bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint longitudinal and time-to-event models for multilevel hierarchical data
Authors: Brilleman Samuel L , Crowther Michael J , Moreno-Betancur Margarita , Buros Novik Jacqueline , Dunyak James , Al-Huniti Nidal , Fox Robert , Hammerbacher Jeff , Wolfe Rory
Published: October 2018

Joint modelling of longitudinal and time-to-event data has received much attention recently. Increasingly, extensions to standard joint modelling approaches are being proposed to handle complex data structures commonly encountered in applied research. In this paper, we propose a joint model for hierarchical longitudinal and time-to-event data. Our motivating application explores the association between tumor burden and progression-free survival in non-small cell lung cancer patients. We define tumor burden as a function of the sizes of target lesions clustered within a patient. Since a patient may have more than one lesion, and each lesion is tracked over time, the data have a three-level hierarchical structure: repeated measurements taken at time points (level 1) clustered within lesions (level 2) within patients (level 3). We jointly model the lesion-specific longitudinal trajectories and patient-specific risk of death or disease progression by specifying novel association structures that combine information across lower level clusters (e.g. lesions) into patient-level summaries (e.g. tumor burden). We provide user-friendly software for fitting the model under a Bayesian framework. Lastly, we discuss alternative situations in which additional clustering factor(s) occur at a level higher in the hierarchy than the patient-level, since this has implications for the model formulation.
Clinically, what ought we to believe?
Authors: Little John D , Davison Lorraine , Little Robert D
Published: October 2018

Objective:

To question the status of the randomised controlled trial (RCT) in the hierarchy of evidence.

Conclusions:

The RCT provides important and clinically relevant information, particularly in psychopharmacology. However, and as with other methodologies, RCTs too are flawed and automatic abdication to their conclusions, especially in complex social interventions, is unwise. A clinical example with conflicting and polarising views, each with their evidence base, is described alongside a suggested clinical strategy for resolving differences of opinion.
A Review of School Nurses’ Self-Efficacy in Asthma Care
Authors: McCabe Ellen M. , McDonald Catherine , Connolly Cynthia , Lipman Terri H.
Published: October 2018

Asthma is the most common pediatric chronic respiratory illness and has a significant influence on children’s health, school attendance, and overall school success. Despite the effect of education and training, gaps remain in understanding school nurses’ self-efficacy (SE) in asthma care. The purpose of this integrative literature review is to gain a greater understanding of school nurses’ SE in asthma care. Themes and topics in the current school nursing literature regarding SE in asthma care include the value of continuing education, educational interventions, and the use of resources in clinical practice such as the asthma action plan. This review indicates the importance of developing a greater understanding of the unique features of school nursing, the necessary resources, and the external factors that influence practice. Further research to establish a framework to evaluate how a change in practice may support school nurses’ SE and promote positive student health outcomes is needed.
Assessment of Anticoagulation in Patients Receiving Ultrasound-Assisted Catheter-Directed Thrombolysis for Treatment of Pulmonary Embolism
Authors: St. Pierre Bradley P. , Edwin Stephanie B.
Published: October 2018

Background: Ultrasound-assisted, catheter-directed thrombolysis (USAT) has emerged as a popular treatment option for submassive pulmonary embolism (PE). The optimal strategy for transitioning patients from full-intensity to reduced-intensity heparin during the procedure has yet to be established. Objective: The goal of this study was to evaluate the anticoagulation management in patients receiving catheter-directed thrombolysis with USAT. Methods: A retrospective chart review was conducted of patients who received USAT for the treatment of PE. Institutional review board approval was obtained. The primary objective was to determine the proportion of patients with a therapeutic activated partial thromboplastin time (aPTT) prior to and during tissue-plasminogen activator (tPA) infusion. Secondary outcomes included heparin requirements, the rate of bleeding complications, and the appropriateness of long-term venous thromboembolism management. Results: A therapeutic aPTT value was achieved in 32 patients (54.2%) prior to USAT and 35 patients (59.3%) during tPA infusion. Heparin requirements were reduced from 15.1 ± 4.1 to 12.8 ± 4.2 U/kg/h for patients who achieved a therapeutic aPTT both prior to and during tPA infusion. Bleeding occurred in 34.4% of patients and tended to be minimal (20.3%) or minor (10.9%). The majority of patients were discharged on a direct oral anticoagulant (63%), followed by warfarin (32%) and enoxaparin (5%). Conclusion and Relevance: To our knowledge, this is the first study that has assessed heparin management in the setting of USAT. The results of these data may aid in empirically dose adjusting unfractionated heparin to ensure safe and effective anticoagulation for patients receiving USAT.
Anti-Xa Oral Anticoagulant Plasma Concentration Assay in Real Life: Rivaroxaban and Apixaban Quantification in Emergency With LMWH Calibrator
Authors: Billoir Paul , Barbay Virginie , Joly Luc Marie , Fresel Marielle , Chrétien Marie Hélène , Le Cam Duchez Véronique
Published: October 2018

