bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Simulation-Optimization Framework for Assessing the Impact of I-66 Dynamic Toll Pricing on Pavement Deterioration and Maintenance Decisions
Authors: Abi Aad Mirla , Abbas Montasir
Published: July 2022

Tolled facilities are undoubtedly expected to alter the distribution of traffic across the transportation network. On the other hand, traffic volumes and loading have an impact on deteriorating pavement conditions. These traffic volumes are considered by Departments of Transportation (DOTs) while allocating annual budgets to maintain and rehabilitate roadway segments to sustain pavement performance targets. This research studies the specific site around I-66 inside the Beltway, which newly applied dynamic tolls during a.m. and p.m. peak hours. An integrated traffic-management/pavement-treatment framework was applied to address both the operational and the pavement performance of the network. Aimsun hybrid macro/meso dynamic user equilibrium experiments were used to simulate the network with the modified cost function taking care of the dynamic pricing along the I-66 tolled facility. An optimization was Python-coded into a Pyomo framework to specify the optimal maintenance and rehabilitation treatment plan, taking into account critical condition index (CCI) deterioration based on the traffic load distribution on the network. Finally, the results of the simulation showed the importance of having an optimized treatment schedule to achieve optimal pavement performance outcomes, with a difference in CCI index that could range all the way from 68 to 95.
Agent-Based Model of Electric Vehicle Charging Demand for Long-Distance Driving in the State of Indiana
Authors: Chen Donghui , Kang Kyubyung , Koo Dan Daehyun , Peng Cheng , Gkritza Konstantina , Labi Samuel
Published: July 2022

Historically the U.S. transportation system has been continuously improved to adopt new policies and technologies. The transportation vehicle energy transition from fossil fuels to electricity is promoted by policymakers and major automakers with an expectation of enhancing sustainability aspects such as fossil fuel consumption reduction, carbon emissions reduction, and lower operations and maintenance costs. However, the electrification of the existing transportation infrastructure system requires substantial upgrades to overcome two major concerns from ordinary drivers and the public. One is the driver’s range anxiety based on the current capability of the electric vehicle (EV) technologies. The other is the availability of EV charging stations near the planned route. To address these two issues, we introduce an agent-based simulation model to project the consequences of electrification in the Indiana state highway system. Specifically, the model is developed to monitor the status of long-distance EV trips between different regions. The multi-agent engine method guarantees the model can adapt to diverse scenarios and complex environments. The simulation experiment verifies that the proposed model can provide the expected outcomes, including the numerical data of electric energy demand and the geospatial information (as location coordinates) of failed trips. By performing a GIS-based analysis of the results, the derived geospatial data can help state transportation agencies determine where to deploy the charging facilities to satisfy the overall charging demand. The proposed simulation framework offers a novel and strategic way to resolve the challenges for EV charging-related research and projects.
Planning for Speed in the Public Space: The Case of Speed E-bikes in France, Belgium, and Switzerland
Authors: Bajolle Hadrien , Chrétien Julie , Lagadic Marion , Louvet Nicolas
Published: July 2022

Speed e-bikes are electrically assisted pedal cycles with a speed of up to 45 km/h. Because of their high speed, these vehicles are not classified as bicycles in the European Union. However, their external aspect and their mode of propulsion—the user needs to pedal for the electric assistance to work—make them part of the symbolic universe of bicycles. This raises the following question: should these vehicles ride on cycle lanes, or on the road? The authors argue that answering this question implies understanding both how these vehicles are used, and how speed e-bike users perceive themselves. How do users experience their high-velocity bikes? Using qualitative interviews with speed e-bike users in France, Belgium, and Switzerland, this research offers novel data on the actual usage of this emerging mode of transport and what it represents symbolically to users. Results show that speed e-bike users consider themselves as cyclists and value the opportunity to ride on cycle lanes, whether this is allowed or not. However, they self-regulate their positioning on the road depending on their actual speed. When they want to accelerate, speed e-bike users tend to leave bike lanes to ensure their own safety as well as that of other cyclists. These results allow a case to be made for a speed-based regulation according to which riders could use different segments of the public space alternatively depending on their actual speed at a given moment.
Analysis of Washington State Department of Transportation Risks
Authors: Dicks Evan P. , Molenaar Keith R.
Published: July 2022

Risk management is an important part of ensuring the successful delivery of major transportation projects. The first step in the risk management process is to identify the risks facing the project team so they can proactively complete the remaining steps: analyzing the severity; choosing how to respond; and controlling the level of risk throughout the lifecycle of the project. Although some state agencies have been practicing risk management for nearly two decades, little analysis of the risks identified during project development has been done. This study analyzes the risk registers pertaining to 51 major transportation projects undertaken by the Washington State Department of Transportation valued at approximately $7.7 billion to determine the distribution of risks among categories in the risk breakdown structure and find the most common risks in each category. The findings were then explored through interviews with industry professionals to gain insight into the results, add context, and illustrate the importance of identified risks. The results contribute to a better understanding of the risks facing transportation departments and lay the foundation for a more comprehensive risk identification step at the project level.
Hip Arthroscopy for the Treatment of Femoroacetabular Impingement Syndrome in Hips With Mild Osteoarthritis (Tönnis Grade 1): A Matched Comparative Cohort Analysis at Minimum 5-Year Follow-up
Authors: Sivasundaram Lakshmanan , Rice Morgan W. , Horner Nolan S. , Alter Thomas D. , Ephron Christopher G. , Nho Shane J.
Published: July 2022

