bluuebunny/crossref_metadata_2025 huggingface dataset:
Transport modes and tourism seasonality in Italy: By air or by road?
Authors: Vergori Anna Serena , Arima Serena
Published: November 2020

From the late 1990s, the European air transport deregulation has led to the increasing use of the plane to reach tourist destinations. This article investigates the impact of tourists’ changed traveling habits on Italy’s seasonal tourism demand pattern. The role of transportation on seasonality, indeed, has been almost neglected in empirical research. We analyze international monthly arrivals by transport modes from 1997 to 2018, and we use the Gini index as a measure of seasonality. The Gini’s decomposition allows us to evaluate the effects of the growth in the use of each transport mode (cars, planes, ships, trains) on seasonality. A beta regression model confirms that an increment in the proportion of tourist arrivals by airplane determines a reduction in Italy’s overall seasonality of international tourism demand. These results might be a starting point for policy makers in developing strategies to counteract seasonality.
Condition evaluation for through and half-through arch bridges considering robustness of suspended deck systems
Authors: Fan Bing-Hui , Su Jia-Zhan , Chen Bao-Chun
Published: November 2020

Through and half-through arch bridges is one of the main bridge types in China, having arch ribs and simple suspended deck systems, which are connected by high-strength wire suspenders. However, due to the lack of robustness, the suspended deck systems of these types of bridges caused progressive collapse after the suspender corrosion damage. In this study, the internal structural factor of progressive collapse induced by suspender failure was revealed by comparison of five cases of suspender failure, and the robustness requirement of the suspended deck systems was proposed as redundancy to avoid transverse beam collapse when two supporting suspenders on both ends were broken at the same time. Meanwhile, a typical rigid-framed tied through concrete-filled steel tube arch bridge was investigated, and structural condition evaluation was carried out based on the Chinese standard (JTG/T H21-2011). It was found that the evaluation results of bridges with different deck systems were unreasonable, as the better the robustness was, the worse the condition of the deck system was rated, which would mislead the bridge maintenance decisions. A robustness-based evaluation method was then proposed by adopting different evaluation method according to the robustness of the suspended deck system, which is determined by qualitative classification or quantitative calculation. In addition, weight-adjusting method considering robustness was introduced in the evaluation process. The result showed that the new method could objectively reflect the condition of the bridge and thus fits the needs of bridge maintenance and management better.
Knowledge, attitudes and practice of self-medication among university students in Portugal: A cross-sectional study
Authors: Alves Regina Ferreira , Precioso José , Becoña Elisardo
Published: November 2020

Aims:

To describe the knowledge, attitudes and practices of self-medication in college students and to analyse the predicting factors for the engagement in that behaviour.

Design:

This is a cross-sectional study involving students ( n = 840) from a Portuguese university, selected through stratified and proportional sampling. Data were collected using a self-administered questionnaire containing, in addition to sociodemographic issues, a scale measuring knowledge about self-medication (α = .488), a scale measuring attitudes towards self-medication (α = .708) and questions about the patterns of self-medication practices (α = .445). Differences between outcomes and sociodemographics were analysed through independent t-tests and ANOVA. A generalised linear model was calculated to determine the predictive variables of self-medication.

Results:

Over half of the respondents ( 54.3%, n = 434) had used some form of self-medication during the preceding year. Students revealed poor knowledge about the referred practice, correctly answering 1.60 ( SD = 0.936) questions in a total of 3, and favourable attitudes towards self-medication ( M = 2.17, SD = 0.950, range 1–5). Attending engineering sciences (β = .718, 95% CI: 1.373–3.069, p < .001), being female (β = .866, 95% CI: 1.700–3.327, p < .001) and having negative attitudes towards self-medication (β = .367, 95% CI: 1.227–1.698, p < .001) predict the adoption of those practices.

Conclusions:

Self-medication is a common practice among university students, the level of self-medication knowledge is low and the low score of the level of attitudes revealed that students tended to have a correct positioning towards self-medication. Therefore, the recommendation to develop campaigns or educational programmes becomes obvious, in order to inform about the adverse effects of the use of non-prescribed medicine.
In vitro comparison of the torsional load transfer of various commercially available stainless-steel wires used for fixed retainers in orthodontics
Authors: Engeler Olivia G , Dalstra Michel , Arnold Dario T , Steineck Markus , Verna Carlalberta
Published: November 2020

Objective:

To assess the torsional load transfer of various commercially available stainless-steel wires used for fixed retainers.

Design:

An in vitro study using a robotic device.

Setting:

Department of Pediatric Oral Health and Orthodontics, University of Basel.

Methods:

A 10° proclination of a maxillary lateral incisor of a 2-2 retainer was simulated with a robotic device. Eight stainless-steel wires with different shapes (round or rectangular), types (plain, braided, coaxial or chain) and dimensions were selected to measure the torsional load transfer at the adjacent central incisor. The influence of annealing was also tested.

Results:

The 0.016 × 0.016 and Bond-A-Braid™ wires (0.02645 × 0.01055-inch, 8-stranded, braided) showed the largest relative torsional load transfer (3.7% and 3.3%, respectively). The two multistranded wires - Triple Flex™ and Respond® - showed the smallest values of 1.0% and 0.7%, respectively. The spiral direction of these two multistranded wires affected the load transfer, the twisting showing larger torsional load transfer than the untwisting one.