Background: Oral anti-Xa inhibitors have demonstrated noninferiority to vitamin K antagonists (VKAs) for the prevention of stroke in patients with atrial fibrillation and recurrent venous thromboembolism. They are associated with a decrease in major bleeding. In contrast with VKA, no coagulation monitoring is required. However, in clinical practice, determination of drug concentration is sometimes necessary. Objective: The objective of this study was to evaluate a low-molecular-weight heparin (LMWH) calibrated anti-Xa assay for the quantification of rivaroxaban and apixaban plasma concentration in emergency. Methods: The anti-Xa plasma concentration of rivaroxaban and apixaban were measured in emergency in 210 patients using STA anti-Xa liquid assay. For each plasma concentration <150 ng/mL of rivaroxaban or apixaban, an anti-Xa assay calibrated with LMWH was performed. Results: We demonstrated a significant correlation between LMWH anti-Xa activity and rivaroxaban ( R2 = 0.947) or apixaban ( R2 = 0.959) concentration and a significant correlation between rivaroxaban and apixaban plasma concentration ( R2 = 0.972). A LMWH anti-Xa activity <0.50 IU/mL could exclude a plasma concentration of rivaroxaban and apixaban >30 ng/mL and indicate the feasibility of invasive procedure. Conclusion and Relevance: In the absence of a specific test, LMWH-calibrated anti-Xa assay could be used to determine the presence and evaluate the plasma concentration of oral anti-Xa inhibitors. However, these initial findings require confirmation using other chromogenic calibrated oral anti-Xa assays.
The Role of Family During Older Adults’ Living Transitions: Implications for Helping Professionals and Family Counselors
Authors: Branson J. Scott , Branson Ashley , Pozniak Kathryn , Tookes Juanita , Schmidt Maya
Published: October 2018

Adults aged 65 and over comprise approximately 15% of the U.S. population, yet research regarding their experiences during later life transitions remains relatively scant. Our aim in conducting this qualitative study was to better understand relational, developmental, and family life cycle factors that older adults identify as impacting their perceptions of aging and wellness in the context of transitioning into assisted living facilities. In-depth interviews with six participants revealed that attachment across the life span and historic parent–child relationships substantially impacted participants’ perceptions and experiences during later life transitions. These findings support the importance of systemic counseling interventions targeted toward strengthening parent–child relationships across the life span. We conclude with implications for systemic counselors.
“Getting Attention” Creating and Presenting the Visible, Online, Researcher Self
Authors: Cheek Julianne , Øby Elise
Published: October 2018

Using the idea of a digitally based, constructed, and virtual researcher self, we explore ways in which social media, social network sites, and social networking present researcher self(ves) and research product(s) to a range of interested others. We argue that in a climate where visibility of, and attention for, both research and researchers is paramount, we are seeing the resilience and morphing of metrics and all they represent into new and different forms driven by possibilities afforded by social media and social networking. This poses new forms of old problems for qualitative inquiry and qualitative inquirers. However, at the same time, used with care, social media and social networking may open up possibilities for qualitative research to be seen and heard, and better reach those for whom our research is of interest and use. Central questions underpinning the discussion are: How can we use, rather than be used by, the possibilities afforded to our research and researcher selves by social media and social networking? If we cannot always control how our researcher self is presented in social media and social networking sites, how might we resist the researcher self being assembled for us by others such as by their use of altmetrics? Crucially, how can we make sure that qualitative inquiry and expertise is the focus, rather than the gaining of attention, thus avoiding the proliferation of a type of Kardashian qualitative inquiry–related trendsetter and opinion maker based more on ability to gain attention than expertise in qualitative inquiry.
Coming Out (as a Poststructuralist): A Rant
Authors: Teman Eric D. , Lahman Maria K. E.
Published: October 2018

The authors, within the context of the first author Eric’s experiences, explore the politics of a hostile, academically violent pretenure environment as a poststructuralist scholar within a framework of cultural humility. Within this essay, we illuminate issues Eric experienced only after the idea of early tenure was presented by his dean. Most faculty were supportive of Eric and his research; a few were not. We examine issues of prejudice in scholarly works traditionally left unexplored. We wonder what is lost when one way of knowing is privileged over others and advocate for methodological humility. We question the depth of others’ approaches to research when their philosophical stances are unclear and uninterrogated. We challenge researchers to understand and accommodate research approaches which differ from more “received” approaches. We challenge ourselves and qualitative colleagues to assist in the process of respecting and advocating for aesthetic qualitative representations by including them in comprehensive literature reviews. We encourage all scholars to be thoughtful, reflexive, and respectful with colleagues and themselves in their research pursuits.
Ocular flutter as presenting manifestation of pediatric MOG antibody–associated demyelination: A case report
Authors: Breza Marianthi , Smyrni Nikoletta , Koutsis Georgios , Anagnostou Evangelos , Tzartos John , Velonakis Georgios , Kokkinis Constantinos , Kilindireas Constantinos , Papavasiliou Antigone , Kotsalis Charalambos
Published: October 2018

