bluuebunny/crossref_metadata_2025 huggingface dataset:
Mood Disorders and Anxiety in Parkinson’s Disease: Current Concepts
Authors: Lintel Hendrik , Corpuz Timothy , Paracha Saif-ur-Rahman , Grossberg George T.
Published: July 2021

Mood disorders and anxiety significantly impact the prognosis and disease course of Parkinson’s disease. Non-motor symptoms of Parkinson’s disease such as apathy, anhedonia, and fatigue overlap with diagnostic criteria for anxiety and depression, thus making accurate diagnosis of mood disorders in Parkinson’s disease patients difficult. Furthermore, treatment options for mood disorders can produce motor complications leading to poor adherence and impaired quality of life in Parkinson’s disease patients. This review aims to clarify the current state of diagnostic and treatment options pertaining to anxiety and mood disorders in Parkinson’s disease. It explores both the pharmacologic and non-pharmacologic treatment modalities for various mood disorders in comorbid Parkinson’s disease with a brief discussion of the future outlook of the field given the current state of the literature.
Psychosis in Parkinson’s Disease: Current Treatment Options and Impact on Patients and Caregivers
Authors: Segal Gilad S. , Xie Sophie J. , Paracha Saif-ur-Rahman , Grossberg George T.
Published: July 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disease seen in older adults after Alzheimer’s disease, with increasing prevalence worldwide. Parkinson’s disease psychosis (PDP) is a common, non-motor feature of PD, which increases caregiver stress and is a risk-factor for nursing home placement. In this paper we review PDP epidemiology, features, diagnosis, and treatment. PDP most often presents with sequential development of minor and then increasingly complex visual hallucinations mediated by dopaminergic-serotonergic interactions activating the mesolimbic pathway, with contributions from other structures and neurotransmitters. Appropriate evaluation of differential diagnoses for psychosis is vital before diagnosing PDP. Initial treatment should involve non-pharmacologic approaches. If these are unsuccessful and PDP symptoms significantly impact the patient’s and or their caregivers’ quality of life and functions, then pharmacotherapy is indicated. Pimavanserin is a recently FDA-approved pharmacologic treatment for PDP with a better profile of balanced effectiveness and safety compared to previous use of atypical antipsychotics. Early diagnosis and safer, more effective treatments for PDP should help reduce caregiver burden and enable caregivers to continue to provide care at home versus institutionalization.
Effect of macro and molecular initiators on the structure-property relationship of poly(ε-caprolactone)
Authors: Thamizhlarasan A , Meenarathi B , Anbarasan R
Published: July 2021

Ring opening polymerization (ROP) of ε-caprolactone (CL) was carried out by bulk polymerization technique using stannous octoate (SO) as a catalyst and in the presence of macro or molecular initiator for 5 h under inert atmosphere with mild stirring. The % yield of poly(ε-caprolactone) (PCL) obtained was calculated and compared based on the chemical structure of macro and molecular initiators. Various analytical techniques such as FT-IR, 1H-NMR, XPS, GPC, DSC, TGA, SEM and WCA were used to characterize the PCL. The FT-IR spectrum showed the C=O stretching around ∼1725 cm−1. The aromatic proton signal of isoeugenol (IE) initiator appeared at 7–8 ppm in the proton NMR spectrum. The experimental results obtained were compared with the literature values.
Robust adaptive tracking control for uncertain nonholonomic mobile manipulator
Authors: Brahmi Abdelkrim , Saad Maarouf , Brahmi Brahim , Bojairami Ibrahim El , Gauthier Guy , Ghommam Jawhar
Published: July 2021

In the research put forth, a robust adaptive control method for a nonholonomic mobile manipulator robot, with unknown inertia parameters and disturbances, was proposed. First, the description of the robot’s dynamics model was developed. Thereafter, a novel adaptive sliding mode control was designed, to which all parameters describing involved uncertainties and disturbances were estimated by the adaptive update technique. The proposed control ensures a relatively good system tracking, with all errors converging to zero. Unlike conventional sliding mode controls, the suggested is able to achieve superb performance, without resulting in any chattering problems, along with an extremely fast system trajectories convergence time to equilibrium. The aforementioned characteristics were attainable upon using an innovative reaching law based on potential functions. Furthermore, the Lyapunov approach was used to design the control law and to conduct a global stability analysis. Finally, experimental results and comparative study collected via a 05-DoF mobile manipulator robot, to track a given trajectory, showing the superior efficiency of the proposed control law.
Electrohydraulic proportional valve-controlled vane type semi-rotary actuated wind turbine control by feedforward fractional-order feedback controller
Authors: Venkaiah Paladugu , Sarkar Bikash Kumar
Published: July 2021

