed studies from 32 New Drug Applications submitted to the Divisions of Psychiatry and Neurology Products were evaluated. Data on animal species and age range used, endpoints evaluated, and outcomes included in labeling were analyzed. Of the drugs evaluated, all but one had studies conducted in rats. In some cases, a second study in a nonrodent species (dog) was also conducted. Indices of growth and development and standard general toxicity parameters were included in all of the studies. Expanded neurohistopathology evaluations, bone mineral density measurements, and reproductive and neurobehavioral functional assessments were also generally carried out. A variety of neurological and neurobehavioral tests were employed. In the majority of rat studies, the potential for long-term cognitive impairment was evaluated using a complex water maze. Juvenile animal studies provided safety information considered relevant to drug use in children and that was included in labeling for 78% of the applications surveyed. The most commonly reported findings in labeling were for neurobehavioral effects, including changes in locomotor activity, auditory startle habituation, and learning and memory. Of the studies described in labeling with neurobehavioral effects, 54% found these effects to be persistent and to provide evidence of developmental neurotoxicity.
Multiple-input multiple-output control of diesel combustion using a control-oriented model
Authors: Yamasaki Yudai , Ikemura Ryosuke , Takahashi Motoki , Kaneko Shigehiko , Uemichi Akane
Published: February 2019

In this study, a multiple-input multiple-output feedforward controller for use with multiple-point fuel injection systems is applied to a diesel engine using an original control-oriented model. The target-tracking performance of this multiple-input multiple-output feedforward controller was then tested in terms of how well the controller adjusts the fuel delivery ratios to the pilot injection, pre-injection, main fuel injection, and the main fuel injection timing, and controls the in-cylinder peak pressure and its timing. Control experiments are conducted at different engine outputs and speeds while changing the targets of the in-cylinder peak pressure and its timing. The controller is able to track the varying targets within an acceptable error included in the original model. The calculation time, which is almost double that of a single-input single-output controller, is sufficiently fast to derive the applicable inputs.
The paradoxes of a localised Islamic orthodoxy: Rethinking Tatar traditional Islam in Russia
Authors: Di Puppo Lili
Published: February 2019

The question of the process of developing national or local forms of Islam is often approached through the lens of the domestication of Islam and by emphasising the role of the state or Muslim officials close to the state in this process. In my analysis of the process, undertaken by certain Tatar Muslim representatives in Russia, of developing what I call a localised Islamic orthodoxy, I aim to study shifts in the debate on ‘traditional Islam’ towards a more theological understanding of the term. I examine attempts to develop a local interpretation of Islam that, while based on universal religious fundaments, is not in opposition to Tatar national traditions and a secular modern lifestyle. The representation of an ‘orthodox traditional Islam’ is necessarily paradoxical to the extent that a localised orthodoxy claims to be timeless, ‘natural’ and established but still needs to be defined, learned and taught following decades of Soviet atheist policies. Furthermore, this representation relies on the projection of orthodoxy onto the past in a process in which certain elements of a complex Tatar Muslim identity are made visible and emphasised (in particular, the Hanafi tradition), while others are obscured. By referring to the literature on orthodoxy in the anthropology and sociology of Islam and in Islamic studies, I aim to examine the theological dimension of the process of defining a local Islam that is currently being pursued by certain Tatar Muslim representatives in Russia.
Effects of dementia knowledge and dementia fear on comfort with people having dementia: Implications for dementia-friendly communities
Authors: Ebert Alexandria R , Kulibert Danica , McFadden Susan H
Published: February 2019

Background and objectives

Advocates for dementia-friendly communities emphasize the need for the public to know about the dementias and to experience social comfort with people having dementia. This research tested a conceptual model of influences on social comfort, including two types of dementia knowledge and personal dementia fear.

Research design and methods

Data were collected from 645 Wisconsin residents through an online platform (Qualtrics®) and community outreach efforts. A hierarchical multiple regression was conducted and its results were mapped onto a figure representing the conceptual model of social comfort.

Results

Greater personhood-based knowledge (based on observations of the capabilities and perspectives of persons with dementia) and less personal dementia fear significantly predicted higher levels of social comfort, while biomedical knowledge did not. Although more personhood-based knowledge improved overall comfort regardless of the level of biomedical knowledge, people with higher levels of biomedical knowledge benefitted the most from having personhood-based knowledge.