A 13-year-old girl presented with a 5-day history of oscillopsia. On examination, ocular flutter and mild cerebellar signs were found. Brain magnetic resonance imaging (MRI) revealed four periventricular and subcortical non-enhancing lesions. Cerebrospinal fluid (CSF) oligoclonal bands were negative. Neuroblastoma or other malignancies were not found. She responded well to a corticosteroid–intravenous immunoglobulin (IVIG) combination and remained symptom-free for 3 years until presenting again with isolated ocular flutter. Brain MRI at this time remained atypical for classic multiple sclerosis (MS) with a predominance of juxtacortical demyelinating lesions. CSF was positive for oligoclonal bands. Serum myelin oligodendrocyte glycoprotein (MOG) antibodies were present. Ocular flutter can be the presenting feature of MOG antibody–associated pediatric demyelination.
Paediatric MOG antibody–associated ADEM with complex movement disorder: A case report
Authors: Sa Mario , Thornton Rachel , Chong WK Kling , Kaliakatsos Marios , Hacohen Yael
Published: October 2018

Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are a well-recognized cause of acquired demyelinating syndromes in both adult and children. Despite basal ganglia involvement on imaging, movement disorder is not a cardinal feature. We describe a 2-year-9-month-old girl who presented with severe encephalopathy with aphasia, seizures and a complex movement disorder with dystonic posturing and tonic eye deviation. Neuroimaging revealed subtle asymmetrical predominantly white matter signal changes. MOG-Abs were positive in the serum. Other known pathogenic autoantibodies including N-methyl-D-aspartate receptor antibodies (NMDAR-Abs) were negative. The patient made a complete recovery following 2-week corticosteroid treatment. This case highlights the need for MOG-Ab testing in children with suspected autoimmune encephalopathies.
Ethnic diversity matters: Putting implicit associations between weapons and ethnicity in context
Authors: Sadler Melody , Devos Thierry
Published: October 2018

Weapons are implicitly associated with Black Americans. We examined the extent to which this implicit stereotype fluctuates as a function of the ethnic diversity of contexts. Across 351 U.S. metropolitan areas, we tested whether three distinct indicators of ethnic diversity predicted implicit associations between the concept of “weapons” (vs. “harmless objects”) and Black Americans vs. White Americans. As predicted, implicit Black–weapon stereotypes were weaker in areas characterized by the presence of multiple ethnic groups (variety) and greater dispersion of ethnic groups at the neighborhood level (integration). Additionally, the negative association between integration and implicit stereotypes was strongest when minority representation was low compared to high. Considering multiple dimensions of ethnic diversity proved useful to document reliable relations between implicit associations and characteristics of local contexts.
‘I hope you get normal again’: an explorative study on how delirious octogenarian patients experience their interactions with healthcare professionals and relatives after aortic valve therapy
Authors: Instenes Irene , Fridlund Bengt , Amofah Hege A , Ranhoff Anette H , Eide Leslie SP , Norekvål Tone M
Published: October 2018

Background:

Delirium affects nearly half of octogenarian patients after aortic valve replacement, resulting in impaired cognition, reduced awareness and hallucinations. Although healthcare professionals and relatives are often present during episodes, the nature of interactions with them is scarcely studied, and little is known about their long-term experiences.

Purpose:

The purpose of this study was to explore and describe how octogenarian patients with post-aortic valve replacement delirium experience interactions with healthcare professionals and relatives within the first year and four years later.

Method:

An explorative design with qualitative content analysis was used. Delirium was assessed for five consecutive days after aortic valve replacement using the Confusion Assessment Method. Delirious patients ( n=10) were interviewed 6–12 months post-discharge and four years later ( n=5). We used an inductive approach to identify themes in transcribed interviews.

Findings:

An overarching theme emerged: ‘ Healthcare professionals’ and relatives’ responses made a considerable impact on the delirium experience postoperatively and in a long-term’. Three sub-themes described the patients’ experiences: ‘ the need for close supportive care’, ‘ disrespectful behaviour created a barrier’ and ‘ insensitive comments made lasting impressions’. Having healthcare professionals and relatives nearby made the patients feel secure, while lack of attention elevated patients’ emotional distress. Four years later, patients clearly recalled negative comments and unsupportive actions in their delirious state.