Background:

There is a paucity of information in the literature on midterm outcomes from the arthroscopic treatment of femoroacetabular impingement syndrome (FAIS) with concomitant labral treatment in patients with mild osteoarthritis (OA) using modern surgical techniques.

Purpose:

To compare outcomes of hip arthroscopy for the treatment of FAIS between patients with mild OA (Tönnis grade 1) and patients without OA (Tönnis grade 0) at minimum 5-year follow-up.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Patients were identified who underwent primary hip arthroscopy for FAIS with routine capsular closure between January 2012 and December 2015. Patients with Tönnis grade 1 were matched 1:3 by age, sex, and body mass index to patients without OA. The Hip Outcome Score–Activities of Daily Living (HOS-ADL), HOS–Sports Subscale (HOS-SS), modified Harris Hip Score, and 12-item International Hip Outcome Tool were collected preoperatively and at 5 years postoperatively and compared between groups using an independent t test. Survivorship rate and percentage achievement of a Patient Acceptable Symptom State (PASS) or minimal clinically important difference (MCID) were compared using a Fisher exact test.

Results:

A total of 50 patients (54 hips) with Tönnis grade 1 were matched to 162 patients (162 hips) with Tönnis grade 0. The mean ± SD age and body mass index of the Tönnis grade 1 group were 44.5 ± 9.6 years and 28.5 ± 5.5, respectively. Patient-reported outcome (PRO) scores improved significantly for both groups from presurgery to 5 years postoperatively for all PROs ( P≤ .03). There were no significant differences in preoperative PROs between the groups. Patients with Tönnis grade 1 had significantly lower postoperative scores on the HOS-ADL (74.7 ± 22.6 vs 83.0 ± 20.1; P = .04) and HOS-SS (58.8 ± 33.7 vs 71.8 ± 29.3; P = .03) than patients with grade 0. Patients with Tönnis grade 1 also had significantly lower rates of achievement of the MCID (57.1% vs 80.2%; P < .01) and PASS (34.1% vs 53.4%; P = .03) for any PRO when compared with patients with Tönnis grade 0. Gross survivorship was significantly lower for Tönnis grade 1 versus grade 0 (77.8% vs 96.9%; P < .001).

Conclusion:

Patients with Tönnis grade 1 arthritis experienced significant improvement in PROs after hip arthroscopy for the treatment of FAIS. However, they had significantly lower postoperative HOS-ADL and HOS-SS scores with significantly lower rates of achievement on the MCID and PASS, with a significantly lower gross survivorship rate at a minimum 5 years postoperatively in comparison with those with Tönnis grade 0 changes.
Comparative Effects of Exosomes and Ectosomes Isolated From Adipose-Derived Mesenchymal Stem Cells on Achilles Tendinopathy in a Rat Model
Authors: Xu Tengjing , Lin Yunting , Yu Xinning , Jiang Guangyao , Wang Jiajie , Xu Kaiwang , Fang Jinghua , Wang Siheng , Dai Xuesong
Published: July 2022

Background:

Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have gained momentum as a treatment for tendinopathy. Multiple studies have demonstrated significant differences in cargo composition between the 2 subtypes of MSC-EVs (ie, exosomes and ectosomes), which may result in different therapeutic effects. However, the effects of the 2 EV subtypes on tendinopathy have not yet been compared.

Purpose:

To compare the effects of adipose stem cell–derived exosomes (ASC-Exos) and ectosomes (ASC-Ectos) on Achilles tendinopathy.

Study Design:

Controlled laboratory study.

Methods:

Rats were administered collagenase injections to generate a model of Achilles tendinopathy. A week later, 36 rats were randomly assigned to 3 groups. In each group, Achilles tendons were injected with equal volumes of ASC-Exos, ASC-Ectos, or saline (12 legs/group). The healing outcomes were evaluated by magnetic resonance imaging, histology, immunohistochemistry, transmission electron microscopy, and biomechanical testing at 3 and 5 weeks after collagenase injection.

Results:

At 3 and 5 weeks, the ASC-Exo group had better histological scores ( P = .0036 and P = .0276, respectively), a lower fibril density ( P < .0001 and P = .0310, respectively), and a larger collagen diameter ( P = .0052 and P < .0001, respectively) than the ASC-Ecto group. At 5 weeks, the expression of collagen type 1 and CD206 in the ASC-Exo group was significantly higher than that in the ASC-Ecto group ( P = .0025 and P = .0010, respectively). Regarding biomechanical testing, the ASC-Exo group showed higher failure load ( P = .0005), tensile stress ( P < .0001), and elastic modulus ( P < .0001) than the ASC-Ecto group.