Conclusion:

The effective torsional load transfer depends on the dimension, shape and type of a wire. Plain and braided retainers were more predictable in torsional load transfer than multistranded retainers, which may have stored more energy in the area between the composite bonding sites. This may explain the unexpected complications reported in multistranded retainers.
Pre-chamber ignition systems: A methodological proposal to reproduce a reference case in a simplified experimental facility for fundamental studies
Authors: Desantes José M , López J Javier , Novella Ricardo , Antolini Jácson
Published: November 2020

To further understand the processes and phenomena taking place in the pre-chamber (PC) ignition concept, many studies under simplified conditions have been carried out in different experimental facilities (e.g. constant volume chambers and rapid compression machines). However limited information is provided about how the volume, orifice diameter and number of orifices were defined, raising the question whether the results are representative of engine-like conditions or not. This novel study arises from the necessity to determine a methodology to reproduce a reference pre-chamber, preserving as much as possible its jet characteristics. A theoretical development based on the first law of thermodynamics has been performed, and a relationship between the effective flow area, pre-chamber volume and engine speed is proposed as the governing parameter of the mass exchange between chambers. Besides, relaying on the know-how of gas jets, a relationship between the orifice diameter, jet tip penetration and engine speed is suggested as the criterion to preserve the relative jet penetration (respect to the distance from the PC hole to the combustion chamber walls). A numerical validation of these assumptions was carried out using a one-dimensional flow calculator to estimate the thermodynamic properties and mass transfer between chambers, and a one-dimensional spray model to estimate the penetration of the PC combustion products jets. Finally, preserving the ratio between the total area of the PC holes and the product of the PC volume and the engine speed for two pre-chamber geometries, an identical pressure rise rate, in an angular basis, is achieved in both pre-chambers. Furthermore, the same relative jet penetration rate, in an angular basis, can be also achieved, even under different engine speeds, when the ratio between the orifice diameter and the product of the square of the jet free length and the engine speed is preserved.
Beyond crisis: Enacted sense-making among ethnic minority carers of people with dementia in Australia
Authors: Brijnath Bianca , Gilbert Andrew Simon , Kent Mike , Ellis Katie , Browning Colette , Goeman Dianne , Adams Jon , Antoniades Josefine
Published: November 2020

The ‘family crisis’ narrative is frequently used in dementia studies to explain ethnic minority families’ pathways to health and aged care and why there is delayed dementia diagnoses in ethnic minority communities. Such narratives may obscure the family carers’ agency in negotiating services and managing personal, social and structural burdens in the lead up to diagnosis. To illuminate agency, this article describes ethnic minority families’ pathways to a dementia diagnosis using the concept of sense-making. Three case studies were drawn from 56 video interviews with family carers of older adults with dementia from Chinese, Arab and Indian backgrounds. Interviews were conducted across Australia from February to August 2018, then translated, transcribed and thematically analysed. Findings suggest families did not enter into formal care because of a crisis, instead navigating fragmented systems and conflicting advice to obtain a dementia diagnosis and access to relevant care. This experience was driven by sense-making (a search for plausible explanations) that involved family carers interpreting discrepant cues in changes to the behaviour of the person with dementia over time, managing conflicting (medical) advice about these discrepancies and reinterpreting their relationships with hindsight. The sense-making concept offers a more constructive hermeneutic than the ‘family crisis’ narrative as it illuminates the agency of carers’ in understanding changed behaviours, negotiating services and managing personal, social and structural barriers pre-diagnosis. The concept also demonstrates the need for a multimodal approach to promoting timely diagnosis of dementia in ethnic minority communities through dementia awareness and literacy campaigns as well as initiatives that address structural inequities.
Digital technologies in policy assemblages in Ireland and Norway: A visual network analysis
Authors: Lunde Ida M , Ottesen Eli
Published: November 2020

Increasingly, school leaders and teachers are being expected to use digital technologies to collect data to analyze, plan and organize teaching and learning. Such expectations can be traced to a number of policy initiatives over the last decade. This study is concerned with how educational policy puts forward ambitions of digital school leadership and teaching practices by deploying the concept of policy assemblage. We analyzed six policy documents from Ireland and Norway to identify the actors assembled to fulfill governmental ambitions and practices with digital technologies in schools. The unpacking of actors that may partake in such assemblages was visualized and analyzed using visual network analysis. The findings indicate digital school leadership and teaching practices in Ireland and Norway have the potential to be steered by digital actors that facilitate multiple activities at once and shed light on the diverse and multifaceted relationships that make up these governing practices.
Machine learning paradigm for structural health monitoring
Authors: Bao Yuequan , Li Hui
Published: November 2020