In this study, proportional valve-controlled semi-rotary electrohydraulic actuator proposed for horizontal axis wind turbine pitch movement. Semi-rotary actuator can be connected directly to the wind turbine blade, which reduces mechanical complexity compare to linear electrohydraulic actuator system. Adaptive torque control scheme has been adopted for the horizontal axis wind turbine in region II; however, adaptive pitch control has been adopted for region III. Optimum pitch demand and torque demand have been estimated through blade element momentum theory based on predicted wind speed. The control objective is to track maximum power through torque control in region II and to maintain rated power with structural safety by limiting thrust force in the region III. The proposed wind turbine model has been validated with 1.5-MW wind turbine experimental data. Feedforward fractional-order proportional–integral–derivative controller with adaptive teaching–learning based optimization algorithm has been developed for wind turbine control application. In region II, feedforward control signal generates due to torque demand and feedback control signal generates due to combined torque and pitch error. However, in region III, feedforward and feedback control estimated with pitch demand and combined pitch and torque error, respectively. The proposed controller performance has been tested with sinusoidal, step and actual wind data. The controller performance also compared with respect to other conventional controllers. Performance of the adaptive teaching–learning-based optimization has been compared with genetic algorithm and teaching–learning-based optimization process. Sensitivity analysis has been performed with proposed controller to check the effectiveness of the optimization. Furthermore, the proposed controller response has been compared with existing data of 1.5-MW wind turbine. Lyapunov-based stability analysis has been performed to ensure stability and convergence of the proposed system. Proposed controller performance has been found better compare to the existing result.
Taraxasterol inhibits TGF-β1-induced epithelial-to-mesenchymal transition in papillary thyroid cancer cells through regulating the Wnt/β-catenin signaling
Authors: Zhu J , Li X , Zhang S , Liu J , Yao X , Zhao Q , Kou B , Han P , Wang X , Bai Y , Zheng Z , Xu C
Published: July 2021

Taraxasterol (TAR) is a kind of active compound extracted from dandelion and its molecular structure resembles steroid hormones. Recently, TAR has been reported to show an anti-tumor activity. However, the specific role of TAR in papillary thyroid cancer (PTC) has not been clarified. In this study, we investigated the effect of TAR on PTC cell migration, invasion and epithelial-to-mesenchymal transition (EMT) induced by TGF-β1. PTC cells were exposed to TGF-β1 (5 ng/mL) and then treated with different concentrations of TAR. We found that TAR showed no obvious cytotoxicity below 10 μg/mL but notably reduced migration and invasion of TGF-β1-treated PTC cells. Moreover, TAR treatment decreased MMP-2 and MMP-9 levels, and obviously affected the expression of EMT markers. We also observed that Wnt3a and β-catenin levels were significantly increased in TGF-β1-treated PTC cells while TAR inhibited these effects in a concentration-dependent manner. Additionally, activation of the Wnt pathway by LiCl attenuated the suppressive effect of TAR on TGF-β1-induced migration, invasion and EMT in PTC cells. Taken together, we highlighted that TAR could significantly suppress TGF-β1-regulated migration and invasion by reversing the EMT process via the Wnt/β-catenin pathway, suggesting that TAR may be a potential anti-cancer agent for PTC treatment.
Career Success of Women: Role of Family Responsibilities, Mentoring, and Perceived Organizational Support
Authors: Chauhan Jyoti , Mishra Geeta , Bhakri Suman
Published: July 2021

Women are under-represented at top-level positions despite increasing women empowerment and participation, and decelerating gender discrimination in India. Women must go through various obstacles in order to reach to senior- or top-level positions in their professional life. Since there are many impediments that a woman must overcome to get career success, however, this study focuses on the impediments that women face due to organizational and family impediment. The current research article aims to evaluate whether lack of mentoring, perceived organizational support (POS), and family responsibilities impact the perceived career success (PCS) of women in the Indian Information Technology (IT) sector. Data in this regard have been collected using a structured questionnaire and a total of 292 respondents have been analysed. In order to examine the impact of these impediments on the perceived career success of women, the method of structural equation modelling (SEM), has been used. Findings of the study reveal that each of the independent variables significantly impacts the perceived career success of women which works as a wake-up call for women executives that they must overcome these impediments to advance their career smoothly.
Development of gates to measure the immature platelet fraction in C57BL/6J mice using the Sysmex XN-V series multispecies hematology analyzer
Authors: Davenport Patricia , Lorenz Viola , Liu Zhi-Jian , Feldman Henry A. , Canas Jorge , Nolton Emily , Badur Chiara-Aiyleen , Do Thi Minh-Thi , Sola-Visner Martha
Published: July 2021