Conclusions:

Healthcare professionals and relatives have an essential role in the aortic valve replacement recovery process. Inconsiderate behaviour directed at older patients in delirium elevates distress and has long-term implications. Supportive care focused on maintaining the patients’ dignity and integrity is vital.
‘We call this “play”, however…’: Navigating ‘play anxiety’ in early childhood education and care markets
Authors: Drew Christopher
Published: October 2018

Neoliberal rationalities predicated on consumer choice and market forces have increasingly positioned parents as consumers in early childhood and care markets. In this context, providers jostle to attract clientele by providing pathways through and around a milieu of parental anxieties and ambitions for their children. This article examines a chief marketing document – the early childhood education and care provider’s website – and reflects on the ways providers address parental ‘play anxiety’ in marketised times. It finds that differing and even contradictory discursive ideals about children’s risky, risk averse and guided play move in and out of the texts in ways that work to appeal to parents’ anxieties and desires. The emergence of a mosaic of differing discourses of play in marking texts highlights the complexities and contradictions that come with early childhood education and care provision, parenting and growing up in marketised neoliberal times.
Physical and performance characteristics of nonwoven aviation wipers composed of various staple fibers including raw cotton
Authors: Hron Rebecca J , Hinchliffe Doug J , Cintrón Michael S , Von Hoven Terri , Madison Crista A , Reynolds Michael , Condon Brian D
Published: October 2018

Several nonwoven materials were evaluated as candidates for wipe fabrics intended for sensitive applications, namely aviation maintenance. Wipes designed for this purpose must conform to specific guidelines delineated by the appropriate governing bodies. Fabric selections included both synthetic and natural staple fibers such as polyester, Lyocell and raw cotton varieties. A thorough evaluation of extractable material in an array of solvents revealed that cotton-based nonwovens as well as Lyocell have some of the lowest percentages of leachable solids. The resistance of these fabrics to abrasion and the damage incurred by them was also studied. Environmental scanning electron microscopy taken before and after the linting procedure showed that the greige cotton sample demonstrated some of the least damage. Fourier-transform infrared spectroscopy examinations of hexane extracts confirmed the absence of any silicone grease contamination on the wipes materials. Standardized tensile testing indicated that the cotton samples, especially mechanically cleaned greige cotton, have robust tensile properties that are important characteristics for wiping materials. These results indicate that cotton nonwovens, particularly greige cotton, are promising candidates for the development of future aviation and other wipes materials.
Geospatial Mapping of Late-Life Couplehood: Dimensions of Joint Participation
Authors: Heatwole Shank Kendra S. , Presgraves Echo
Published: October 2018

For older adults aging in place, community mobility affects a constellation of interconnected occupations and can become a problematic aspect of the person–place relationship. The purpose of this research was to examine an older couple’s mutually negotiated change in their community mobility and navigation patterns. Spatial data (using global positioning system [GPS] trackers), maps, activity logs, interviews, and well-being measures were collected longitudinally for both members of a long-married community-dwelling couple. Analyses showed changing patterns of occupational engagement and declining navigation and function over time, as well as three dimensions of joint navigation (intersection of health and abilities, perpetuation of long-term roles through participation, and an orientation toward future potentialities). Findings suggest that joint community navigation is multidimensional and may buffer individual functional losses as well as maximize perception of and performance in meaningful activities. This study also demonstrates the utility of mapping methods to better understand occupation for community-dwelling populations.
Reliability-based covariate analysis for complex systems in heterogeneous environment: Case study of mining equipment
Authors: Moniri-Morad Amin , Pourgol-Mohammad Mohammad , Aghababaei Hamid , Sattarvand Javad
Published: October 2018

Operational heterogeneity and harsh environment lead to major variations in production system performance and safety. Traditional probabilistic model is dealt with time-to-event data analysis, which does not have the capability of quantifying and simulation of these types of complexities. This research proposes an integrated methodology for analyzing the impact of dominant explanatory variables on the complex system reliability. A flexible parametric proportional hazards model is developed by focusing on standard parametric Cox regression model for reliability evaluation in complex systems. To achieve this, natural cubic splines are utilized to create a smooth and flexible baseline hazards function where the standard parametric distribution functions do not fit into the failure data set. A real case study is considered to evaluate the reliability for multi-component mechanical systems such as mining equipment. Different operational and environmental explanatory variables are chosen for the analysis process. Research findings revealed that precise estimation of the baseline hazards function is a major part of the reliability evaluation in heterogeneous environment. It is concluded that an appropriate maintenance strategy potentially mitigate the equipment failure intensity.
Radial polydactyly: putting together evolution, development and clinical anatomy
Authors: Crowley Bríd , Stevenson Susan , Diogo Rui
Published: October 2018

Evolutionary developmental pathology, a new biological field, connects the study of evolution, development and human pathologies. In radial polydactyly, traditional studies have focused mainly on skeletal anomalies. This study examines anatomical and operative records of 54 consecutive cases of radial polydactyly to investigate whether there is a consistent spatial correlation between muscles, tendons and bones and whether this reflects a link between the mechanisms that generate these structures. The data are explored in the context of two current models of limb development: the modularity and topology models. Autopod (hand) tendons and muscles are more predictable in terms of insertion site, supporting both topology and modularity models. Zeugopod (forearm) tendons are less predictable. Neither model universally predicts the anatomy in radial polydactyly. These observations provide evidence for the complexity of anatomy in radial polydactyly and the difficulty in predicting operative findings based on the level of skeletal duplication alone.
Waste water treatment with adsorptions by mushroom compost
Authors: Czikkely Márton , Oláh Judit , Lakner Zoltán , Fogarassy Csaba , Popp József
Published: October 2018