Discussion and implications

These findings suggest that activities that promote personhood-based knowledge may enhance social comfort. These activities may be most effective for individuals who already have a high level of biomedical knowledge about people with dementia. Community members and professionals ought to strike a balance between biomedical knowledge and personhood-based knowledge, as the two together may be associated with higher levels of social comfort. This could benefit the promotion of dementia-friendly community initiatives.
Laparoendoscopic Transgastric Resection of Prepyloric Gastrointestinal Stromal Tumor
Authors: Mahajan Nandita Nettu , Singh Nagpal Sajan Jiv , Wong Kee Song Louis M. , Blackmon Shanda H.
Published: February 2019

This case report describes an 83-year-old woman with multiple comorbidities who presented with melena and coffee-ground emesis with diagnostic studies evident for a large prepyloric gastrointestinal stromal tumor. She underwent combined laparoendoscopic transgastric resection surgery for the tumor, performed by a team of gastroenterologist and thoracic surgeon with a successful outcome. The case and videos in this report provide a descriptive demonstration of the steps leading up to the surgical intervention followed by a step-by-step illustration of the combined surgical technique, thus highlighting the importance of multidisciplinary approach for optimal treatment of prepyloric gastrointestinal stromal tumor.
Automatic three-dimensional-scanned garment fitting based on virtual tailoring and geometric sewing
Authors: Duan Li , Yueqi Zhong , Ge Wu , Pengpeng Hu
Published: February 2019

In this article, we presented a new automatic three-dimensional-scanned garment fitting method for A-Pose-scanned human models. Both the garment and the human body were decomposed based on feature lines defined by various landmarks. The patches of the three-dimensional garment were automatically positioned around the human model by setting up the correspondence via feature matching. Virtual sewing was engaged to obtain the final results of virtual dressing. The penetration between cloth model and human model was solved by a geometrical method constrained by Laplacian-based deformation. The experimental results indicated that the proposed method was an efficient way for redressing various garments onto various human models while maintaining the original geometrical features of garments.
The endovascular repair of blunt traumatic thoracic aortic injury in Asia: A systematic review and meta-analysis
Authors: Ho Xin Nee , Wee Ian JY , Syn Nicholas , Harrison Michael , Wilson Lauren , Choong Andrew MTL
Published: February 2019

Introduction

Blunt traumatic thoracic aortic injury, the second leading cause of death from trauma, poses unique challenges in its management. However, there has not yet been a corresponding consolidated series of outcomes reported in Asia, which this systematic review aims to address.

Method

This review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Searches were performed on MEDLINE, EMBASE, Google Scholar, and Cochrane Database for studies performed in Asia reporting the endovascular management of blunt traumatic thoracic aortic injury. Risk of bias was assessed using the Newcastle-Ottawa scale. Meta-analyses of pooled proportions were performed using the metaprop command in STATA. This review has been prospectively registered in PROSPERO (CRD42018083773).

Results

Sixteen retrospective cohort studies were included, reporting a total of 238 patients. The pooled Injury Severity Score was 32.5 (95%CI 27.8–37.1). The pooled mean time to operation from diagnosis was 39.2 hours (95%CI 24.6–53.8 hours), and operation time was 100 min (95%CI 63.5–136.5 min). The pooled rate of procedural conversion from endovascular repair to open surgery was 0.17% (95%CI 0–3.7%), and the proportion of left subclavian artery coverage was 55% (95%CI 37–72%). The pooled prevalence of intra-operative all-cause and aortic-related mortality was 0.72% (95%CI 0–4.9%) and 0.27% (95%CI 0–3.8%), respectively. The pooled prevalence of 30-day all-cause and aortic-related mortality was 2.2% (95%CI 0.16–5.6%) and 2.1% (95%CI 0–3.7%), respectively. In terms of 30-day complication, the pooled prevalence rates of type 1 endoleak, endograft complications, vascular access injury, strokes, and aortic re-rupture were 1.2%, 0.34%, 0.14%, 0.02%, and 0.01%, respectively. There were no cases of types II and III endoleak, and renal failure.