Structural health diagnosis and prognosis is the goal of structural health monitoring. Vibration-based structural health monitoring methodology has been extensively investigated. However, the conventional vibration–based methods find it difficult to detect damages of actual structures because of a high incompleteness in the monitoring information (the number of sensors is much fewer with respect to the number of degrees of freedom of a structure), intense uncertainties in the structural conditions and monitoring systems, and coupled effects of damage and environmental actions on modal parameters. It is a truth that the performance and conditions of a structure must be embedded in the monitoring data (vehicles, wind, etc.; acceleration, displacement, cable force, strain, images, videos, etc.). Therefore, there is a need to develop completely novel structural health diagnosis and prognosis methodology based on the various monitoring data. Machine learning provides the advanced mathematical frameworks and algorithms that can help discover and model the performance and conditions of a structure through deep mining of monitoring data. Thus, machine learning takes an opportunity to establish novel machine learning paradigm for structural health diagnosis and prognosis theory termed the machine learning paradigm for structural health monitoring. This article sheds light on principles for machine learning paradigm for structural health monitoring with some examples and reviews the existing challenges and open questions in this field.
Increased alpha and beta cell mass during mouse pregnancy is not dependent on transdifferentiation
Authors: Szlapinski Sandra K , Bennett Jamie , Strutt Brenda J , Hill David J
Published: November 2020

Maternal pancreatic beta-cell mass (BCM) increases during pregnancy to compensate for relative insulin resistance. If BCM expansion is suboptimal, gestational diabetes mellitus can develop. Alpha-cell mass (ACM) also changes during pregnancy, but there is a lack of information about α-cell plasticity in pregnancy and whether α- to β-cell transdifferentiation can occur. To investigate this, we used a mouse model of gestational glucose intolerance induced by feeding low-protein (LP) diet from conception until weaning and compared pregnant female offspring to control diet-fed animals. Control and LP pancreata were collected for immunohistochemical analysis and serum glucagon levels were measured. In order to lineage trace α- to β-cell conversion, we utilized transgenic mice expressing yellow fluorescent protein behind the proglucagon gene promoter (Gcg-Cre/YFP) and collected pancreata for histology at various gestational timepoints. Alpha-cell proliferation increased significantly at gestational day (GD) 9.5 in control pregnancies resulting in an increased ACM at GD18.5, and this was significantly reduced in LP animals. Despite these changes, serum glucagon was higher in LP mice at GD18.5. Pregnant Gcg-Cre/YFP mice showed no increase in the abundance of insulin+YFP+glucagon– cells (phenotypic β-cells). A second population of insulin+YFP+glucagon+ cells was identified which also did not alter during pregnancy. However, there was an altered anatomical distribution within islets with fewer insulin+YFP+glucagon– cells but more insulin+YFP+glucagon+ cells being present in the islet mantle at GD18.5. These findings demonstrate that dynamic changes in ACM occur during normal pregnancy and were altered in glucose-intolerant pregnancies.
Sense of Belonging and Community Building within a STEM Intervention Program: A Focus on Latino Male Undergraduates’ Experiences
Authors: Abrica Elvira J. , Lane Tonisha B. , Zobac Stephanie , Collins Elizabeth
Published: November 2020

Relying on semi-structured, qualitative interviews with 13 Latino male undergraduates in engineering, this study explored students experiences and sense of belonging within a Minority Retention Program at a 4-year public university in California. Findings support extent research on the importance of structural interventions in science, technology, engineering, and mathematics (STEM) while highlighting nuance in experiences of Latino males, including perceptions of stigma associated with participation. Implications for future research and practice are discussed.
Bilateral Vein Compression by Popliteal Artery Aneurisms Mimicking Post-Thrombotic Syndrome
Authors: Gonzalez-Urquijo Mauricio , Cassagne Gabriela , Lozano-Balderas Gerardo , Fabiani Mario Alejandro
Published: November 2020

Purpose:

To report a case of a 79-year-old man who presented a bilateral popliteal artery aneurysm compressing both popliteal veins mimicking signs and symptoms of post-thrombotic syndrome.

Case Report:

A 79-year-old male patient, was seen in the ambulatory clinic with a 2-year history of bilateral leg swelling, calf pain, chronic ulceration, and hyperpigmentation. Upon physical examination, lower extremities were edematous, with a 3 cm suppurative ulcer on each leg. Image studies showed a popliteal right arterial aneurysm of maximum diameter of 41.7 mm, extrinsically compressing the ipsilateral popliteal vein. Likewise, on the left leg, a popliteal arterial aneurysm of maximum diameter of 47.9 mm was encountered triggering the same phenomenon. Bilateral endovascular treatment deploying stent grafts was auspiciously performed. At 36-months follow up, his symptoms are completely resolved, and his ulcers healed. US follow up showed exclusion of the aneurysms with progressive shrinkage of both residual sacs.

Conclusion:

Popliteal artery aneurysm compressing and constraining flow in the popliteal vein must be included as a differential diagnosis among the causes of chronic venous syndromes. Prompt diagnosis with its appropriate treatment is needed for reducing severe complications caused by PAA, such as the venous disorder our patient had.
Utilization Rates of Diagnostic and Therapeutic Vascular Procedures Among Patients Undergoing Lower Extremity Amputations in a Rural Community Hospital: A Clinicopathological Correlation
Authors: Varghese Joji J. , Estes Bailey Ann , Martinsen Brad J. , Igyarto Zsuzsanna , Mustapha Jihad , Saab Fadi , Naidu Srihari S.
Published: November 2020

Background:

Significant geographical variations exist in amputation rates and utilization of diagnostic and therapeutic vascular procedures before lower extremity amputations in the United States. The purpose of this study was to evaluate the rates of diagnostic and therapeutic vascular procedures in the year prior to amputation in a contemporary population and correlate with pathological findings of the amputation specimens.