High concentrations of heavy metals (up to the pollution level) can disturb the normal ecosystems of natural rivers. There are some methods for treating heavy metals in waste waters. Heavy metal treatments save the ecosystem and clean drinking water. We determined a new adsorption method for heavy metals using a special mushroom compost, which shows the adsorption capacity of this biomass. The laboratory methods were the preparation of stock solutions from heavy metals, the adsorptions of heavy metals by special mushroom compost with a new technique (shaking method), the degradation of samples and analytical control measurements by inductively coupled plasma mass spectrometry. The results show the success of the new adsorption method. The heavy metal adsorption capacity of this mushroom compost seems to be useful on waste water treatment plants because waste water contains heavy metal ions above the limit concentrations. The new absorption technology solution also includes a special economic analysis that examines material flows. In the sustainable economic analysis, as the circular economy focuses on material and energy circularity combined with natural resources (circular economic value (CEV)), the key question is how to make the systems currently operating in a linear form circular. The difference between CEV%BAU(mod) = 45.5% and CEV%Scen(mod) = 87.5% is the amount of material which could be recycled at the end of life cycle of the product, which is the same as the primary raw material, and so mushroom compost is a completely recyclable material.
Elevated MicroRNA-181a-5p Contributes to Trophoblast Dysfunction and Preeclampsia
Authors: Huang Xiaohao , Wu Lan , Zhang Guoying , Tang Ranran , Zhou Xue
Published: October 2018

Objective:

It has been demonstrated that preeclampsia is associated with alterations in placental microRNA expression. Previous reports have shown that hsa-miR-181a-5p is overexpressed in human preeclamptic placenta compared with normotensive placenta. The purpose of this study was to explore whether upregulated hsa-miR-181a-5p expression is involved in the ontogenesis of preeclampsia.

Methods:

Twenty preeclamptic placentas and 20 normotensive placentas were obtained from nulliparous women by cesarean section. Expression of hsa-miR-181a-5p in placenta tissues and human trophoblast cell lines was analyzed by reverse transcription polymerase chain reaction. The trophoblast cell lines (HTR-8/SVneo and JAR) were transfected with specific oligonucleotides to upregulate miR-181a-5p expression. The effect of miR-181a-5p expression on proliferation, cell cycle, apoptosis, and invasion in HTR-8/SVneo and JAR cells was then investigated.

Result:

It was demonstrated that hsa-miR-181a-5p expression was upregulated in preeclamptic placentas and that it may trigger antiproliferation and inhibition of cell cycle progression, induce apoptosis, and suppress invasion in HTR-8/SVneo and JAR cells.

Conclusion:

Anomalously upregulated hsa-miR-181a-5p expression could contribute to trophoblast dysfunction and may be a crucial factor in the pathogenesis of preeclampsia.
Immunology beliefs as a factor in vaccine opposition among complementary and alternative medical providers
Authors: Bean Sandra J , Catania Joseph A
Published: October 2018

Objectives:

Parental pediatric vaccine decisions are influenced by parents’ health provider networks. Complementary and alternative medical providers may be key influences in the networks of those parents who do not vaccinate their children.

Methods:

From March to July 2013, we conducted semi-structured interviews of Oregon complementary and alternative medical providers ( N = 36) in five disciplines likely to treat parents or children, or both, and whose practitioners are known to express opinions about vaccines and vaccination. We interviewed them concerning their immunology beliefs, vaccine positions, and what these providers recommend to their patients concerning vaccines. We conducted face-to-face interviews and analyzed the interview data using thematic analysis methodology.

Results:

This article identifies the range and type of immunological beliefs of complementary and alternative medical providers concerning pediatric vaccine recommendations. From repeated readings of the data, we identified three areas of alternative immunological beliefs among complementary and alternative medical providers (i.e. “natural is best,” “innate intelligence,” and “the fragile immune system”). In addition, complementary and alternative medical providers who embraced mainstream medicine were likely to be vaccine accepters and to mention vaccines as a positive health measure to their patients—these themes were “vaccines prevent illness” and “herd immunity.”

Conclusion:

Complementary and alternative medical providers influence their patients’ vaccination decisions, particularly urging caution or complete vaccine avoidance, and may be a major influence in states like Oregon with high non-medical exemption rates. Complementary and alternative medical providers come to their anti-vaccine positions largely through post-graduation continuing education courses and seminars. In Oregon, such courses are unregulated and not vetted.
Rate of missed oesophageal cancer at routine endoscopy and survival outcomes: A multicentric cohort study
Authors: Rodríguez de Santiago Enrique , Hernanz Nerea , Marcos-Prieto Héctor Miguel , De-Jorge-Turrión Miguel Ángel , Barreiro-Alonso Eva , Rodríguez-Escaja Carlos , Jiménez-Jurado Andrea , Sierra-Morales María , Pérez-Valle Isabel , Machado-Volpato Nadja , García-Prada María , Núñez-Gómez Laura , Castaño-García Andrés , García García de Paredes Ana , Peñas Beatriz , Vázquez-Sequeiros Enrique , Albillos Agustín
Published: October 2018

Background

Missed oesophageal cancer (MEC) at upper gastrointestinal endoscopy (UGE) is poorly documented.