Conclusion

Short- to mid-term results for thoracic endovascular aortic repair for blunt traumatic thoracic aortic injury in Asia are encouraging. However, there is a distinct disparity in reporting across Asia. We propose a prospective database for outcome reporting post thoracic endovascular aortic repair in this patient population, and ongoing follow up to assess long-term efficacy of this treatment strategy.
The multidimensionality of conflict in supervisory boards in education in the Netherlands
Authors: Heemskerk Klaas
Published: February 2019

This article aims to clarify the effects of conflicts on the task performance of supervisory boards in education. Management studies on conflicts on corporate boards sometimes find a positive effect and sometimes a negative effect on the performance of boards. These mixed findings are considered a result of the triggering of harmful personal conflicts through disagreements about process and content within boards. In order to gain more insight into the complex ways in which conflicts influence the effectiveness of supervisory boards in education, a multidimensional operationalisation of conflict has been designed, in which three different types of conflict – task, process and relationship conflict – are distinguished. Chairs of the executive boards of schools in the Netherlands (N = 300) were questioned via a survey on various conflict dimensions and their supervisory board’s task performance. The results of hierarchical regression analyses underscore the need for a multidimensional approach to conflicts on supervisory boards in education. Task conflict has a positive effect and relationship conflict a negative effect, while process conflict seems to have no significant effect on supervisory board effectiveness. Furthermore, task conflicts have a mitigating, rather than a triggering, effect on relationship conflicts. Supervisory boards in education should therefore not avoid substantive discussions on the differences of opinion among their members to be more effective.
“On Cloud Nine”: Positive memories in American Presidential Speeches (1945–2017)
Authors: Adams Tracy , Vinitzky-Seroussi Vered
Published: February 2019

In light of a long chain of horrific tragedies and catastrophes made by both nature and man, the current focus of memory studies on difficult pasts and shameful moments, and the expectation of political leaders to provide comfort and inspiration to their public, this article asks, ‘Is commemoration with joy possible?’ Based on an analysis of 860 American presidential public speeches, this article unpacks the category of positive memories by differentiating between memories of pride, joy, and benignity. It then analyzes the various sources, appearances, and frequency of such memories in ceremonial rhetoric. The article concludes by showing that while positive memories are still a minority they are significantly on the rise. Moreover, while party affiliation matters and effects the choices made by American Presidents, they all pay a unified homage to their predecessors, hinting at future legacy considerations that are untainted by politics.
The joyful power of activist memory: The radiant image of the Commune in the Invisible Committee’s writings
Authors: Fevry Sébastien
Published: February 2019

This article seeks to understand the emotional dynamics surrounding the image of the Paris Commune in connection with its mobilization through contemporary movements of struggle sharing, as their common point, a rejection of neo-liberal capitalism. More precisely, this will involve examining how the affect of joy – understood in Spinoza’s terms as a passion which contributes to increasing the power of action – plays a determining role in the Commune’s discursive deployment in the Invisible Committee’s writings.
Postmemories of joy? Children of Holocaust survivors and alternative family memories
Authors: Wolf Diane L
Published: February 2019

Substantial research in multiple disciplines on Jewish Holocaust survivors and their postwar offspring has been dominated by the discourse of trauma, focusing on the intergenerational transmission of trauma. Based on the narratives of 35 children of Holocaust survivors in the United States, my research counters and nuances this over-determined “paradigm of trauma” by illuminating their more diverse cache of family memories. Some parents transmitted their Holocaust experiences in lively and colorful ways,as an exciting adventure, as a fairy tale, or as a humorous story. The narratives suggest that for these children of survivors, the postmemories of their parents’ history and trauma are embedded in other positive family memories, including the way in which the stories were told. Thus, postmemories of trauma do not necessarily elide or dominate other more positive family memories, including memories of joy
MSA forward: Memory studies moving onward and upward
Authors: Teichler Hanna , Vince Rebekah
Published: February 2019

This article serves as both an état présent of emerging scholarship in the interdisiplinary field of Memory Studies and a conference report following the first MSA Forward interactive workshop which preceded the second annual conference of the Memory Studies Association (MSA) in December 2017. MSA Forward is the postgraduate arm of the Memory Studies Association and offers a platform for exchanging ideas amongst a cohort of emerging scholars engaging with recent developments in Memory Studies and interacting with key academics in the field. The idea of engagement, with its political undertone, draws attention to the political valence and ethical sensitivity of emerging research as evidenced in this article, which contends that if Memory Studies is to be moving forwards as well as looking back, then it is important for emerging scholars as well as established academics to be at the forefront of the field.
Can Threat Increase Support for Liberalism? New Insights Into the Relationship Between Threat and Political Attitudes
Authors: Eadeh Fade R. , Chang Katharine K.
Published: February 2019