The immature platelet fraction (IPF) is a measure of newly released platelets, which has been used as a marker of platelet production in multiple human studies but is not widely available in multispecies analyzers. We developed gates to measure the IPF in diluted and undiluted murine blood samples on the Sysmex XN-1000V multispecies hematology analyzer. IPF gates were created using undiluted and diluted (1/10) blood samples obtained from adult and newborn (postnatal day 10, P10) C57BL/6J wild-type (WT) mice, and from 3 murine models of thrombocytopenia: c-MPL−/− mice, which lack the thrombopoietin receptor (hyporegenerative); antibody-mediated thrombocytopenia; and acute inflammation-induced thrombocytopenia. P10 mice were chosen because, at their size, we could consistently obtain (by terminal phlebotomy) the blood volume needed to run an undiluted sample. The undiluted blood IPF gate successfully differentiated between mechanisms of thrombocytopenia in both adult and P10 mice. For diluted samples, 2 IPF gates were generated: a thrombocytopenic (T) gate, which performed well in samples with platelet counts (PCs) <800 × 109/L in adult mice and <500 × 109/L in newborn mice, and a non-thrombocytopenic (NT) gate, which performed well in samples with PCs above these thresholds. PCs and IPFs measured in diluted blood using these gates agreed well with those measured in undiluted blood and had good reproducibility. These diluted gates allow for the accurate measurement of PCs and IPFs in small (10 µL) blood volumes, which can be obtained easily from adult and newborn mice as small as P1 to assess platelet production serially.
Supported Decision-Making in Criminal Proceedings: A Sociolegal Empirical Study
Authors: Gooding Piers , McSherry Bernadette , Arstein-Kerslake Anna
Published: July 2021

This article outlines a project in which supported decision-making (SDM) and broader support to exercise legal capacity were provided to accused persons with cognitive disabilities in the Australian criminal justice system. The program was developed to advance the United Nations Convention on the Rights of Persons with Disabilities (CRPD) in relation to “unfitness to plead” laws. The researchers collaborated with three community legal services in three Australian jurisdictions. Four nonlegal “disability support people” were trained to work with accused persons alongside legal counsel to maximize their participation in the trial process and avoid the need for unfitness to plead determinations under current laws. The article draws on qualitative research conducted in the form of interviews with clients, lawyers, and support persons. The findings provide an evidence base for implementing SDM for persons with disabilities in the criminal justice system. It also helps answer the question of whether unfitness to plead laws should be repealed in pursuit of a “universally accessible” justice system in line with the CRPD.
Time to Fix the Damage of Weakened Chemical Disaster Prevention Regulations
Authors: Moure-Eraso Rafael
Published: July 2021

The Trump administration weakened regulations through changes on rules that have been improved during the Obama years. An example is the reversal in 2019 of the improvements to the U.S. Environmental Protection Agency Risk Management Program, Chemical Disaster Prevention Rule. In 2013 a catastrophic explosion of ammonium nitrate in West, Texas, provided the impetus to improve the original regulations after an investigation of its consequences. The justification for reversing the improvements was provided by one of the three federal investigations conducted by the U.S. Bureau of Alcohol, Tobacco, Firearms and Explosives which alleged, without proof, that the West, Texas explosion was caused by arson and thus nonpreventable. This commentary reviews the details of this reversal and recommends that the U.S. Environmental Protection Agency, now under the Biden Administration, resurrect its 2016 Risk Management Program chemical disaster rule in order to prevent future chemical facility catastrophes.
Child Welfare System Involvement Among Children With Medical Complexity
Authors: Azzopardi Corry , Cohen Eyal , Pépin Karine , Netten Kathy , Birken Catherine , Madigan Sheri
Published: July 2021

Children with medical complexity may be at elevated risk of experiencing child maltreatment and child welfare system involvement, though empirical data are limited. This study examined the extent of child welfare system involvement among children with medical complexity and investigated associated health and social factors. A retrospective chart review of children with medical complexity (N = 208) followed at a pediatric hospital-based complex care program in Canada was conducted. Descriptive statistics and odds ratios using logistic regression were computed. Results showed that nearly one-quarter (23.6%) had documented contact with the child welfare system, most commonly for neglect; of those, more than one-third (38.8%) were placed in care. Caregiver reported history of mental health problems (aOR = 3.19, 95%CI = 1.55–6.56), chronic medical conditions (aOR = 2.86, 95%CI = 1.09–7.47), and interpersonal violence or trauma (aOR = 17.58, 95%CI = 5.43–56.98) were associated with increased likelihood of child welfare system involvement, while caregiver married/common-law relationship status (aOR = 0.35, 95%CI = 0.16–0.74) and higher number of medical technology supports (aOR = 0.75, 95%CI = 0.57–0.99) were associated with decreased likelihood. Implications for intervention and prevention of maltreatment in children with high healthcare needs are discussed.
Service Research Priorities: Managing and Delivering Service in Turbulent Times
Authors: Ostrom Amy L. , Field Joy M. , Fotheringham Darima , Subramony Mahesh , Gustafsson Anders , Lemon Katherine N. , Huang Ming-Hui , McColl-Kennedy Janet R.
Published: July 2021