Methods:

A retrospective analysis was conducted of non-traumatic amputations from 2011 to 2017 at a rural community hospital. We reviewed the proportion of patients undergoing diagnostic (ankle brachial index with duplex ultrasound, computerized tomography angiogram and invasive angiogram) and therapeutic (endovascular and surgical revascularization) vascular procedures in the year prior to amputation. Prevalence of tissue viability and osteomyelitis were evaluated in all amputated specimens and atherosclerotic vascular disease (ASVD) was evaluated in major amputations. We also analyzed primary amputation rates among different subgroups.

Results:

698 patients were included with 248 (36%) major amputations and 450 (64%) minor amputations. Any diagnostic procedure was performed in 59% of the major amputations and 49% of the minor amputations (P = 0.01). Any therapeutic revascularization procedure was performed in 34% of the major amputations and 28% of the minor amputations (P = 0.08). The pathology of major amputation specimens revealed severe ASVD in 57% and mild-moderate ASVD in 27% of specimens. Tissue viability was significantly higher in major amputations (90% vs 30%, P = 0.04) and osteomyelitis was significantly higher in minor amputations (50% vs 14%, P = 0.03). Primary amputations were performed in 66% of major amputations, 72% of minor amputations, 81% with mild to moderate ASVD and 54% with severe ASVD.

Conclusion:

Diagnostic and therapeutic vascular procedures appear under-utilized for patients undergoing lower extremity amputations at a rural community hospital. ASVD rates and tissue viability imply that revascularization could be of significant benefit to avoid major amputation.
The Epidemiology of Cocaine Use Among Hispanic Individuals: Findings From the 2015–2018 National Survey of Drug Use and Health
Authors: Yockey Andrew , Stryker Shanna
Published: November 2020

Cocaine use disproportionately affects several social groups, including ethnic and sexual minorities. The present study sought to identify the epidemiology of cocaine use among a national sample of Hispanic young adults using pooled data from the 2015–2018 National Survey of Drug Use and Health. Weighted analyses were used to identify correlates to past-year cocaine use. Results revealed that 4.11% ( n = 729) of individuals used cocaine in the past year. Individuals who identified as gay/lesbian or bisexual, who drove under the influence of alcohol in the past year, and who reported prior drug use were at risk of cocaine use. Of concern, nearly 10% of gay/lesbian Hispanic individuals report having used cocaine in the past year. Furthermore, cocaine use was associated with other risky behaviors; 41.1% of LSD (Lysergic acid diethylamide) users also reported cocaine use, and 18.2% of cocaine users reported having driven under the influence of alcohol within the past year. Findings from the present study may inform harm reduction efforts and health prevention messages.
Growth in Adult Ego Development and Mentalizing Emotions for an Increasingly Multidimensional God Image
Authors: Kam Christopher
Published: November 2020

Growth in cognitive complexity in the framework of adult ego development has shown to enable sophistication in mentalizing interpersonal emotions. This has implications for cultivating a more multidimensional God Image for spirituality in the Judeo-Christian tradition. The construct of mentalization will be used to understand the integration of these concepts. Empirical findings that support this conceptual integration will be explored. Clinical applications for spiritually integrated psychotherapy will follow.
The COVID-19 Context Calls for a Broader Range of Healthcare Chaplaincy Models: An Exploratory Translational Study Utilizing Evolutionary Psychology and Social Neuroscience Loneliness Research
Authors: Riggs Ann K.
Published: November 2020

Shifts in chaplain requests from patients and families and lack of engagement by staff in now traditional support forms in the COVID-19 context suggest that new insights and resourcing are needed. This exploratory translational study suggests that the evolutionary psychology of R. I. M. Dunbar and the social neuroscience of J. T. Cacioppo, his collaborators, and successors and their concerns for human loneliness have potential for use in development of effective healthcare chaplaincy practice in the COVID-19 context.
The SOCOM Spiritual Fitness Scale: Measuring “Vertical” and “Horizontal” Spirituality in the Human Performance Domain
Authors: Alexander David William , Abulhawa Zainah , Kazman Joshua
Published: November 2020

Few spiritual scales are tailored to the work of human performance, few enfranchise non-theists, and few simultaneously capture both vertical and horizontal aspects of spirituality. To address the gap, the Consortium for Health and Military Performance partnered with the US Special Operations Command to develop the SOCOM Spiritual Fitness Scale. The scale is reliable, valid, psychometrically sound, and capable of generating comprehensive group and individual profiles to aid chaplains in program development/assessment and tailored spiritual coaching.
Needleless electrospun polyacrylonitrile/konjac glucomannan nanofiber mats
Authors: Mamun Al , Trabelsi Marah , Klöcker Michaela , Lukas Storck Jan , Böttjer Robin , Sabantina Lilia
Published: November 2020