The extant literature demonstrates that exposure to threat almost always increases support for political conservatism. But can threat increase the support for political liberalism? The current article provides evidence that threat can increase the aspects of political liberalism. Across three experiments, we find that experimentally manipulated threats to health-care access (Experiment 1, N = 558), pollution (Experiment 2, N = 184), and corporate misconduct (Experiment 3, N = 225) produced increased support for components of liberalism. These findings fill a notable gap in the literature, broadening larger theoretical discussions of threat as a psychological construct and current understandings of experimentally manipulated attitudinal change.
Managing congenital hypogonadotrophic hypogonadism: a contemporary approach directed at optimizing fertility and long-term outcomes in males
Authors: Swee Du Soon , Quinton Richard
Published: February 2019

Hormonal induction of spermatogenesis offers men with azoospermia due to hypogonadotrophic hypogonadism (HH) the promising prospect of fertility restoration. However, an important exception is the subset of individuals affected by congenital hypogonadotrophic hypogonadism (CHH), also known as Kallmann syndrome if associated with anosmia, who often display dismal responses to fertility induction, despite prolonged therapy. This primarily stems from the loss of minipuberty, which is a crucial phase of testicular maturation in early life that has a far-reaching impact on eventual spermatogenic capacity. Further exacerbating the compromised reproductive health is the failure to initiate timely pubertal induction in many CHH patients, resulting in suboptimal genital and psychosexual development. In this paper, the clinical implications and management of male HH across the lifespan is comprehensively reviewed, with a special focus on novel strategies that have the potential to modify disease severity and maximize fertility potential in CHH by addressing the inadequacies of conventional approaches.
Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry
Authors: Kotseva Kornelia , De Backer Guy , De Bacquer Dirk , Rydén Lars , Hoes Arno , Grobbee Diederick , Maggioni Aldo , Marques-Vidal Pedro , Jennings Catriona , Abreu Ana , Aguiar Carlos , Badariene Jolita , Bruthans Jan , Castro Conde Almudena , Cifkova Renata , Crowley Jim , Davletov Kairat , Deckers Jaap , De Smedt Delphine , De Sutter Johan , Dilic Mirza , Dolzhenko Marina , Dzerve Vilnis , Erglis Andrejs , Fras Zlatko , Gaita Dan , Gotcheva Nina , Heuschmann Peter , Hasan-Ali Hosam , Jankowski Piotr , Lalic Nebojsa , Lehto Seppo , Lovic Dragan , Mancas Silvia , Mellbin Linda , Milicic Davor , Mirrakhimov Erkin , Oganov Rafael , Pogosova Nana , Reiner Zeljko , Stöerk Stefan , Tokgözoğlu Lâle , Tsioufis Costas , Vulic Dusko , Wood David ,   on behalf of the EUROASPIRE Investigators*
Published: February 2019

Aims

The aim of this study was to determine whether the Joint European Societies guidelines on secondary cardiovascular prevention are followed in everyday practice.

Design

A cross-sectional ESC-EORP survey (EUROASPIRE V) at 131 centres in 81 regions in 27 countries.

Methods

Patients (<80 years old) with verified coronary artery events or interventions were interviewed and examined ≥6 months later.

Results

A total of 8261 patients (females 26%) were interviewed. Nineteen per cent smoked and 55% of them were persistent smokers, 38% were obese (body mass index ≥30 kg/m2), 59% were centrally obese (waist circumference: men ≥102 cm; women ≥88 cm) while 66% were physically active <30 min 5 times/week. Forty-two per cent had a blood pressure ≥140/90 mmHg (≥140/85 if diabetic), 71% had low-density lipoprotein cholesterol ≥1.8 mmol/L (≥70 mg/dL) and 29% reported having diabetes. Cardioprotective medication was: anti-platelets 93%, beta-blockers 81%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75% and statins 80%.

Conclusion

A large majority of coronary patients have unhealthy lifestyles in terms of smoking, diet and sedentary behaviour, which adversely impacts major cardiovascular risk factors. A majority did not achieve their blood pressure, low-density lipoprotein cholesterol and glucose targets. Cardiovascular prevention requires modern preventive cardiology programmes delivered by interdisciplinary teams of healthcare professionals addressing all aspects of lifestyle and risk factor management, in order to reduce the risk of recurrent cardiovascular events.
Differential effect of regadenoson versus dipyridamole on heart rate in patients with left bundle branch block: How does it affect the results of pharmacological nuclear stress testing?
Authors: Assaad Mahmoud , Berry Abeer , Palanisamy Jaishree , Fenner Joseph , Zughaib Marcel
Published: February 2019

Background

Myocardial perfusion imaging (MPI) stress test is performed either using exercise as a stress modality or through the use of pharmacological vasodilator agents in those who cannot exercise. Regadenoson and dipyridamole are some of the most common vasodilator agents used. We aim to study the effect of these agents on the heart rate and the imaging results.