Transformative changes in the societal and service context call out for the service discipline to develop a coherent set of priorities for research and practice. To this end, we utilized multiple data sources: surveys of service scholars and practitioners, web scraping of online documents, a review of published service scholarship, and roundtable discussions conducted at the world’s foremost service research centers. We incorporated innovative methodologies, including machine learning, natural language processing, and qualitative analyses, to identify key service research priorities that are critical to address during these turbulent times. The first two priorities— technology and the changing nature of work and technology and the customer experience—focus on leveraging technology for service provision and consumption. The next two priorities— resource and capability constraints and customer proactivity for well-being—focus on responding to the changing needs of multiple stakeholders. Further, we identified a set of stakeholder-wants from the literature and include research questions that tie key stakeholder-wants to each of the four priorities. We believe the set of research priorities in the present article offer actionable ideas for service research directions in this challenging environment.
A quasi-three-dimensional isogeometric model for porous sandwich functionally graded plates reinforced with graphene nanoplatelets
Authors: Nguyen Nam V , Nguyen-Xuan H , Lee Jaehong
Published: July 2021

The purpose of this study is to present a quasi-three-dimensional (quasi-3D) shear deformation theory for static bending and free vibration analyses of porous sandwich functionally graded (FG) plates with graphene nanoplatelets (GPLs) reinforcement. In addition, we propose a novel sandwich plate model with various outstanding features in terms of structural performance. The quasi-3D theory-based isogeometric analysis (IGA) in conjunction with refined plate theory (RPT) is first exploited to capture adequately the thickness stretching effect for porous sandwich FG plate structures reinforced with GPLs. The Non-Uniform Rational B-Splines (NURBS)-based IGA is employed in order to describe exactly the geometry models as well as approximate the unknown field with higher-order derivatives and continuity requirements while the RPT model includes only four essential variables. The sandwich FG plates consist of a core layer containing internal pores reinforced by GPLs and two functionally graded materials (FGMs) skin layers. Effective mechanical properties can be evaluated by employing the Halpin-Tsai model along with the rule of mixture. Various combinations of two porosity distributions and three GPL dispersions in the core layer are thoroughly investigated. Several numerical investigations are conducted to examine the effects of several key parameters on the static bending and free vibration behaviors of sandwich FG plate structures.
Morphosyntactic inconsistency in cross-linguistic transfer: Pedagogical implications for teaching English questions to Chinese EFL learners
Authors: He Qiaoling , Oltra-Massuet Isabel
Published: July 2021

As one type of the most extensively used sentences, English questions are must-learn grammatical structures for learners of English as a foreign language (EFL). However, it is commonly seen that English learners across proficiency levels produce ungrammatical English questions. To determine the source of learners’ erroneous production, we conducted a written test to collect hands-on data of four types of English questions produced by 81 Chinese EFL preliminary learners. Learners’ achievement scores showed that learners from both higher and lower proficiency groups had similar difficulty producing questions. The statistics also showed morphosyntactic inconsistencies in learners’ production were congregating on auxiliaries’ choice and tense variation. Cross-linguistic transfer from first language (L1) in English question acquisition for Chinese EFL learners was measured against the three dimensions of Jarvis’ (2000) methodological model. Influence from learners’ L1 was found to be related to preliminary learners’ morphosyntactic inconsistencies. The findings suggest that practitioners in an EFL context should raise learners’ grammatical consciousness, and design production-oriented tasks, to improve learners’ morphosyntactic accuracy in English question formation.
Asthma patients experience increased symptoms of anxiety, depression and fear during the COVID-19 pandemic
Authors: de Boer Geertje M , Houweling Laura , Hendriks Rudi W , Vercoulen Jan H , Tramper-Stranders Gerdien A , Braunstahl Gert-Jan
Published: July 2021

Population studies showed a decrease in psychological wellbeing during the COVID-19 pandemic. Asthma is associated with a negative effect on anxiety and depression, which might worsen during the COVID-19 lockdown. The aim of the study was to compare fear, anxiety and depression between asthma patients and patients wit hout asthma pre-COVID-19 and during COVID-19 pandemic.

This study compares fear, anxiety and depression in asthma patients and controls between pre-COVID-19 and during COVID-19 lockdown with a cross-sectional online survey. Participants were invited to fill out several questionnaires pertaining to fear, anxiety, depression, asthma control and quality of life.

Asthma patients (N = 37) displayed, during the course of the pandemic, a clinically relevant increase in anxiety (3.32 ± 2.95 vs. 6.68 ± 3.78; p < 0.001) and depression (1.30 ± 1.15 vs. 3.65 ± 3.31; p < 0.001), according to the hospital anxiety and depression levels (HADS) compared to pre-COVID-19 assessment. This was not seen in controls. Also, asthma patients displayed more anxiety about acquiring COVID-19 disease compared to controls ((5.11 ± 1.99 vs. 3.50 ± 2.79), p = 0.006).