Objective

The objectives of this study were: (1) to assess the rate, predictors and survival of MEC; (2) to compare MEC and non‐MEC tumours.

Methods

This was a retrospective cohort study conducted at four tertiary centres. Oesophageal cancers (ECs) diagnosed between 2008 and 2015 were included. Patients with a premalignant condition (Barrett, achalasia), prior diagnosis of EC or oesophagogastric junction tumour of gastric origin were excluded. MEC was defined as EC detected within 36 months after negative UGE.

Results

123,395 UGEs were performed during the study period, with 502 ECs being diagnosed (0.4%). A total of 391 ECs were finally included. Overall MEC rate was 6.4% (95% confidence intervals (CI): 4.4–9.3%). The interval between negative and diagnostic UGE was less than 2 years in 84% of the cases. Multivariate analysis showed that a negative endoscopy was associated with proton pump inhibitor (PPI) therapy and less experienced endoscopists. MEC was smaller than non‐MEC at diagnosis (25 versus 40 mm, p = 0.021), more often flat or depressed (p = 0.013) and less frequently diagnosed as metastatic disease (p = 0.013). Overall 2‐year survival rate was similar for MEC (20%) and non‐MEC (24.1%) (p = 0.95).

Conclusions

MEC accounted for 6.4% of all ECs and was associated with poor survival. High‐quality UGE and awareness of MEC may help to reduce its incidence.
Abrasive cytohistology of squamous epithelial lesions
Authors: Burkhardt Arne , Schwarz-Furlan Stephan
Published: October 2018

Objective:

To describe a method to retrieve cellular and tissue elements of oral squamous epithelium obtained by abrasive methods and to conduct investigations by cytohistology.

Method:

We developed a special gelatine pocket suitable for paraffin embedding of sparse material obtained from brush biopsies (BBs). This was subjected to combined evaluation of a cytological (smear) and histological examination of the ‘tissue sections’ – referred as cytohistology. Four diagnostic categories were applied for evaluation. Other special diagnostic methods were also applied in addition to recording dysplasia.

Results:

A total of 51, 755 BBs from suspicious lesions of the oral mucosa (mostly oral potentially malignant disorders – OPMD) were evaluated for the presence of carcinoma or dysplasia; in all, 1.7% were positive, 78.2% were negative for any epithelial atypia, 16.8% atypical and 3.3% inadequate. All BBs also had cytohistological evaluation. A ‘positive’ diagnosis by cytohistology was a reliable indicator of dysplasia or carcinoma, requiring further incisional/excisional biopsy. In the ‘atypical’ category, a variety of lesions were found, about half being dysplasia or carcinoma. This category challenges the clinician for further clinical, therapeutic and/or excisional examination. In ‘negative’ cases with persistence of the lesion, a re-examination in 1-year sequence is recommended.

Conclusion:

Cytohistology of material derived by abrasive methods allows earlier detection of dysplasia/carcinoma. A number of additional oncological and non-oncological findings make this method a valuable non-invasive diagnostic procedure for oral mucosal lesions.
Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia
Authors: Matsuo Hidemasa , Yoshida Kenichi , Fukumura Kazutaka , Nakatani Kana , Noguchi Yuki , Takasaki Saho , Noura Mina , Shiozawa Yusuke , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Okada Ai , Nannya Yasuhito , Takeda June , Ueno Hiroo , Shiba Norio , Yamato Genki , Handa Hiroshi , Ono Yuichiro , Hiramoto Nobuhiro , Ishikawa Takayuki , Usuki Kensuke , Ishiyama Ken , Miyawaki Shuichi , Itonaga Hidehiro , Miyazaki Yasushi , Kawamura Machiko , Yamaguchi Hiroki , Kiyokawa Nobutaka , Tomizawa Daisuke , Taga Takashi , Tawa Akio , Hayashi Yasuhide , Mano Hiroyuki , Miyano Satoru , Kamikubo Yasuhiko , Ogawa Seishi , Adachi Souichi
Published: October 2018