Conclusion:

ASC-Exos had more beneficial effects on tendon repair than ASC-Ectos in a rat model of Achilles tendinopathy.

Clinical Relevance:

Administration of ASC-EVs may have the potential to treat Achilles tendinopathy, and delivery of ASC-Exos could provide additional benefits. It is necessary to compare the healing responses caused by different EV subtypes to further understand their effects on tendinopathy and to aid clinical decision making.
Comparison of Acetabular Measurements Between 2 Validated Software Programs Used in Hip Preservation Surgery
Authors: Laboudie Pierre , Fischman Daniel , Speirs Andrew D. , Salih Saif , Holc Fernando , Beaule Paul E. , Witt Johan D. , Grammatopoulos George
Published: July 2022

Background:

Validated software tools (Clinical Graphics [CG] and Hip2Norm) permit measurement of the percentage of femoral head coverage (%FHC), which aids in morphological classification and prediction of outcome after hip preservation surgery.

Purpose:

(1) To assess whether acetabular parameter measurements determined from 2 commonly used software systems are comparable. (2) To determine which parameters influence the correlation or differences between software outputs and measurements.

Study Design:

Cohort study (diagnosis); Level of evidence, 2.

Methods:

The study included 69 patients (90 hips) who underwent periacetabular osteotomy and had comprehensive preoperative imaging available. Lateral center-edge angle (LCEA), acetabular index (AI), and %FHC were determined using 3-dimensional computed tomography (CT) measurements by CG and Hip2Norm software. Images of 18 pelvises were segmented to determine spinopelvic parameters and subtended acetabular angles. Between-group measurements were compared using correlation coefficients and Bland-Altman analyses. The difference in the outputs of the 2 programs was defined as delta (Δ). Radiographic parameters were tested to assess whether they were responsible for differences in %FHC between software programs.

Results:

Strong correlations between LCEA (ρ = 0.862) and AI (ρ = 0.825) measurements were seen between the Hip2Norm and CG programs. However, weak correlation was seen in the estimate of %FHC (ρ = 0.358), with the presence of a systematic error. Hip2Norm consistently produced lower anterior, posterior, and total %FHC values than CG. The %FHC determined by CG, but not Hip2Norm, correlated with acetabular subtended angles ( P < .05). Pelvic tilt measured on CT did not correlate with pelvic tilt estimated by Hip2Norm ( P = .56), and ΔPelvicTilt strongly correlated with the difference in %FHC by the 2 software programs (ρ = 0.63; P = .005), pelvic incidence (ρ = 0.73; P < .001), and pelvic tilt (ρ = −0.91; P < .001) as per CT.

Conclusion:

The correlation of %FHC between Hip2Norm and CG was weak (ρ = 0.358). The difference in measurements of %FHC correlated with ΔPelvicTilt. The %FHC determined by CG strongly correlated with the segmented acetabular subtended angles and thus more likely reflected true values. Hip preservation surgeons should be aware of these measurement differences because %FHC is important in the diagnosis and prognosis of acetabular dysplasia.
Biomechanical performance of the cemented acetabular cup with combined effects of bone quality, implant material combinations and bodyweight
Authors: Kumar Ajay , Mondal Subrata , Ghosh Rajesh
Published: July 2022

The objective of this study is to understand the combined effects of bone quality, implant materials and bodyweight on the biomechanical performance of cemented acetabular cup. Additionally, the performance of the cemented acetabular cup was evaluated for obesity cases or obese people. A total of 84 FE models (based on CT data) were developed based on combinations of three different cancellous bone material distributions to represent bone quality, four different implant material combinations and seven different bodyweights. The biomechanical performance of the acetabular cup was evaluated based on bone stress (both cortical and cancellous bone), cement mantle stress, micromotion and contact pressure between the acetabular cup and femoral head. Cortical bone stress, cancellous bone stress, cement stress, the contact pressure between implants and micromotion between implants are affected by different bone quality, implant material combinations and bodyweights. An increase in bodyweight would increase the cortical bone stress, cancellous bone stress, cement stress, contact pressure between implants and micromotion between implants. However, bodyweight affects the cortical and cancellous bone stress more (stiff rise of the bone stresses; nonlinear relation) as compared to other output parameters (mostly linear relation). Comparing cortical and cancellous bone stress, the stress versus bodyweight curve is much stiffer (stiff rise in the curve) for cortical bone than cancellous bone and that even further increases as bone quality decreases. Especially considering obesity cases or obese people (very high bodyweight), the performance of the cemented acetabular component is poor.