Patients with asthma experienced an increase in anxiety and depression levels and were more afraid of acquiring COVID-19 disease compared to controls. Also, patients with asthma were more likely to avoid healthcare facilities due to fear of acquiring COVID-19 disease compared to controls. Therefore, we advise health care workers to address these possible negative effects on mental health by phone or e-consults.
Chronic Painless, Multiple Papulo-Nodular Skin Lesion at Foot Resembles Mycetoma Infection (Madura Foot): A Case Report
Authors: Bahar Moni Ahmed Suparno , Hoque Md M.
Published: July 2021

Madura foot is a chronic, progressively destructive bacterial or fungal infection of the subcutaneous tissues, which may affect skin, muscle, and bone. It is endemic in tropical and subtropical areas known as the “Mycetoma belt” between latitude 30°N and 15°S. Mycetoma is prevalent in the poor population living in remote areas of developing countries that lack proper reporting system and management. The World Health Organization recognized mycetoma as a neglected tropical disease back in 2016. Though the diagnosis is challenging, early detection and proper treatment can reduce morbidity and provide a promising outcome. We report a case of chronic painless, multiple papulo-nodular skin lesions at the foot that resembles mycetoma infection which was detected early and recovered with a satisfactory outcome with proper treatment.
Comparison of generic drug registration strategies between health Canada and Gulf Cooperation Council
Authors: Charyulu Narayana R , Narayanan Anoop V , Shetty Amitha
Published: July 2021

Recently, generic drug products have played an increasingly important role in the health care system globally, especially in the developing world, as they provide for an effective and more affordable alternative for healthcare professional. Generic drug products are proven therapeutically equivalent to the corresponding innovator’s product, and hence can be substituted in clinical practice. The Gulf Cooperation Council’s pharmaceutical market is known to be semi-regulated market when compared with Health Canada and the United States of America drug regulatory market. Product regulation in Gulf Cooperation Council and Health Canada are challenging task in comparison to EU and USA. This study aimed to understand the generic drug registration comparison of Health Canada and Gulf Cooperation Council’s. The aim of this study was achieved by review of the Health Canada and Gulf Cooperation council guidelines and publications. Health Canada and Gulf Cooperation council follows Common Technical Document format and also emphasizes on safety, quality and efficacy of the drug. In summary Gulf Cooperation council and Health Canada offers lucrative market for Indian pharmaceutical manufacturer and the process of registration has been simplified by centralized procedure.
A systematic review of training methods to increase staff’s knowledge and implementation of positive behaviour support in residential and day settings for individuals with intellectual and developmental disabilities
Authors: Mahon Dearbaile , Walsh Edith , Holloway Jennifer , Lydon Helena
Published: July 2021

Behaviour support plans (BSPs), if accurately implemented, have been found to increase skills and decrease challenging behaviour of individuals with intellectual and developmental disabilities. Training is essential for staff to acquire the skills necessary for accurate implementation. The aim of this systematic literature review was to evaluate procedures used to train staff in Positive Behaviour Support (PBS), on both knowledge of PBS and implementation of BSPs. Systematic searches of 4 databases identified 18 studies as meeting criteria. Findings indicate that description alone was not consistently effective in increasing knowledge and should be used in combination with other training strategies. Staff’s implementation of BSPs were increased by different combinations of the following training components: description, feedback, modelling, role-play, monitory incentive, and escape contingency. To identify evidenced based practice when training staff on BSPs, it is necessary to evaluate active and feasible training components from current training models.
A new warranty policy for heterogeneous items subject to monotone degradation processes
Authors: Cha Ji Hwan , Finkelstein Maxim
Published: July 2021

A new renewable warranty policy is suggested that increases the probability of its success and can decrease the corresponding costs for certain ranges of parameters. It deals with heterogeneous populations of items from two subpopulations (‘weak’ and ‘strong’) and is aimed at elimination and further replacement of weak items after screening at some optimal time. This elimination is performed when degradation described by the corresponding mixed degradation process reaches some optimally predetermined level. Probabilistic and cost analyses of the model are performed and the illustrative example is presented. It is shown that the proposed warranty policy with inspection outperforms the conventional one in a probabilistic sense. Furthermore, the proposed policy becomes economically beneficial especially when the additional penalty cost caused by a sudden failure is large.
How It Started, How It Is Going: The Future of Artificial Pancreas Systems (Automated Insulin Delivery Systems)
Authors: Lewis Dana
Published: July 2021

Originally, the future of automated insulin delivery (AID) systems, or artificial pancreas systems (APS), was having them at all, in any form. We’ve learned in the last half dozen years that the future of all artificial pancreas systems holds higher time in range, less work required to manage automated insulin delivery systems to improve quality of life, and the ability to input critical information back into the system itself. The data and user experience stories make it clear: APS works. APS are an improvement over other diabetes therapy methods when they are made available, accessible, and affordable. Understanding the unmet expectations of current users of first generation APS technology may also aid in the development of improved technology and user experiences for the future of APS.
Anger and Sadness as Moral Signals
Authors: Plaks Jason E. , Robinson Jeffrey S. , Forbes Rachel
Published: July 2021