In acute myeloid leukemia (AML), MLL (KMT2A) rearrangements are among the most frequent chromosomal abnormalities; however, knowledge of the genetic landscape of MLL-rearranged AML is limited. In this study, we performed whole-exome sequencing (n = 9) and targeted sequencing (n = 56) of samples from pediatric MLL-rearranged AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. Additionally, we analyzed 105 pediatric t(8;21) AML samples and 30 adult MLL-rearranged AML samples. RNA-sequencing data from 31 patients published in a previous study were also reanalyzed. As a result, we identified 115 mutations in pediatric MLL-rearranged AML patients (2.1 mutations/patient), with mutations in signaling pathway genes being the most frequently detected (60.7%). Mutations in genes associated with epigenetic regulation (21.4%), transcription factors (16.1%), and the cohesin complex (8.9%) were also commonly detected. Novel CCND3 mutations were identified in 5 pediatric MLL-rearranged AML patients (8.9%) and 2 adult MLL-rearranged AML patients (3.3%). Recurrent mutations of CCND1 (n = 3, 2.9%) and CCND2 (n = 8, 7.6%) were found in pediatric t(8;21) AML patients, whereas no CCND3 mutations were found, suggesting that D-type cyclins exhibit a subtype-specific mutation pattern in AML. Treatment of MLL-rearranged AML cell lines with CDK4/6 inhibitors (abemaciclib and palbociclib) blocked G1 to S phase cell-cycle progression and impaired proliferation. Pediatric MLL-MLLT3–rearranged AML patients with coexisting mutations (n = 16) had significantly reduced relapse-free survival and overall survival compared with those without coexisting mutations (n = 9) (P = .048 and .046, respectively). These data provide insights into the genetics of MLL-rearranged AML and suggest therapeutic strategies.
Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial
Authors: Voskaridou Ersi , Ntanasis-Stathopoulos Ioannis , Papaefstathiou Athanasios , Christoulas Dimitrios , Dimopoulou Maria , Repa Konstantina , Papatheodorou Athanasios , Peppa Melpomeni , Terpos Evangelos
Published: October 2018

Denosumab (DNM) is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) that has been licensed for the treatment of different types of osteoporosis. However, the prospective data for the evaluation of DNM efficacy on transfusion-dependent thalassemia (TDT)–induced osteoporosis are rather limited. Thus, we conducted a randomized, placebo-controlled, double-blind, phase 2b clinical trial to evaluate DNM in TDT osteoporosis. Patients were assigned to receive either 60 mg DNM (n = 32) or placebo (n = 31) subcutaneously on day 0 and 180 during a total of 12 months of follow-up. The percentage increase of L1-L4 bone mineral density was higher in the DNM group than the placebo group (5.92% ± 5.25% vs 2.92% ± 5.56%, respectively; P = .043), whereas the advantage of DNM regarding wrist bone mineral density was much higher compared with placebo (−0.26% ± 5.31% vs −3.92% ± 8.71%, respectively; P = .035). No grade 3 or 4 toxicity was observed. DNM reduced pain scores that remained unaltered in the placebo group. DNM showed a significant reduction of soluble RANKL (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase between baseline and the 12th month (P < .01 for all comparisons) without changes in dickkopf-1, sclerostin, and osteocalcin. On the contrary, placebo patients showed an increase in sRANKL, osteoprotegerin, dickkopf-1, sclerostin, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase during the study period (P < .01 for all comparisons). In conclusion, DNM increased lumbar spine and wrist bone mineral density and reduced pain and bone remodeling markers, and thus it is another valuable option for the management of TDT-induced osteoporosis. This trial was registered at www.clinicaltrials.gov as #NCT02559648.
Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo
Authors: Yang Moua , Kholmukhamedov Andaleb , Schulte Marie L. , Cooley Brian C. , Scoggins Na’il O. , Wood Jeremy P. , Cameron Scott J. , Morrell Craig N. , Jobe Shawn M. , Silverstein Roy L.
Published: October 2018

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure.
Optimal timing of surgical antimicrobial prophylaxis in laparoscopic surgery: a before-after study
Authors: Takamatsu Akane , Tagashira Yasuaki , Ishii Kaori , Morita Yasuhiro , Tokuda Yasuharu , Honda Hitoshi
Published: October 2018

Background

The optimal timing of preoperative surgical antimicrobial prophylaxis (SAP) remains uncertain. This study aimed to evaluate the impact of changing the timing of SAP on the incidence of surgical site infection (SSI) in laparoscopic surgery.

Methods

We performed a before-after study from August 2014 through June 2017 to assess the impact of changes in the timing of SAP on the incidence of SSI at a 790-bed tertiary care center in Japan. The intervention was the administration of SAP immediately after the study patients entered the operating room for laparoscopic surgery.

Results

In total, 1397 patients who met the inclusion criteria were analyzed. After the intervention, the median time between the time of SAP completion and the time of surgical incision changed from 8 min to 26 min (p <  0.001), and the number of cases without SAP completion prior to surgical incision decreased (16.8% vs. 1.8%; p <  0.001). However, changes in the overall incidence of SSI did not significantly differ between the pre-intervention and the intervention groups (13.8% vs. 13.2%; p = 0.80).