In this study we report for the first time about the preparation of polyacrilontrile (PAN)/konjac glucomannan (KGM) nanofiber mats, needleless electrospinning from the low-toxic solvent dimethyl sulfoxide (DMSO) and the formation of carbon nanocomposites. Konjac glucomannan is a biopolymer and renewable, environmentally friendly raw material and a well-known polysaccharide, which is non-toxic and biocompatible material and is extracted from the Amorphophallus konjac plant. The addition of poloxamer in electrospinning PAN/KGM solution resulted in the reduction of membrane areas and decrease of beads in nanofibers. The concentration of 1.5% or 0.5% of konjac glucomannan in PAN/KGM nanofiber mats was not detected to affect the morphology of the nanofiber mats. The PAN/KGM nanofiber mats received oxidative stabilization and subsequent carbonization. It could be observed that after the oxidative stabilization process the average diameter of PAN/KGM nanofibers increased and after carbonization decreased compared to stabilized nanofibers. Alternative renewable raw materials such as KGM electrospun with synthetic polymers offer the possibility to reduce the environmental impact and are the alternative to new technical materials and lowers the cost of carbon materials. The combination of PAN with konjac glucomannan and the properties of both polymers open up a wide range of applications for the PAN/KGM nanofiber mats and carbon nanocomposites produced in this study, for example, for pharmaceutical and biomedical applications, as absorbents for the removal of pollutants in wastewater and as filter media for air purification, as well as for optical and chemical sensors.
Effect of intermingling process parameters on polyester/nylon melange fabric appearance
Authors: Wickramasinghe GLD , Dolawatte Sameera Umesh , Thebuwana Isuru Udayanga , Botheju WWS Sampath
Published: November 2020

The objective of this research work was to investigate the effect of intermingling process parameters on melange fabric appearance. Results show that the polyester overfeed, nylon overfeed, air pressure, and production speed have significant correlation with melange fabric appearance. Polyester yarn tension and nylon yarn tensions do not show significant effect on melange fabric appearance. Melange appearance varies from stripe to uniform distribution when polyester and nylon overfeeds are increased independently as well as collectively. Therefore, it can be concluded that polyester and nylon overfeed can be used to achieve specific melange appearance as per the customer samples. Optimum air pressure and production speed to be determined during sample development stage since those two parameters are directly link to the production cost; and should be maintained as a constant and controlled during production, since any variation of those two parameters will change appearance of the melange fabrics.
Investigation of Non-fully Similar Laws of Damage to an Arch Dam in Shaking Table Model Tests
Authors: Xu Qiang , Chen Jianyun , Liu Bo , Li Jing
Published: November 2020

In order to overcome the defect that the general shaking table test can’t clarify the scale relationship between the prototype structure and the scale model in the damaged area based on the fully similar laws, we derived a method that can analyze the relationship between the prototype structure and the scale model in the damaged area based on non-fully similar lows and verified it. We selected the appropriate material (the emulation concrete material, ECM), which has a good scale relationship with the prototype material in the elastic stage, the crack appearance stage, and crack propagation stage (damage stage). We proposed some similar ratios to reveal the similar relationship between the prototype structure and the scale model in the elastic stage, the crack appearance stage, and the crack propagation stage. Especially, we proposed two similar ratios: cr and hr (deduced by the fracture toughness similarity requirements and the fracture energy similarity requirements, respectively) which can well reflect the similar relationship between the prototype structure and the scale model in the damaged area. In order to verify these ratios, we compared the results of the prototype structure numerical simulation with those of the shaking table test of the scale model. The results show that hr has higher accuracy for predicting the relationship between the prototype structure and the scale model in the damaged area.
Bayesian biomarker-driven outcome-adaptive randomization with an imperfect biomarker assay
Authors: Garcia Barrado Leandro , Burzykowski Tomasz
Published: November 2020

Objective:

We investigate the impact of biomarker assay’s accuracy on the operating characteristics of a Bayesian biomarker-driven outcome-adaptive randomization design.

Methods:

In a simulation study, we assume a trial with two treatments, two biomarker-based strata, and a binary clinical outcome (response). P bt denotes the probability of response for treatment t ( t = 0 or 1) in biomarker stratum ( b = 0 or 1). Four different scenarios in terms of true underlying response probabilities are considered: a null ( P00 = P01 = 0.25, P10 = P11= 0.25) and consistent ( P00 = P10 = 0.25, P01 = 0.5) treatment effect scenario, as well as a quantitative ( P00 = P01 = P10 = 0.25, P11 = 0.5) and a qualitative ( P00 = P11 = 0.5, P01 = P10 = 0.25) stratum-treatment interaction. For each scenario, we compare the case of a perfect with the case of an imperfect biomarker assay with sensitivity and specificity of 0.8 and 0.7, respectively. In addition, biomarker-positive prevalence values P( B = 1) = 0.2 and 0.5 are investigated.

Results:

Results show that the use of an imperfect assay affects the operational characteristics of the Bayesian biomarker-based outcome-adaptive randomization design. In particular, the misclassification causes a substantial reduction in power accompanied by a considerable increase in the type-I error probability. The magnitude of these effects depends on the sensitivity and specificity of the assay, as well as on the distribution of the biomarker in the patient population.