Three studies examined the relationship between emotions and moral judgment from an interpersonal perspective. In Studies 1 and 2, participants justified their decisions in sacrificial dilemmas to an imagined interlocutor. Linguistic analyses revealed that Don’t Sacrifice justifications contained more anger-related language than sadness-related language, whereas Sacrifice justifications contained roughly equal proportions of anger and sadness language. In Study 3, participants made character inferences about an actor who chose to/refused to sacrifice one person to save multiple people. We manipulated the actor’s ratio of anger to sadness. Participants rated the Don’t Sacrifice actor more negatively when they displayed high anger relative to sadness but rated the Sacrifice actor negatively whenever they exhibited high anger (independent of sadness). These data highlight novel ways in which actors and observers use emotions to complement the substance of a moral argument.
Delayed leukoencephalopathy from suspected polymer embolism after neuroendovascular procedures
Authors: Mellemkjær Thomas , Chandra Ronil V , Speiser Lasse , Ulhøi Benedicte P , Simonsen Claus Z
Published: July 2021

As the neurointervention field grows, a new side effect emerges. Delayed leukoencephalopathy (DL) is believed to be an inflammatory or allergic reaction to polymer material that is shed from catheters during endovascular procedures. We present four cases of DL after aneurysm treatment in two patients, endovascular stroke treatment and diagnostic arteriography. We present our diagnostic process, including biopsy results in two patients, our anti-inflammatory treatment and outcomes together with a review of the literature. In our series, prognosis was variable with ongoing seizures in two patients. Our literature review reveals that asymptomatic shedding of polymer material is common, occurring in a third of endovascular stroke procedures, whereas symptomatic DL occurs in <0.5% of therapeutic neuroendovascular procedures. Clinicians should be aware of this rare complication, and oral glucocorticoids seem to be a reasonable first-line treatment strategy.
Cervical Steroid Injections Are Not Effective for Prevention of Surgical Treatment of Degenerative Cervical Myelopathy
Authors: Manzur Mustfa K. , Samuel Andre M. , Vaishnav Avani , Gang Catherine Himo , Sheha Evan D. , Qureshi Sheeraz A.
Published: July 2021

Study Design:

Retrospective cohort study.

Objective:

The objective of this study is to determine how often patients with degenerative cervical myelopathy (DCM) and initially treated with cervical steroid injections (CSI) and to determine whether these injections provide any benefit in delaying ultimate surgical treatment.

Methods:

All patients with a new diagnosis of DCM, without previous cervical spine surgery or steroid injections, were identified in PearlDiver, a large insurance database. Steroid injection and surgery timing was identified using Current Procedural Terminology (CPT) codes. Multivariate logistic regression identified associations with surgical treatment.

Results:

A total of 686 patients with DCM were identified. Pre-surgical cervical spine steroid injections were utilized in 244 patients (35.6%). All patients underwent eventual surgical treatment. Median time from initial DCM diagnosis to surgery was 75.5 days (mean 351.6 days; standard deviation 544.9 days). Cervical steroid injections were associated with higher odds of surgery within 1 year (compared to patients without injections, OR = 1.44, P < .001) and at each examined time point through 5 years (OR = 2.01, P < .001). In multivariate analysis comparing injection types, none of the 3 injection types were associated with decreased odds of surgery within 1 month of diagnosis.

Conclusions:

While cervical steroid injections continue to be commonly performed in patients with DCM, there is an overall increased odds of surgery after any type of cervical injection. Therefore injections should not be used to prevent surgical management of DCM.
Exploration into practical significance of integral water permeability of textile vascular grafts
Authors: Guan Guoping , Yu Chenglong , Fang Xuan , Guidoin Robert , King Martin W , Wang Hongjun , Wang Lu
Published: July 2021

Water permeability of textile vascular grafts has been considered as a key indicator for predicting blood permeability after implantation. However, a correlation between water and blood permeability has not been established yet. Therefore, even though the water permeability of a vascular graft can be tested according to the standard ISO 7198, the results fail to guide a manufacturer or a surgeon to judge whether this vascular graft needs pre-clotting or not prior to implantation. As a result, all commercial graft products show almost zero water permeability, which leads to the loss of advantages that textile vascular grafts have the pore size-controlled porous wall. To solve this problem, four types of woven vascular grafts were designed and manufactured in the present work. Then their permeability to water, simulated plasma, and anticoagulated whole blood were measured at graded pressures from 8 to 16 kPa. Moreover, the correlations among the water permeability, the simulated plasma permeability, and the anticoagulated whole blood permeability were established. The results suggest that relatively steady correlations exist between the water permeability and the anticoagulated whole blood permeability, and that the evaluation of the blood permeability using the water permeability is feasible and objective. The present work provides a quantitative method for evaluating the blood permeability using the water permeability, and the latter is thus endowed with practical significance for guiding designs and clinical pre-clotting operations of textiles vascular grafts.
Evaluating the Efficacy of Povidone-Iodine Solution Infection Prophylaxis in Immediate Tissue Expander-Based Breast Reconstruction: A Controlled Retrospective Analysis
Authors: Teotia Sumeet S. , Kadakia Yash , Amaya Joshua , Liu Yulun , Haddock Nicholas T.
Published: July 2021