Conclusions

Although the timing of preoperative SAP improved, the intervention did not have a significant impact on reducing the incidence of SSI in the current study. Besides preoperative SAP, multidisciplinary approaches should be incorporated into projects aimed at comprehensively improving surgical quality to reduce SSI.
Can variation among hypoxic environments explain why different fish species use different hypoxic survival strategies?
Authors: Mandic Milica , Regan Matthew D.
Published: October 2018

In aquatic environments, hypoxia is a multi-dimensional stressor that can vary in O2 level (partial pressure of O2 in water, PwO2), rate of induction and duration. Natural hypoxic environments can therefore be very different from one another. For the many fish species that have evolved to cope with these different hypoxic environments, survival requires adjusting energy supply and demand pathways to maintain energy balance. The literature describes innumerable ways that fishes combine aerobic metabolism, anaerobic metabolism and metabolic rate depression (MRD) to accomplish this, but it is unknown whether the evolutionary paths leading to these different strategies are determined primarily by species' phylogenetic histories, genetic constraint or their native hypoxic environments. We explored this idea by devising a four-quadrant matrix that bins different aquatic hypoxic environments according to their duration and PwO2 characteristics. We then systematically mined the literature for well-studied species native to environments within each quadrant, and, for each of 10 case studies, described the species' total hypoxic response (THR), defined as its hypoxia-induced combination of sustained aerobic metabolism, enhanced anaerobic metabolism and MRD, encompassing also the mechanisms underlying these metabolic modes. Our analysis revealed that fishes use a wide range of THRs, but that distantly related species from environments within the same matrix quadrant have converged on similar THRs. For example, environments of moderately hypoxic PwO2 favoured predominantly aerobic THRs, whereas environments of severely hypoxic PwO2 favoured MRD. Capacity for aerial emergence as well as predation pressure (aquatic and aerial) also contributed to these responses, in addition to other biotic and abiotic factors. Generally, it appears that the particular type of hypoxia experienced by a fish plays a major role in shaping its particular THR.
Thermal Properties of Open-Cage Silsesquioxanes: The Effect of Substituents at the Corners and Opening Moieties
Authors: Yuasa Sota , Sato Yuri , Imoto Hiroaki , Naka Kensuke
Published: October 2018

Incompletely condensed polyhedral oligomeric silsesquioxane (IC-POSS), which has an open-cage structure, exhibits high optical transparency even incorporating 30 wt% of the IC-POSS fillers in a poly(methyl methacrylate) (PMMA) matrix dependent on their substituents. However, real understanding of the substituent-dependent dispersibility of the IC-POSS fillers is unclear. In this work, we studied structure-dependent bulk thermal properties of the IC-POSS derivatives substituting isobutyl, phenyl and cyclohexyl groups at the Si corners and dimethylsilyl, trimethylsilyl, dimethylethylsilyl, dimethylvinylsilyl, dimethylphenylsilyl, and dimethylethylcyclohexyl groups at the opening moieties. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) measurement revealed that both the substituents at the corners and opening moieties significantly affected the thermal properties of the IC-POSS derivatives. We found volcano-type dependence of the phase transition temperature on the molecular weights of the substituents at the opening moieties in all the tested IC-POSS derivatives. The trimethylsilyl groups and the dimethylphenylsilyl groups at the open moieties showed highest and lowest phase transition temperatures, respectively. Especially, the phenyl groups at the opening moieties lead to low melting point and high thermal stability.
Synthesis of Perfluoroalkyl Gelators and Their Selective Gelation Ability for Fluorinated Solvents
Authors: Shimasaki Toshiaki , Ohno Yuki , Tanaka Mao , Amano Masato , Sasaki Yuta , Shibata Hirobumi , Watanabe Motonori , Teramoto Naozumi , Shibata Mitsuhiro
Published: October 2018

Novel perfluoroalkyl gelators without hydrogen bonds–bis(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl) isophthalate (1m), bis(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl) terephthalate (1p), and tris(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl) benzene-1,3,5-tricarboxylate (2)–were synthesized. Their molecular structures were investigated by density functional theory calculations at the B3LYP/cc-pVDZ level. The gelation abilities of 1m, 1p, and 2 were examined and compared to their normal octyl homologues 1m′, 1p′, and 2′. None of the gelators could be gelated in common organic solvents, but gelated well in fluorinated solvents.
Blowing Route towards Advanced Inorganic Foams
Authors: Wang Xue-Bin , Jiang Xiang-Fen , Bando Yoshio
Published: October 2018

In this account, we review a blowing strategy for manufacturing cellular solid materials. Solid foams have been important engineering materials since the early 20th century, and are newly explored for versatile functionalities in recent decades. The blowing route is a practicable technique to yield foams, compatible with scalable industry. With rising 2D materials, the blowing protocol has been applied to synthesizing foams built of 2D materials or nanosheets for the past several years. It is worthy outlining the fundamentals of foaming processes, which include geometry, statics, kinetics, and dynamics in foaming, to study topological constraint, equilibrium configuration, nucleation-growth, and structural evolution, respectively. They are essential for controlling the production towards high-quality foams. Recent progress on foams derived via blowing methods is surveyed, covering traditional foams and newly developed inorganic foams. Advanced foams of boron-carbon-nitrogen systems, e.g. carbon foams, 3D graphene foams, carbon nitride foams, boron nitride foams, doped and hybrid foams, are highlighted and elaborated individually. The relationships between structure, property, and functionality in foam structures are additionally discussed, and the constructive applications of foams are investigated.