Methods

This was a retrospective study which included 187 patients with left bundle branch block. Patients received either dipyridamole or regadenoson during the myocardial perfusion imaging stress test. Charts were reviewed, and patient characteristics were recorded, as well as baseline heart rate, peak heart rate during stress, and angiographic data if available.

Results

Regadenoson increased peak, absolute and relative heart rates significantly more compared to dipyridamole. The peak heart rate for Regadenoson was 94.1 ± 17.36 and for dipyridamole it was 85.38 ± 16.48 BPM (P < 0.001). The relative and absolute heart rate increase in the regadenoson group were 40.75 ± 23.01% and 26.06 ± 13.44 BPM, respectively. The relative and absolute heart rate increase in the dipyridamole group were 24.61 ± 18.25% and 16.23 ± 10.97 BPM. The frequency of reversible septal defects was similar in both groups (54% for Regadenoson vs. 63% for Dipyridamole; P = 0.24).

Conclusions

There is a statistically significant increase in heart rate with the use of regadenoson for MPI compared to dipyridamole. However, the number of septal perfusion defects was similar between the two groups. The effect of this increase in heart rate, while statistically significant, is likely of no clinical significance.
A rare case of renal collision tumour of oncocytoma and sarcomatoid renal cell carcinoma
Authors: Chang Dwayne , Woods Cliff , Sreeramula Neeraja , Baskaranathan Sriskanthan
Published: February 2019

Level of evidence: 4
Racial and Ethnic Disparities in Provider-Related Barriers to Health Care for Children in California After the ACA
Authors: Alberto Cinthya K. , Kemmick Pintor Jessie , McKenna Ryan M. , Roby Dylan H. , Ortega Alexander N.
Published: February 2019

The aim of this study was to examine disparities in provider-related barriers to health care by race and ethnicity of children in California after the implementation of the Affordable Care Act (ACA). California Health Interview Survey child (0-11 years) survey data from 2014 to 2016 were used to conduct multivariable logistic regressions to estimate the odds of reporting any provider-related barrier, trouble finding a doctor, child’s health insurance not accepted by provider, and child not being accepted as a new patient. Compared with parents of non-Latino white children, parents of non-Latino black, Latino, Asian, and other/multiracial children were not more likely to report experiencing any of the 4 provider-related barrier measures. The associations between children’s race and ethnicity and parents’ reports of provider-related barriers were nonsignificant. Findings demonstrate that there are no significant racial/ethnic differences in provider-related barriers to health care for children in California in the post-ACA era.
Density functional theory study of the stability of the tetrabutylphosphonium and tetrabutylammonium montmorillonites
Authors: Scholtzová Eva , Tunega Daniel
Published: February 2019

The stability of organoclays prepared from smectites and organic cations depends on the type of used cation, among other factors. This study provides a prediction of the structure, stability and dynamic properties of organoclays based on montmorillonite (Mt) intercalated with two types of organic cations – tetrabutylammonium (TBA) and tetrabutylphosphonium (TBP) – using first-principle density functional theory. The results obtained from simulations were also used in the interpretation of the experimental infrared spectrum of the TBP-Mt organoclay. Analysis of interatomic distances showed that weak C–O···H hydrogen bonds were important in the stabilization of both TBA- and TBP-Mt models, with slightly stronger hydrogen bonds for the TBP cation. Calculated intercalation and adsorption reaction energies (ΔEint//ΔEads*/ΔEads**) confirmed that TBP-Mt structures (–72.4//–32.8/–53.8 kJ/mol) were considerably more stable than TBA-Mt structures (–56.7//–22.6/–37.4 kJ/mol). The stronger interactions of the alkyl chains of the TBP cation with Mt basal surfaces in comparison to those of the TBA cation were also correlated with the positions of the calculated bands of the C–H stretching vibrations.
The Immune Checkpoint Kick Start: Optimization of Neoadjuvant Combination Therapy Using Game Theory
Authors: West Jeffrey , Robertson-Tessi Mark , Luddy Kimberly , Park Derek S. , Williamson Drew F.K. , Harmon Cathal , Khong Hung T. , Brown Joel , Anderson Alexander R.A.
Published: February 2019

Purpose

In an upcoming clinical trial at the Moffitt Cancer Center for women with stage 2/3 estrogen receptor–positive breast cancer, treatment with an aromatase inhibitor and a PD-L1 checkpoint inhibitor combination will be investigated to lower a preoperative endocrine prognostic index (PEPI) that correlates with relapse-free survival. PEPI is fundamentally a static index, measured at the end of neoadjuvant therapy before surgery. We have developed a mathematical model of the essential components of the PEPI score to identify successful combination therapy regimens that minimize tumor burden and metastatic potential, on the basis of time-dependent trade-offs in the system.