Graphical abstract

[Formula: see text]
Women in Cantonments: Evolution of Regulated Military Prostitution in Colonial India
Authors: Mondal Sonia
Published: July 2022

From the mid-19th century the existence of a large number of native prostitutes in the British military cantonments confirmed the widespread prevalence of state-authorised prostitution in colonial India. The colonial administration induced new laws that tried to restrict prostitution as a practice exclusively for the service of the British military men and also made it a sanctioned part of the military establishment. Consequently, a new form of regulated military prostitution evolved that radically changed the nature of prostitution as it used to be in the pre-colonial period.

In this article, I have tried to explore the causes behind the emergence of regulated military prostitution and how it was implemented and systematised in British India. It would also focus on a new pattern of brothel life which emerged throughout military cantonments and finally the women’s life in cantonments that would provide a glimpse of their daily chores and challenges.
Presence Without Empowerment?: Women in Rural Local Government in Bangladesh
Authors: Ahmed Nishat Afroze , Md. Mohiuddin
Published: July 2022

This article explores the role of reserved-seat women members of the Union Parishad, the lowest unit of local government in Bangladesh. The number of women representatives has increased manifold over the years, most of whom are elected from reserved seats. Formally, a reserved-seat member has a larger constituency than a general seat member; and enjoys almost similar powers and responsibilities. In practice, there remains a major gap between what the rules say and what transpires on the ground. Notwithstanding their increased presence, women elected from reserved seats to the Union Parishad, often find it difficult to make their presence felt and are ignored, especially by their male colleagues, for several reasons. This article identifies those reasons and argues that women’s increased presence is a necessary but not a sufficient condition of empowerment. Legitimacy gained through winning elections in a competitive process and the willingness of the elected women to get things done in an adversarial situation can be considered important steps towards empowerment. Nonetheless, more is needed, especially organised support from outside, to enhance empowerment and make it sustainable.
A thermodynamical model for paleomagnetism in Earth’s crust
Authors: Roubíček Tomáš
Published: July 2022

A thermodynamically consistent model for soft deformable viscoelastic magnets is formulated in actual space (Eulerian) coordinates. The possibility of a ferro-paramagnetic-type (or ferri-antiferromagnetic) transition exploiting the Landau phase-transition theory as well as mechanical melting or solidification is considered, being motivated and applicable to paleomagnetism (involving both thermo- and isothermal and viscous remanent magnetization) in rocks in Earth’s crust and to rock-magma transition. The temperature-dependent Jeffreys rheology in the deviatoric part combined with the Kelvin-Voigt rheology in the spherical (volumetric) part is used. The energy balance and the entropy imbalance behind the model are demonstrated, and its analysis is performed by time discretization, proving existence of weak solutions.
Comparison of Lapse Rate in Drug Dependent Patients in 2 Methods of Methadone Maintenance Treatment and Buprenorphine Maintenance Treatment
Authors: Vafaeinasab Mohammadreza , Zare Hamidreza , Dehghani Ali , Malek Seyedehzahra , Dehghani-Tafti Maryam , Sarebanhassanabadi Mohammadtaghi
Published: July 2022

Background:

Lapse has been one of the major challenges in the treatment of drug dependence sometimes leading to its relapse.

Objectives:

The aim of this study was to determine the lapse rate in drug dependent patients as for the 2 methods of methadone maintenance treatment (MMT) and buprenorphine maintenance treatment (BMT) in Yazd city.

Methods:

In this cross-sectional study, 626 female and male patients who had referred to 5 SUD treatment centers in Yazd and had been treated with methadone and buprenorphine maintenance were studied. Participants were divided into 2 groups of MMT and BMT and were evaluated based on lapse within 6 months.

Results:

In this study, 60.9% of patients were treated with methadone but the rest were treated with buprenorphine. Overall, 33.1% of patients lapsed (35.2% for methadone and 29.8%for buprenorphine). Lapse in methadone treatment was correlated with age, occupational status, and duration of treatment ( P < .05); it failed to correlated with any other demographic and clinical characteristics ( P > .05). Lapse rate in buprenorphine treatment was also related to marital status and the drug used ( P < .05). The mean dose of buprenorphine consumed showed no significant relationship with lapse ( P > .05). The results demonstrated that given the low dose, lapse stood higher in the buprenorphine group than the methadone group; however, as to high dose, the buprenorphine group showed lower lapse than the other group.

Conclusions:

In regard with the high rate of lapse, it is recommended to consider the factors related to the 2 methods of treatments, and provide counseling and training programs to lower lapse in the patients. Ethics Committee (REC) approval code: IR.SSU.REC.1394.158.
Racial and Gender Diversity Among Students and Faculty in EHAC-Accredited Environmental Health Sciences Programs: Trend Analysis from 2009 to 2021
Authors: Balanay Jo Anne G , Mitchell Leslie D , Richards Stephanie L
Published: July 2022