Background: There is currently no consensus among plastic surgeons regarding the optimal infection prophylaxis for immediate tissue expander placement following mastectomy. The goal of this study was to determine whether irrigation with 1 L of standard triple antibiotic solution (TAS) can achieve similar infection rates compared to a regimen of 180 mL of TAS with povidone-iodine solution (Betadine) painted on the field immediately prior to the placement of the expander. Methods: The 2 regimens were compared via retrospective propensity matching of all patients of the 2 senior authors who underwent bilateral tissue expander placement immediately following mastectomy with one of 3 mastectomy surgeons from January 2013 to December 2019 (n = 281). Groups were controlled for mastectomy surgeon, mastectomy type, mastectomy weight, age, race, body mass index, diabetes, hypertension, smoking, smoking status, prepectoral/subpectoral placement, use of acellular dermal matrix, operating room time, and duration of postoperative antibiotics. Results: Compared to the Betadine cohort (n = 65), the non-Betadine cohort (n = 65) experienced a similar rate of infections (13.8% vs 12.3%, P = 1.00), including major injections requiring intravenous antibiotic treatment (10.8% vs 9.2%, P = 1.00), after propensity matching. Infections in the non-Betadine cohort did not grow different bacteria on culture, require different antibiotic coverage, or result in prolonged duration of average antibiotic therapy (12.0 days vs 19.3 days, P = .19). Rates of subsequent expander washout and exchange ( P = 1.00) and overall complications that required return to the operating room ( P = .826) were similar between groups. Conclusion: The addition of Betadine solution to TAS added no benefit to infection prophylaxis or reduction of surgical complications in immediate tissue expander placement procedures.
An Early Detection Circuit for Endurance Enhancement of Backfilled Contact Resistive Random Access Memory Array
Authors: Kao Yun-Feng , Shih Jiaw-Ren , Lin Chrong Jung , King Ya-Chin
Published: July 2021

As one of the most promising embedded non-volatile storage solutions for advanced CMOS modules, resistive random access memory’s (RRAM) applications depend highly on its cyclability. Through detailed analysis, links have been found between noise types, filament configurations and the occurrence of reset failure during cycling test. In addition, a recovery treatment is demonstrated to restore the cyclability of RRAM. An early detection circuit for vulnerable cells in an array is also proposed for further improving the overall endurance of an RRAM array. Lifetime of RRAM can be extended to over 10 k cycles without fail bits in an array.
Bayesian updating: increasing sample size during the course of a study
Authors: Moerbeek Mirjam
Published: July 2021

Background

A priori sample size calculation requires an a priori estimate of the size of the effect. An incorrect estimate may result in a sample size that is too low to detect effects or that is unnecessarily high. An alternative to a priori sample size calculation is Bayesian updating, a procedure that allows increasing sample size during the course of a study until sufficient support for a hypothesis is achieved. This procedure does not require and a priori estimate of the effect size. This paper introduces Bayesian updating to researchers in the biomedical field and presents a simulation study that gives insight in sample sizes that may be expected for two-group comparisons.

Methods

Bayesian updating uses the Bayes factor, which quantifies the degree of support for a hypothesis versus another one given the data. It can be re-calculated each time new subjects are added, without the need to correct for multiple interim analyses. A simulation study was conducted to study what sample size may be expected and how large the error rate is, that is, how often the Bayes factor shows most support for the hypothesis that was not used to generate the data.

Results

The results of the simulation study are presented in a Shiny app and summarized in this paper. Lower sample size is expected when the effect size is larger and the required degree of support is lower. However, larger error rates may be observed when a low degree of support is required and/or when the sample size at the start of the study is small. Furthermore, it may occur sufficient support for neither hypothesis is achieved when the sample size is bounded by a maximum.