Methods

We considered two molecular traits, CCR7 and PD-L1, which correlate with treatment response and increased metastatic risk. We used a matrix game model with the four phenotypic strategies to examine the frequency-dependent interactions of cancer cells. This game was embedded in an ecological model of tumor population-growth dynamics. The resulting model predicts evolutionary and ecological dynamics that track with changes in the PEPI score.

Results

We considered various treatment regimens on the basis of combinations of the two therapies with drug holidays. By considering the trade off between tumor burden and metastatic potential, the optimal therapy plan was a 1-month kick start of the immune checkpoint inhibitor followed by 5 months of continuous combination therapy. Relative to a protocol giving both therapeutics together from the start, this delayed regimen resulted in transient suboptimal tumor regression while maintaining a phenotypic constitution that is more amenable to fast tumor regression for the final 5 months of therapy.

Conclusion

The mathematical model provides a useful abstraction of clinical intuition, enabling hypothesis generation and testing of clinical assumptions.
DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma
Authors: Flinn Ian W. , Miller Carole B. , Ardeshna Kirit M. , Tetreault Scott , Assouline Sarit E. , Mayer Jiri , Merli Michele , Lunin Scott D. , Pettitt Andrew R. , Nagy Zoltan , Tournilhac Olivier , Abou-Nassar Karem-Etienne , Crump Michael , Jacobsen Eric D. , de Vos Sven , Kelly Virginia M. , Shi Weiliang , Steelman Lori , Le NgocDiep , Weaver David T. , Lustgarten Stephanie , Wagner-Johnston Nina D. , Zinzani Pier Luigi
Published: February 2019

PURPOSE

Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy.

PATIENTS AND METHODS

Eligible patients had measurable iNHL (FL, SLL, or marginal zone B-cell lymphoma) double refractory to rituximab (monotherapy or in combination) and to either chemotherapy or radioimmunotherapy. All were treated with duvelisib 25 mg orally twice daily in 28-day cycles until progression, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) using the revised International Working Group criteria for malignant lymphoma.

RESULTS

This open-label, global phase II trial enrolled 129 patients (median age, 65 years; median of three prior lines of therapy) with an ORR of 47.3% (SLL, 67.9%; FL, 42.2%; MZL, 38.9%). The estimated median duration of response was 10 months, and the estimated median progression-free survival was 9.5 months. The most frequent any-grade treatment-emergent adverse events (TEAEs) were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Among the 88.4% of patients with at least one grade 3 or greater TEAE, the most common TEAEs were neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%).

CONCLUSION

In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies.
Maternal BMI, Peripheral Deiodinase Activity, and Plasma Glucose: Relationships Between White Women in the HAPO Study
Authors: Haddow James E , Metzger Boyd E , Lambert-Messerlian Geralyn , Eklund Elizabeth , Coustan Donald , Catalano Patrick , Palomaki Glenn E
Published: February 2019

Objectives

Explore the maternal body mass index (BMI) relationship with peripheral deiodinase activity further. Examine associations between deiodinase activity, glucose, and C-peptide. Consider findings in the historical context of related existing literature.

Design

Identify fasting plasma samples and selected demographic, biophysical, and biochemical data from a subset of 600 randomly selected non-Hispanic white women recruited in the Hyperglycemia Adverse Pregnancy Outcomes (HAPO) study, all with glucose tolerance testing [545 samples sufficient to measure TSH, free T4 (fT4), and T3]. Exclude highest and lowest 1% TSH values (535 available for analysis). Assess deiodinase activity by using T3/fT4 ratios. Among women with and without gestational diabetes mellitus (GDM), compare thyroid measurements, C-peptide, and other selected data. Examine relationships independent of GDM status between BMI and thyroid hormones and between thyroid hormones and glucose and C-peptide.