Diversity in the environmental health sciences (EHS) workforce is crucial in providing culturally sensitive services to diverse communities. This may be influenced by academic faculty training a diverse student body in the field of environmental health. This study aimed to characterize the diversity of students and faculty in EHS programs accredited by the National Environmental Health Science and Protection Accreditation Council (EHAC). A retrospective analysis was conducted on secondary data obtained from annual surveys administered to program directors in EHAC-accredited academic programs that included both undergraduate and graduate EHS degrees. The database covered surveys on gender and race that were conducted by EHAC for 12 academic years spanning 2009-2010 to 2020-2021. Results show most students (undergraduate and graduate) were female (54.4% and 52.1%, respectively) and white (61.0% and 50.7%, respectively). Increasing trends were observed over the last 12 years (2009-2021) in female undergraduate (from 53.7% to 59.8%) and graduate (from 47.1% to 60.3%) students and in non-white undergraduate students (from 40.0% to 48.2%). Most faculty (teaching in undergraduate and graduate programs) were male (64.4% and 64.3%, respectively) and white (77.9% and 92.1%, respectively). Increasing trends were observed from 2009 to 2021 in female faculty teaching undergraduate (from 27.7% to 42.2%) and graduate (from 31.3% to 42.1%) students. Native American, Alaska Native, Native Hawaiian, and Pacific Islander are consistently the most underrepresented racial groups in both undergraduate and graduate students and faculty. This study provides baseline data on the diversity of students and faculty in EHAC-accredited programs, which is important in informing future research and efforts to increase such diversity. Gender and racial disparity in EHS students and faculty needs to be addressed to provide necessary support to women and non-White constituents by institutional change in culture through active recruitment and by stronger collaboration between professional organizations and minority groups.
Innocence as burden and resource: Adaptation and resistance during wrongful imprisonment
Authors: Umamaheswar Janani
Published: July 2022

Drawing on theoretical scholarship on adaptation and resistance in prisons, I explore the significance and function of innocence—and the acute sense of non-belonging it triggers in the prison setting—in wrongfully-convicted men's responses to imprisonment. Using in-depth interviews with 15 exonerated men in the United States, I argue that innocence functioned as a double-edged sword for the men as they adapted to their wrongful imprisonment: Innocence represented a social and psychological burden as men adjusted to prison life, but it simultaneously facilitated their resistance to formal and informal penal control. Through a discussion of how the men leveraged their innocence to distance themselves psychologically, socially, and symbolically from the prison world, I highlight how, despite being victims of egregious injustice, wrongfully-convicted men are also agentic resistors of the penal system.
Examining Skills and Abilities During the Pandemic – Psychology Students’ and Examiners’ Perceptions of a Digital OSCE
Authors: Hakelind Camilla , Sundström Anna E.
Published: July 2022

Finding valid and reliable ways to assess complex clinical skills within psychology is a challenge. Recently, there have been some examples of applying Objective Structured Clinical Examinations (OSCEs) in psychology for making such assessments. The aim of this study was to examine students’ and examiners’ perceptions of a digital OSCE in psychology regarding quality and students’ feelings about the OSCE. Participants were 51 students enrolled in the Programme for Master of Science in Clinical Psychology during two semesters and nine examiners assessing each OSCE occasion, at Umeå University, Sweden. Web-based questionnaires were used for data collection. Psychometric analyses indicated that the subscales in the student questionnaire had adequate or close to adequate levels of item and scale reliability. Both students and examiners felt that the digital OSCE was realistic, valid and well-aligned with professional practice. Although students perceived the digital OSCE as stressful, the results showed that they were focused and concentrated and found the OSCE to be a positive learning experience, implying that the stress did not affect performance to any significant extent. Based on the examiners’ experiences, it can be concluded that there are both advantages and disadvantages which need to be considered when planning future digital OSCEs.
Unsteady test technique of jet control with multi-parameter coupling
Authors: Xue Fei , Cao Ning , Li Liugang , Zong Xin , Zhao Ling
Published: July 2022

In this paper, the jet control effect of air vehicle is studied, and a new multi parameter coupling unsteady test technique is established, which can ensure that the test model is consistent with the real air vehicle, and the jet is carried out under the condition of complete freedom and no support constraints, so that the wind tunnel test can better simulate the jet control effect of real air vehicle. The new technique overcomes the shortcoming that the previous jet test can only carry out unsteady flow field or unsteady aerodynamic force research, and can ensure that in the whole process of jet flow, the interference flow field at the nozzle, the aerodynamic force of the air vehicle, especially the movement of the air vehicle, are coupled with each other all the time, so as to achieve the same effect as the real air vehicle. The establishment of the new technique overcomes many problems, including the total length of the model is 167 mm, no support for the model, storage of small volume/high-pressure gas in free state, on-time unlocking of sealed gas source in free state of the model, and connection of gas source and nozzle in the model. The test results show that when no jet, the revolution body is head up, which affected by the cavity shock wave. When jet on, the jet force continues to act on the revolution body, resulting in the revolution body lowering its head until it diverges. The new technique can achieve more advanced technical indicators, including: ensuring jet Mach number >1; Ensure that the static pressure ratio of the jet is more than 10 (the static pressure ratio can be greater at hypersonic speed). After the establishment of the new technique, the supersonic wind tunnel test is carried out, and the ideal test results are obtained, which shows that the new technique is reliable.
A platform trial design for preventive vaccines against Marburg virus and other emerging infectious disease threats
Authors: Longini Ira M , Yang Yang , Fleming Thomas R , Muñoz-Fontela César , Wang Rui , Ellenberg Susan S , Qian George , Halloran M Elizabeth , Nason Martha , Gruttola Victor De , Mulangu Sabue , Huang Yunda , Donnelly Christl A , Henao Restrepo Ana-Maria
Published: July 2022