Conclusion:

With an imperfect biomarker assay, the decision to apply a biomarker-based outcome-adaptive randomization design may require careful reflection.
Details of risk–benefit communication in informed consent documents for phase I/II trials
Authors: Kahrass Hannes , Bossert Sabine , Schürmann Christopher , Strech Daniel
Published: November 2020

Background:

Informed consent documents for clinical studies should disclose all reasonably foreseeable risks and benefits. Little guidance exists on how to navigate the complexities of risk–benefit communication, especially in early clinical research. Practice-oriented development of such guidance should be informed by evidence on what and how details of risks and benefits are currently communicated.

Method:

We surveyed the responsible parties of phase I/II trials registered in ClinicalTrials.gov that started 2007 or later and completed between 2012 and 2016 to sample informed consent documents from a broad spectrum of early phase clinical trials. Based on an assessment matrix, we qualitatively and quantitatively assessed the informed consent documents for details of risk–benefit communication.

Results:

The risk–benefit communication in the 172 informed consent documents differed substantially in several regards. The outcome, extent, and likelihood of health risks, for example, were described in 83%, 32%, and 63% of the informed consent documents. Only 45% of informed consent documents specified the outcome of mentioned health benefits, and the extent and likelihood of health benefits were never specified. From those informed consent documents reporting risk likelihoods, only 57% added frequency numbers to words such as “common” or “rare,” and even in these cases, we found strong variations for presented frequency ranges. Substantial heterogeneity also exists for how informed consent documents communicate other risk and benefit types and related safeguards.

Conclusion:

Our study points to several shortcomings and heterogeneities in how informed consent documents communicate risks and benefits to potential research participants. Health risks, for example, should be specified with frequency numbers, and health benefits should be specified at least by mentioning their outcomes. Further demand for research and policy development is needed to harmonize risk–benefit communication and to clarify ways to specify the likelihood of health benefits.
Event-specific win ratios and testing with terminal and non-terminal events
Authors: Yang Song , Troendle James
Published: November 2020

Background/aims

In clinical trials, the primary outcome is often a composite endpoint defined as time to the first occurrence of either death or certain non-fatal events. Thus, a portion of available data would be omitted. In the win ratio approach, priorities are given to the clinically more important events, and more data are used. However, its power may be low if the treatment effect is predominantly on the non-terminal event.

Methods

We propose event-specific win ratios obtained separately on the terminal and non-terminal events. They can then be used to form global tests such as a linear combination test, the maximum test, or a [Formula: see text] test.

Results

In simulations, these tests often improve the power of the original win ratio test. Furthermore, when the terminal and non-terminal events experience differential treatment effects, the new tests are often more powerful than the log-rank test for the composite outcome. Whether the treatment effect is primarily on the terminal events or not, the new tests based on the event-specific win ratios can be useful when different types of events are present. The new tests can reject the null hypothesis of no difference in the event distributions in the two treatment arms with the terminal event showing detrimental effect and the non-terminal event showing beneficial effect. The maximum test and the [Formula: see text] test do not have test-estimation coherency, but the maximum test has the coherency that the global null is rejected if and only if the null for one of the event types is rejected. When applied to data from the trial Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function (TOPCAT), the new tests all reject the null hypothesis of no treatment effect while both the log-rank test used in TOPCAT and the original win ratio approach show non-significant p-values.

Conclusion

Whether the treatment effect is primarily on the terminal events or the non-terminal events, the maximum test based on the event-specific win ratios can be a useful alternative for testing treatment effect in clinical trials with time-to-event outcomes when different types of events are present.
Economic evaluation of extended electrocardiogram monitoring for atrial fibrillation in patients with cryptogenic stroke
Authors: Chew Derek S , Rennert-May Elissa , Quinn F Russell , Buck Brian , Hill Michael D , Spackman Eldon , Manns Braden J , Exner Derek V
Published: November 2020

Background

Timely identification of occult atrial fibrillation following cryptogenic stroke facilitates consideration of oral anticoagulation therapy. Extended electrocardiography monitoring beyond 24 to 48 h Holter monitoring improves atrial fibrillation detection rates, yet uncertainty remains due to upfront costs and the projected long-term benefit. We sought to determine the cost-effectiveness of three electrocardiography monitoring strategies in detecting atrial fibrillation after cryptogenic stroke.

Methods

A decision-analytic Markov model was used to project the costs and outcomes of three different electrocardiography monitoring strategies (i.e. 30-day electrocardiography monitoring, three-year implantable loop recorder monitoring, and conventional Holter monitoring) in acute stroke survivors without previously documented atrial fibrillation.

Results

The lifetime discounted costs and quality-adjusted life years were $206,385 and 7.77 quality-adjusted life years for conventional monitoring, $207,080 and 7.79 quality-adjusted life years for 30-day extended electrocardiography monitoring, and $210,728 and 7.88 quality-adjusted life years for the implantable loop recorder strategy. Additional quality-adjusted life years could be attained at a more favorable incremental cost per quality-adjusted life year with the implantable loop recorder strategy, compared with the 30-day electrocardiography monitoring strategy, thereby eliminating the 30-day strategy by extended dominance. The implantable loop recorder strategy was associated with an incremental cost per quality-adjusted life year gained of $40,796 compared with conventional monitoring. One-way sensitivity analyses indicated that the model was most sensitive to the rate of recurrent ischemic stroke.