Results

Levels of BMI, T3/fT4 ratio, and T3 were significantly higher among women with GDM (P = 0.01, 0.005, and 0.001, respectively). Irrespective of GDM status, maternal BMI was associated directly with both T3/fT4 ratio (r = 0.40, P < 0.001) and T3 (r = 0.34, P < 0.001) but inversely with fT4 (r = −0.21, P < 0.001). In turn, fasting thyroid hormone levels (most notably T3/fT4 ratio) were directly associated with maternal glucose [z score sum (fasting, 1, 2 hours); r = 0.24, P < 0.001] and with C-peptide [z score sum (fasting, 1 hour); r = 0.27, P < 0.001].

Conclusions

Higher BMI was associated with increased deiodinase activity, consistent with reports from elsewhere. Increased deiodinase activity, in turn, was associated with higher glucose. Deiodinase activity accounts for a small percentage of z score sum glucose.
Inadvertent Traditionalism
Authors: Khazzoom Aziza
Published: February 2019

In Israel, Middle Eastern women are read as more “traditional” than European women. Yet life-story interviews conducted for this article reveal that elderly Polish Jewish women self-present as traditionally feminine—emphasizing home-centeredness, passivity, modesty, self-sacrifice, and delicateness—in ways a matched group of Iraqis do not. The article shows that these presentations are a by-product of how Poles assert Western identity. They claim Westernness by emphasizing continuity between their current behaviors and ideals and those they were taught in upper-class 1930s Europe, including feminine ideals. They see these behaviors as European and are inattentive to potential links with traditionalism. The discussion focuses on this finding in light of arguments that for women classified as Western, being on the “liberated” side of Orientalist contrasts can render gender invisible, enabling reproduction of gender inequality.
Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate
Authors: Wegner Kyle A. , Mehta Vatsal , Johansson Jeanette A. , Mueller Brett R. , Keil Kimberly P. , Abler Lisa L. , Marker Paul C. , Taketo M. Mark , Headon Denis J. , Vezina Chad M.
Published: February 2019

Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription but whether CTNNB1 acts by a similar mechanism in prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR pathway during prostate development. In situ hybridization studies reveal EDAR pathway components including Wnt10b in developing prostate and localize these factors to prostatic bud epithelium where CTNNB1 target genes are co-expressed. We used a genetic approach to ectopically activate CTNNB1 in developing mouse prostate and observed focal increases in Edar and Wnt10b mRNAs. We also used a genetic approach to test the prostatic consequences of activating or inhibiting Edar expression. Edar overexpression does not visibly alter prostatic bud formation or branching morphogenesis, and Edar expression is not necessary for either of these events. However, Edar overexpression is associated with an abnormally thick and collagen-rich stroma in adult mouse prostate. These results support CTNNB1 as a transcriptional activator of Edar and Wnt10b in developing prostate and demonstrate Edar is not only important for ectodermal appendage patterning but also influences collagen organization in adult prostate.
The lineage-specific transcription factor CDX2 navigates dynamic chromatin to control distinct stages of intestine development
Authors: Kumar Namit , Tsai Yu-Hwai , Chen Lei , Zhou Anbo , Banerjee Kushal K. , Saxena Madhurima , Huang Sha , Toke Natalie H. , Xing Jinchuan , Shivdasani Ramesh A. , Spence Jason R. , Verzi Michael P.
Published: February 2019

Lineage-restricted transcription factors, such as the intestine-specifying factor CDX2, often have dual requirements across developmental time. Embryonic loss of CDX2 triggers homeotic transformation of intestinal fate, whereas adult-onset loss compromises crucial physiological functions but preserves intestinal identity. It is unclear how such diverse requirements are executed across the developmental continuum. Using primary and engineered human tissues, mouse genetics, and a multi-omics approach, we demonstrate that divergent CDX2 loss-of-function phenotypes in embryonic versus adult intestines correspond to divergent CDX2 chromatin-binding profiles in embryonic versus adult stages. CDX2 binds and activates distinct target genes in developing versus adult mouse and human intestinal cells. We find that temporal shifts in chromatin accessibility correspond to these context-specific CDX2 activities. Thus, CDX2 is not sufficient to activate a mature intestinal program; rather, CDX2 responds to its environment, targeting stage-specific genes to contribute to either intestinal patterning or mature intestinal function. This study provides insights into the mechanisms through which lineage-specific regulatory factors achieve divergent functions over developmental time.
How does T cell receptor clustering impact on signal transduction?
Authors: Goyette Jesse , Nieves Daniel J. , Ma Yuanqing , Gaus Katharina
Published: February 2019