Background:

The threat of a possible Marburg virus disease outbreak in Central and Western Africa is growing. While no Marburg virus vaccines are currently available for use, several candidates are in the pipeline. Building on knowledge and experiences in the designs of vaccine efficacy trials against other pathogens, including SARS-CoV-2, we develop designs of randomized Phase 3 vaccine efficacy trials for Marburg virus vaccines.

Methods:

A core protocol approach will be used, allowing multiple vaccine candidates to be tested against controls. The primary objective of the trial will be to evaluate the effect of each vaccine on the rate of virologically confirmed Marburg virus disease, although Marburg infection assessed via seroconversion could be the primary objective in some cases. The overall trial design will be a mixture of individually and cluster-randomized designs, with individual randomization done whenever possible. Clusters will consist of either contacts and contacts of contacts of index cases, that is, ring vaccination, or other transmission units.

Results:

The primary efficacy endpoint will be analysed as a time-to-event outcome. A vaccine will be considered successful if its estimated efficacy is greater than 50% and has sufficient precision to rule out that true efficacy is less than 30%. This will require approximately 150 total endpoints, that is, cases of confirmed Marburg virus disease, per vaccine/comparator combination. Interim analyses will be conducted after 50 and after 100 events. Statistical analysis of the trial will be blended across the different types of designs. Under the assumption of a 6-month attack rate of 1% of the participants in the placebo arm for both the individually and cluster-randomized populations, the most likely sample size is about 20,000 participants per arm.

Conclusion:

This event-driven design takes into the account the potentially sporadic spread of Marburg virus. The proposed trial design may be applicable for other pathogens against which effective vaccines are not yet available.
The Idiosyncrasy Principle: A New Look at Qualia
Authors: Salti M. , Bergerbest D.
Published: July 2022

In the study of consciousness, qualia, the individual subjective experience, is neglected. It remains impenetrable because the objective perspective used for scientific investigations misses its subjective nature. In 1974, Thomas Nagel suggested that studying qualia requires an “objective phenomenology method” whose goal would be to describe the subjective character of experiences in an independent manner. We introduce a corresponding theoretical and experimental framework based on the “idiosyncrasy principle.” Accordingly, subjectivity depends on the idiosyncratic composition of physical properties to qualia. This allows conceptualizing an idiosyncratic transfer function between the world and its representation. The main challenge in delineating such a transfer function is to come up with an objective measure for another person’s perspective. Numerosity, as opposed to other perceived contents of the physical world, allows reporting subjective experience in an objective manner. On the basis of this unique attribute of numerosity, we suggest a tentative neurocognitive research plan aimed at delineating such idiosyncratic transfer functions, permitting one person to adopt the perspective of another and linking qualia to its mechanism.
Exploring the concept of deep remission in Crohn’s disease: correlation between transmural healing and biomarkers
Authors: Castiglione Fabiana , Imperatore Nicola , Testa Anna , de Sire Roberto , Nardone Olga Maria , Ricciolino Simona , Di Luna Imma , Patturelli Marta , Villani Guido Daniele , Olmo Oriana , Rispo Antonio
Published: July 2022

Background:

While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn’s disease (CD), little is known about the real significance and clinical impact of deep remission (DR).

Objectives:

To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers.

Design:

Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics.

Methods:

A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR.

Results:

Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 μg/g to 260 ± 354.9 μg/g ( p < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 μg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 μg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%).

Conclusion:

An FC < 94 μg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics.
Tocilizumab in visual involvement of giant cell arteritis: a multicenter study of 471 patients
Authors: Loricera Javier , Castañeda Santos , Moriano Clara , Narváez Javier , Aldasoro Vicente , Maiz Olga , Melero Rafael , Villa Ignacio , Vela Paloma , Romero-Yuste Susana , Callejas José L. , de Miguel Eugenio , Galíndez-Agirregoikoa Eva , Sivera Francisca , Fernández-López Jesús C. , Galisteo Carles , Ferraz-Amaro Iván , Sánchez-Martín Julio , Sánchez-Bilbao Lara , Calderón-Goercke Mónica , Casado Alfonso , Hernández José L. , González-Gay Miguel A. , Blanco Ricardo
Published: July 2022

Background:

Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial.

Objective:

We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ.

Design:

This is an observational multicenter study of patients with GCA treated with TCZ.

Methods:

Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision.