Conclusions

An implantable loop recorder strategy for detection of occult atrial fibrillation in patients with cryptogenic stroke is more economically attractive than 30-day electrocardiography monitoring compared to conventional monitoring and is associated with a cost per quality-adjusted life year gained in the range of other publicly funded therapies. The value proposition is improved when considering patients at the highest risk of recurrent ischemic stroke. However, the implantable loop recorder strategy is associated with increased health care costs, and the opportunity cost of wide scale implementation must be considered.
Kinetics of changes in gene and microRNA expression related with muscle inflammation and protein degradation following LPS-challenge in weaned piglets
Authors: Kang Ping , Huang Xingfa , Wan Zhicheng , Liang Tianzeng , Wang Yang , Li Xiangen , Zhang Jing , Zhu Huiling , Liu Yulan
Published: November 2020

To test the dynamic changes of the expression of genes and microRNA in the gastrocnemius muscle after LPS challenge, 36 piglets were assigned to a control group (slaughtered 0 h after saline injection) and LPS groups (slaughtered at 1 h, 2 h, 4 h, 8 h, and 12 h after LPS treatment, respectively). After LPS treatment, the mRNA expression of IL-1β, IL-6, and TNF-α reached maximal levels at 1 h, 2 h, and 1 h, respectively ( P < 0.05), and mRNA expression of TLR4, NODs, muscle-specific ring finger 1, and muscle atrophy F-box peaked at 12 h ( P < 0.05). Moreover, the expression of miR-122, miR-135a, and miR-370 reduced at 1 h, 1 h, and 2 h, respectively ( P < 0.05), and miR-34a, miR-224, miR-132, and miR-145 reached maximum expression levels at 1 h, 1 h, 2 h, and 4 h, respectively ( P < 0.05). These results suggested that mRNA expression of pro-inflammatory cytokines was elevated in the early stage, mRNA expression of genes related to TLR4 and NODs signaling pathways and protein degradation increased in the later phase, and the expression of microRNA related to muscle inflammation and protein degradation changed in the early stage after LPS injection.
A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
Authors: Si Xiaoyan , Wang Jinwan , Cheng Ying , Shi Jianhua , Cui Liying , Zhang Helong , Huang Yunchao , Liu Wei , Chen Lei , Zhu Jiang , Zhang Shucai , Li Wei , Sun Yan , Wang Hanping , Zhang Xiaotong , Wang Mengzhao , Yang Lin , Zhang Li
Published: November 2020

Background:

Carboxyamidotriazole (CAI), a calcium channel blocker, inhibits tumor cell proliferation, metastasis, and angiogenesis. This trial aimed to determine whether CAI combined with conventional chemotherapy could prolong progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients.

Methods:

Patients were assigned into groups (3:1 ratio) to receive either chemotherapy + CAI or chemotherapy alone. Cisplatin (25 mg/m2) was administered by intravenous infusion on days 1, 2, and 3, and vinorelbine (25 mg/m2) on days 1 and 8 of each 3-week cycle for four cycles. CAI was administered at 100 mg daily with concomitant chemotherapy; this treatment was continued after chemotherapy was ceased until serious toxicity or disease progression had occurred. PFS was the primary endpoint, and the secondary endpoints were objective response rate (ORR), disease control rate, overall survival (OS), and quality of life.

Results:

In total, 495 patients were enrolled in the trial: 378 in the chemotherapy + CAI group and 117 in the chemotherapy + placebo group. PFS was significantly greater in the chemotherapy + CAI [median, 134 days; 95% confidence interval (CI) 127–139] than in the chemotherapy + placebo (median, 98 days; 95% CI: 88–125) group, with a hazard ratio of 0.690 (95% CI: 0.539–0.883; p = 0.003). There was no difference in the OS rates of both groups. The ORR was greater in the chemotherapy + CAI group than in the chemotherapy + placebo group (34.6% versus 25.0%, p = 0.042). Adverse events of ⩾grade 3 occurred more frequently in the CAI group [256 (68.1%) versus 64 (55.2%); p = 0.014].

Conclusion:

CAI + platinum-based chemotherapy prolonged PFS and could be a useful therapeutic option to treat NSCLC.

Clinical Trial Registration:

chinadrugtrials.org.cn identifier: CTR20160395
Success of Honors Program in Azerbaijan: Do Honors Students Perform Better Than Nonhonors Students?
Authors: Abizada Azar , Mirzaliyeva Fizza
Published: November 2020

The purpose of launching honors programs in Azerbaijan was not only to introduce advanced academic programs but also to change the culture in the universities: to make students more socially active, to encourage them to participate in international competitions, and continue their education. Keeping these goals in mind, we evaluate honors programs by comparing honors students and nonhonors students in respective universities by (a) academic performance, (b) future academic goals, and (c) participation in extracurricular activities. We showed that when we look at academic performance, future academic goals, and some of the extracurricular activities, honors students clearly outperform nonhonors students.
Hepatoprotective Effect of the Fruits of Polygonum orientale L. Against Carbon Tetrachloride-Induced Liver Fibrosis in Mice
Authors: Chiu Yung-Jia , Wu Kun-Chang , Tsai Jen-Chieh , Kao Chun-Pin , Chao Jung , Peng Wen Huang , Cheng Hao-Yuan
Published: November 2020