The essential function of the T cell receptor (TCR) is to translate the engagement of peptides on the major histocompatibility complex (pMHC) into appropriate intracellular signals through the associated cluster of differentiation 3 (CD3) complex. The spatial organization of the TCR–CD3 complex in the membrane is thought to be a key regulatory element of signal transduction, raising the question of how receptor clustering impacts on TCR triggering. How signal transduction at the TCR–CD3 complex encodes the quality and quantity of pMHC molecules is not fully understood. This question can be approached by reconstituting T cell signaling in model and cell membranes and addressed by single-molecule imaging of endogenous proteins in T cells. We highlight such methods and further discuss how TCR clustering could affect pMHC rebinding rates, the local balance between kinase and phosphatase activity and/or the lipid environment to regulate the signal efficiency of the TCR–CD3 complex. We also examine whether clustering could affect the conformation of cytoplasmic CD3 tails through a biophysical mechanism. Taken together, we highlight how the spatial organization of the TCR–CD3 complex – addressed by reconstitution approaches – has emerged as a key regulatory element in signal transduction of this archetypal immune receptor.
Predictive models of subcellular localization of long RNAs
Authors: Zuckerman Binyamin , Ulitsky Igor
Published: February 2019

Export to the cytoplasm is a key regulatory junction for both protein-coding mRNAs and long noncoding RNAs (lncRNAs), and cytoplasmic enrichment varies dramatically both within and between those groups. We used a new computational approach and RNA-seq data from human and mouse cells to quantify the genome-wide association between cytoplasmic/nuclear ratios of both gene groups and various factors, including expression levels, splicing efficiency, gene architecture, chromatin marks, and sequence elements. Splicing efficiency emerged as the main predictive factor, explaining up to a third of the variability in localization. Combination with other features allowed predictive models that could explain up to 45% of the variance for protein-coding genes and up to 34% for lncRNAs. Factors associated with localization were similar between lncRNAs and mRNAs with some important differences. Readily accessible features can thus be used to predict RNA localization.
Comparative evaluation of sensitivity and specificity of immunochromatography kit for the rapid detection of norovirus and rotavirus in Bangladesh
Authors: Shaha Modhusudon , Sifat Sadia Farzana , Mamun Md. Al , Billah Md. Baki , Sharif Nadim , Nobel Nasir Uddin , Parvez Anowar Khasru , Talukder Ali Azam , Nomura Akiko , Ushijima Hiroshi , Dey Shuvra Kanti
Published: February 2019

We report a comprehensive analysis of sensitivity and specificity of immunochromatography kit (IC Kit) for the rapid detection of norovirus and rotavirus in Bangladesh. The IC kit (IP-Noro/Rota) provides highest sensitivity (100%) to both viruses compared to the reference method reverse transcription- polymerase chain reaction (RT- PCR) for diagnosis. Furthermore, the test provides a high specificity of 98.9% and 96.1% to diagnose norovirus and rotavirus, respectively, as well as good agreement with the reference method. We also found high prevalence of rotavirus infection (74%) among Bangladeshi pediatric population, of which most of the patients were less than five years old, suffering from severe dehydration, abdominal pain and vomiting. This study is the first to report the ease and rapid detection of norovirus and rotavirus by IC kits in Bangladesh. Therefore, IP-Noro/Rota kit is recommended for the rapid detection of these viruses in routine diagnosis as well as during outbreaks.
Epidemiology of zoonotic tick-borne diseases in Latin America: Are we just seeing the tip of the iceberg?
Authors: Rodriguez-Morales Alfonso J. , Bonilla-Aldana D. Katterine , Idarraga-Bedoya Samuel E. , Garcia-Bustos Juan J. , Cardona-Ospina Jaime A. , Faccini-Martínez Álvaro A.
Published: February 2019

Ticks are responsible for transmission of multiple bacterial, parasitic and viral diseases. Tick-borne diseases (TBDs) occur particularly in tropical and also subtropical areas. The frequency of these TBDs has been increasing and extending to new territories in a significant way, partly since ticks’ populations are highly favored by prevailing factors such as change in land use patterns, and climate change. Therefore, in order to obtain accurate estimates of mortality, premature mortality, and disability associated about TBDs, more molecular and epidemiological studies in different regions of the world, including Latin America, are required. In the case of this region, there is still a limited number of published studies. In addition, there is recently the emergence and discovering of pathogens not reported previously in this region but present in other areas of the world. In this article we discuss some studies and implications about TBDs in Latin America, most of them, zoonotic and with evolving taxonomical issues.