Results:

Four hundred seventy-one GCA patients (mean age, 74 ± 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL ( n = 60; unilateral/bilateral: 48/12), TVL ( n = 17; unilateral/bilateral: 11/6), diplopia ( n = 2), and blurred vision ( n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved.

Conclusion:

TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved.
Intensive Olfactory Training in Post-COVID-19 Patients: A Multicenter Randomized Clinical Trial
Authors: Pires Ícaro de A. T. , Steffens Sara T. , Mocelin Aurenzo G. , Shibukawa Debora E. , Leahy Letícia , Saito Fernanda L. , Amadeu Nicole T. , Lopes Natália M. D. , Garcia Ellen C. D. , Albanese Maria L. , De Mari Laura F. , Ferreira Isabel M. , Veiga César A. , Jebahi Yasser , Coifman Herton , Fornazieri Marco A. , Hamerschmidt Rogério
Published: July 2022

Background

Olfactory dysfunction (OD)—including anosmia and hyposmia—is a common symptom of COVID-19. Previous studies have identified olfactory training (OT) as an important treatment for postinfectious OD; however, little is known about its benefits and optimizations after SARS-CoV-2 infection.

Objective

This study aimed to assess whether olfactory training performance can be optimized using more fragrances over a shorter period of time in patients with persistent OD after COVID-19. In addition, we determined the presence of other variables related to OD and treatment response in this population.

Methods

This multicenter randomized clinical trial recruited 80 patients with persistent OD and prior COVID-19 infection for less than 3 months. The patients were divided into 2 groups receiving either 4 or 8 essences over 4 weeks. Subjective assessments and the University of Pennsylvania Smell Identification Test (UPSIT) were performed before and after the treatment.

Results

Significant olfactory improvement was measured subjectively and using the UPSIT in both groups; however, no significant differences between the groups were observed. Additionally, the presence of olfactory fluctuations was associated with higher UPSIT scores.

Conclusion

These data suggest that training intensification by increasing the number of essences for 4 weeks does not show superiority over the classical method. Moreover, fluctuant olfaction seems to be related to a higher score on the UPSIT.
Decrease in Glycosaminoglycan with Aging in Normal Rat Articular Cartilage Is Greater in Females than in Males
Authors: Kobayashi-Miura Mikiko , Osago Harumi , Hamasaki Yoshifumi , Takano Ikuko , Akiho Mitsuki , Hiyoshi Mineyoshi , Hara Nobumasa
Published: July 2022

Objective

Osteoarthritis (OA) is more prevalent in females. We hypothesized that changes in articular cartilage (AC) constituents with aging may cause differences. Herein, we aimed to compare the changes in AC constituents with aging in male and female normal rats.

Design

The glycosaminoglycan (GAG) and collagen (COL) contents of the AC in knee, hip, and shoulder joints of male and female rats were quantified and compared between age groups and sexes.

Results

The amount of GAG was decreased in multiple joints in both males and females with aging. In females, it had a significant decrease in all joints measured. The decrease in GAG with aging was more severe in females than in males. Even in young rats, the amount of knee joint GAG was significantly less in females than in males. The amount of COL in the AC was unchanged with aging in both sexes.

Conclusions

The drastic GAG decrease with aging in female normal rats may explain the higher prevalence and more severe OA in females.
The development of pevonedistat in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): hope or hype?
Authors: Snow Anson , Zeidner Joshua F.
Published: July 2022

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder clinically defined by cytopenias, bone marrow failure, and an increased risk of progressing to acute myeloid leukemia (AML). Traditionally, first-line treatment for patients with higher-risk MDS has been hypomethylating agents (HMAs). However, these agents have modest clinical activity as single agents. A one-size-fits-all treatment paradigm is insufficient for such a heterogeneous disease in the modern era of precision medicine. Several new agents have been developed for MDS with the hopes of improving clinical outcomes and survival. Pevonedistat is a first-in-class, novel inhibitor of neuronal precursor cell-expressed developmentally down-regulated protein-8 (NEDD8) activating enzyme (NAE) blocking the neddylation pathway leading to downstream effects on the ubiquitin–proteosome pathway. Pevonedistat ultimately leads to apoptosis and inhibition of the cell cycle in cancer cells. Studies have demonstrated the safety profile of pevonedistat, leading to the development of multiple trials investigating combination strategies with pevonedistat in MDS and AML. In this review, we summarize the preclinical and clinical rationale for pevonedistat in MDS and AML, review the clinical data of this agent alone and in combination with HMAs to date, and highlight potential future directions for this agent in myeloid malignancies.
Instant messaging client gives the opportunity to recognize gut microbiota and dysbiosis-related disease: An investigation study on WeChat APP
Authors: Liu Yujie , Zhang Sheng , Wu Xia , Li Qianqian , Wang Yun , Huang Yihao , Zhang Faming , Cui Bota , Lu Xiang
Published: July 2022

Objectives

Gut microbiota and dysbiosis are closely related to the occurrence and development of various diseases. It is necessary to popularize gut microbiota-related knowledge to the public. And the instant messaging client on smartphones supplies a perfect tool to achieve this goal. Hence, we will describe the current status of gut microbiota education spread by WeChat official accounts.