Conclusions

Bayesian updating is a useful alternative to a priori sample size calculation, especially so in studies where additional subjects can be recruited easily and data become available in a limited amount of time. The results of the simulation study show how large a sample size can be expected and how large the error rate is.
Severe restless legs syndrome in a family with Alport syndrome
Authors: Sparasci Davide , Rossinelli Andrea , Ferri Raffaele , Cippà Pietro , Rinaldi Andrea , Manconi Mauro
Published: July 2021

Background

Restless legs syndrome (RLS) is a common sleep-related movement disorder characterized by an urge to move the legs during inactivity, especially at evening-night. RLS is highly prevalent in patients with kidney failure and have an impact on quality of life, mood, sleep quality and overall on compliance to the dialysis. Alport syndrome (AS) is a rare inherited disease, predominantly X-linked, secondary to mutations in genes encoding α3, α4 or α5 chains of type IV collagen, and characterized by hematuria, chronic kidney disease, neurosensory deafness, and lenticonus.

Case presentation

Here we describe a family with a combination of X-linked AS and severe RLS accompanied by periodic limb movements during sleep (PLMS). In the first patient we identified, RLS was complicated by a paradoxical response to dopamine agonists named “augmentation”, leading to sleep disruption, hallucinations and five peritoneal perforations during the peritoneal dialysis due to the difficulty to rest still. Therapeutic adjustments and renal transplantation improved RLS and PLMS. In two brothers, severe RLS prevented a compliance with hemodialysis. Female family members carrying the mutation were also affected by RLS, while those without the mutations were RLS-free.

Conclusions

RLS has not been reported earlier in association with AS, but the peculiar combinations observed in this family will stimulate further clinical studies and motivate nephrologists to seek for RLS symptoms and sleep disturbances in AS patients.
A Japanese case of oculopharyngeal muscular dystrophy (OPMD) with PABPN1 c.35G > C; p.Gly12Ala point mutation
Authors: Nishii Yo-suke , Noto Yu-ichi , Yasuda Rei , Kitaoji Takamasa , Ashida Shinji , Tanaka Eijirou , Minami Narihiro , Nishino Ichizo , Mizuno Toshiki
Published: July 2021

Background

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy characterised by slowly progressive ptosis, dysphagia, and proximal limb muscle weakness. A common cause of OPMD is the short expansion of a GCG or GCA trinucleotide repeat in PABPN1 gene.

Case presentation

A 78-year-old woman presented with ptosis and gradually progressive dysphagia. Her son had the same symptoms. A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. Needle-electromyography (EMG) of bulbar and facial muscles revealed a myopathic pattern. Based on the characteristic muscle involvement pattern and needle-EMG findings, we suspected that the patient had OPMD. Gene analysis revealed PABPN1 c.35G > C point mutation, which mimicked the effect of a common causative repeat expansion mutation of OPMD.

Conclusion

We herein describe the first reported Japanese case of OPMD with PABPN1 point mutation, suggesting that this mutation is causative in Asians as well as in Europeans, in whom it was originally reported.
Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer
Authors: Brock Kristian , Homer Victoria , Soul Gurjinder , Potter Claire , Chiuzan Cody , Lee Shing
Published: July 2021

Background

The overwhelming majority of dose-escalation clinical trials use methods that seek a maximum tolerable dose, including rule-based methods like the 3+3, and model-based methods like CRM and EWOC. These methods assume that the incidences of efficacy and toxicity always increase as dose is increased. This assumption is widely accepted with cytotoxic therapies. In recent decades, however, the search for novel cancer treatments has broadened, increasingly focusing on inhibitors and antibodies. The rationale that higher doses are always associated with superior efficacy is less clear for these types of therapies.

Methods

We extracted dose-level efficacy and toxicity outcomes from 115 manuscripts reporting dose-finding clinical trials in cancer between 2008 and 2014. We analysed the outcomes from each manuscript using flexible non-linear regression models to investigate the evidence supporting the monotonic efficacy and toxicity assumptions.

Results

We found that the monotonic toxicity assumption was well-supported across most treatment classes and disease areas. In contrast, we found very little evidence supporting the monotonic efficacy assumption.

Conclusions

Our conclusion is that dose-escalation trials routinely use methods whose assumptions are violated by the outcomes observed. As a consequence, dose-finding trials risk recommending unjustifiably high doses that may be harmful to patients. We recommend that trialists consider experimental designs that allow toxicity and efficacy outcomes to jointly determine the doses given to patients and recommended for further study.
Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study)
Authors: Azim Lumbini , Hindmarch Paul , Browne Georgiana , Chadwick Thomas , Clare Emily , Courtney Paul , Dixon Lyndsey , Duffelen Nichola , Fouweather Tony , Geddes John R. , Goudie Nicola , Harvey Sandy , Helter Timea , Holstein Eva-Maria , Martin Garry , Mawson Phil , McCaffery Jenny , Morriss Richard , Simon Judit , Smith Daniel , Stokes Paul R. A. , Walker Jenn , Weetman Chris , Wolstenhulme Faye , Young Allan H. , Watson Stuart , McAllister-Williams R. Hamish
Published: July 2021

Background

Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson’s Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed.

Methods

The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology – Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures.

Trial registration

ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939

Protocol Version: 04-FEB-2021, Version 9.0.