The aim of this study was to evaluate the hepatoprotective effects of the fruits of Polygonum orientale L. (POE) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury. Bioactive components of POE were identified using liquid chromatography (LC)-mass spectrometry (MS)/MS by comparison with standards. Treatment with either silymarin (200 mg/kg) or POE (0.5 and 1.0 g/kg) caused significant decreases in the serum levels of enzymes and reduced the extent of liver lesions and fibrosis in histological analysis. POE (0.5 and 1.0 g/kg) decreased the levels of malondialdehyde, nitric oxide, proinflammatory cytokines (ie, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6), an inflammatory cytokine (ie, cyclooxygenase-2), a profibrotic cytokine (ie, transforming growth factor-β), and fibrosis-related proteins (ie, connective tissue growth factor and α-smooth muscle actin) in the liver and enhanced the activities of the antioxidative enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. Quantitative analysis of the active constituents in POE revealed an extract composition of 3.4 mg/g of protocatechuic acid, 20.8 mg/g of taxifolin, and 5.6 mg/g of quercetin. We have demonstrated that the hepatoprotective mechanisms of POE are likely to be associated with the decrease in inflammatory cytokines by increasing the activities of antioxidant enzymes. Our findings provide evidence that POE possesses a hepatoprotective activity to ameliorate chronic liver injury.
Diagnostic Yield of Neck CT Angiography in Young Adults With Anterior Circulation Ischemic Stroke: A Community Based Study
Authors: Schenk William B. , Brinjikji Waleed , Larson Anthony S. , Nasr Deena M.
Published: November 2020

Background and Purpose:

Few community-based studies investigating young adult strokes exist. The aim of this study was to determine the diagnostic yield of head and neck CTA in evaluation of anterior circulation ischemic stroke in young adults.

Materials and Methods:

This retrospective review is limited to patients between the ages of 18-50 presenting to the Mayo Clinic Rochester emergency department or referred from smaller institutions in adjacent counties. Patients with posterior circulation infarcts, amaurosis fugax, central retinal artery occlusion or transient ischemic attacks were excluded. The presence of carotid dissection, webs, plaque, or other high-risk lesions were recorded.

Results:

A total of 136 patients met inclusion criteria. Mean degree of carotid stenosis ipsilateral to infarct was 14.1%, compared to 6.5% on the contralateral side (p = .006). Ipsilateral mean carotid wall thickness measured .79 mm, compared to contralateral thickness of .80 mm (p = .51). Ipsilateral low-density plaque was observed in 22 patients (16.2%), and 21 patients (15.4%) on the contralateral side (p = .87). Ipsilateral calcified plaque was observed in 37 patients (27.2%), and 29 patients (21.3%) on the contralateral side (p = .31). 20 (14.7%) ipsilateral dissections were noted, compared to 4 (2.9%) contralateral dissections (p = .001). 3 (2.2%) ipsilateral carotid webs were identified, compared to 0 contralateral webs (p = .25).

Conclusion:

Carotid dissection was the most common cause of anterior circulation infarct identified on cervical CTA in this population. Carotid webs and atherosclerosis were not common findings.
Primary squamous cell carcinoma of major salivary gland: “Sapienza Head and Neck Unit” clinical recommendations
Authors: Mezi Silvia , Pomati Giulia , Botticelli Andrea , De Felice Francesca , Musio Daniela , della Monaca Marco , Amirhassankhani Sasan , Vullo Francesco , Cerbelli Bruna , Carletti Raffaella , Di Gioia Cira , Catalano Carlo , Valentini Valentino , Tombolini Vincenzo , Della Rocca Carlo , Marchetti Paolo
Published: November 2020

Primary squamous cell carcinoma of salivary gland (SCG) is an extremely rare type of malignant salivary gland tumor, which in turn results in scarcity of data available regarding both its treatment and associated genetic alterations. A retrospective analysis of 12 patients with primary SCG was conducted, along with analysis of the association between treatment, clinical/pathological characteristics, and outcomes. Most patients (8) were staged IVa, with the majority of them (10) having G3 fast growing cancer. Local and systemic recurrence were reported in only three out of nine parotid cases (0 out of 2 submandibular SCGs). In two out of eight patients local relapse occurred after integrated treatment, while recurrence occurred in two out of three patients undergoing exclusive surgery. Five patients eventually died. Treatment of resectable disease must be aggressive and multimodal, with achievement of loco-regional control in order to reduce rate of recurrence and improve outcomes. Metastatic disease would require a therapeutic strategy tailored to the molecular profile in order to improve the currently disappointing results.
Going Out and About: Activating children as citizens of the now
Authors: Iorio Jeanne Marie , Hamm Catherine , Krechevsky Mara
Published: November 2020

This article shares two research projects in the United States and Australia where children and teachers lead their local communities towards living well in precarious times. Rooted in the image of ‘children as citizens of the now’, the research projects offer innovative pedagogies as a way for children to generate meaningful relationships with community and local places. Specifically, children, families, teachers and researchers bring questions and curiosities from their everyday lives that activate teaching and learning with and from the world through the concepts of slowing down, noticing and engaging with multiple perspectives.