Methods

The keywords of “gut microbiota,” “fecal microbiota transplantation (FMT),” and “probiotics” were searched in the articles published from January 2015 to August 2020 on the WeChat official accounts. And the data were analyzed based on the 10 common gut dysbiosis-related diseases.

Results

A total of 3061 WeChat official accounts have published 11,239 articles on gut microbiota dysbiosis-related diseases, with a rising trend in the total article numbers and the total pageviews. The keywords of “gut microbiota” dominate 50.61%, and the articles on inflammatory bowel disease had the largest proportion. Additionally, articles on the keyword “gut microbiota” also included cancer and obesity, articles on the keyword “FMT” mainly consist of Clostridium difficile infection and psychological disease, and the keyword “probiotics” was mainly related to obesity and irritable bowel syndrome disease. The top three total pageviews were on inflammatory bowel disease, obesity, and cancer.

Conclusion

This study indicates the current research hotspots and public concerns on the gut microbiota, and WeChat as an instant messaging client plays an important role in promoting the scientific popularization of gut microbiota.
The Political Consequences of Online Disagreement: The Filtering of Communication Networks in a Polarized Political Context
Authors: Zhang Xinzhi , Lin Wan-Ying , Dutton William H.
Published: July 2022

The present study challenges prevailing beliefs and research on the role of social media in supporting deliberation and an active public sphere. Based on a two-wave online panel survey ( n = 791) of the adult population of Hong Kong, as one case of a politically polarized society, we examine the degree to which individuals disconnect from those with whom they politically disagree with on social media. The analysis indicates that exposure to disagreement does indeed lead people to filter their information repertoire by disconnecting from those with whom they disagree. A moderated mediation analysis finds that political disagreement indirectly influenced activist participation through information repertoire filtration. However, in contrast to expectations, this effect was stronger when individuals had a lower level of affective polarization. Our findings underscore the value of focusing on the behavior of users to complement research on access to information about politics.
Acute Liver Failure due to Altered Fontan Circulation in a Patient With Tricuspid Atresia: A Case Report
Authors: Mikhail Jason , Tavakolian Kameron , Odak Mihir , Nightingale Romany , Douedi Steven , Elkherpitawy Islam
Published: July 2022

Tricuspid atresia is a congenital malformation of the tricuspid valve resulting in a lack of blood flow between the right atrium and the right ventricle. Management generally involves staged surgical intervention enabling affected individuals to survive into adulthood. Although surgical intervention greatly improves morbidity and mortality in this patient population, there are many long-term complications associated with the creation of a surgical shunt. We report a case of a 33-year-old male with tricuspid atresia who underwent Fontan surgery as a child and presented to our hospital with acute liver failure.
Concussions in the Women’s National Basketball Association: Analysis of Incidence, Return-to-Play Timing, and Player Performance From 1997 to 2020
Authors: Walker Jasmine , Marigi Erick M. , Dancy Malik , Okoroha Kelechi R. , Kharrazi F. Daniel , Mehran Nima
Published: July 2022

Background:

The extent to which concussions affect Women’s National Basketball Association (WNBA) athletes has not been thoroughly examined.

Purpose:

To evaluate the incidence and impact of concussion injuries occurring in the WNBA.

Study Design:

Descriptive epidemiology study.

Methods:

Publicly available records were searched to identify all documented basketball-related concussions from WNBA seasons 1997 to 2020. Player demographics, injury details, and basketball career information were collected. Concussion incidence and return-to-play (RTP) timing were evaluated before and after the institution of the WNBA concussion protocol in 2012. Minutes per game and game score per minute were compared 5 games before and 5 games after the concussion was sustained. Player game availability and RTP performance were also compared with an age-, body mass index–, position-, and experience-matched control group of players who did not sustain any injuries during the index season.

Results:

A total of 70 concussions among 55 players were reported in the WNBA from 1997 to 2020, with a mean incidence of 2.9 ± 2.3 concussions per season. After the implementation of the WNBA concussion protocol, the incidence significantly increased from 1.7 to 5.0 concussions per season ( P < .001). All players returned after a first-time concussion, missing a mean of 3.8 ± 4.7 games and 17.9 ± 20.7 days. After the adoption of the concussion protocol, the time to RTP significantly increased with games missed ( P = .006) and days missed ( P = .006). Minutes per game and game score per minute were not significantly affected by sustaining a concussion ( P = .451 and P = .826, respectively).

Conclusion:

Since the adoption of the WNBA concussion protocol in the 2012 season, the incidence of concussions increased significantly. Athletes retained a high rate of RTP after missing a median of 4 games, and the time to RTP increased after the institution of the concussion protocol. Player game availability and performance within the same season were not significantly affected by concussion injuries after a successful RTP.