bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive-based sliding mode control for mitigating torsional vibration of drill string in the presence of input delay and external disturbance
Authors: Sadeghimehr Roya , Nikoofard Amirhossein , Khaki Sedigh Ali
Published: September 2020

Dealing with torsional vibrations and stick–slip oscillations of a drill string system is a challenging engineering task in the oil drilling process because of the harmful and costly consequences of such vibrations. In this article, the drill string system is modeled using a lumped-parameter model with four degrees of freedom, and the bit–rock contact is represented by a nonlinear function of a bit velocity. Also, tracking the desired velocity of a drill string system with known constant input delay is addressed in the presence of external disturbance and parameter uncertainties by applying the Smith predictor–based sliding mode control method. The performance of the smith predictor–based sliding mode control with input delay and disturbance in tracking the desired velocity and controlling the stick–slip oscillations is compared with the sliding mode control with/without input delay. The system output’s sensitivity to the delay parameter is also investigated, indicating how the bit velocity changes concerning the delay parameter. The proper choice of adaptation gain is determinative in the performance of the controller, and its impact is investigated. Moreover, the robustness of the smith predictor–based sliding mode control is shown by changing the weight on the bit parameter. Simulation results demonstrate the effectiveness of the proposed method.
Vibration suppression for large-scale flexible structures based on cable-driven parallel robots
Authors: Sun Haining , Tang Xiaoqiang , Hou Senhao , Wang Xiaoyu
Published: September 2020

Specific satellites with ultralong wings play a crucial role in many fields. However, external disturbance and self-rotation could result in undesired vibrations of the flexible wings, which affect the normal operation of the satellites. In severe cases, the satellites would be damaged. Therefore, it is imperative to conduct vibration suppression for these flexible structures. Utilizing fuzzy-proportional integral derivative control and deep reinforcement learning (DRL), two active control methods are proposed in this article to rapidly suppress the vibration of flexible structures with quite small controllable force based on a cable-driven parallel robot. Inspired by the output law of DRL, a new control method named Tang and Sun control is innovatively presented based on the Lyapunov theory. To verify the effectiveness of these three control methods, three groups of simulations with different initial disturbances are implemented for each method. Besides, to enhance the contrast, a passive pretightening scheme is also tested. First, the dynamic model of the cable-driven parallel robot which comprises four cables and a flexible structure is established using the finite element method. Then, the dynamic behavior of the model under the controllable cable force is analyzed by the Newmark-ß method. Finally, these control methods are implemented by numerical simulations to evaluate their performance, and the results are satisfactory, which validates the controllers’ ability to suppress vibrations.
Safety Assessment of Polyene Group as Used in Cosmetics
Authors: Burnett Christina L. , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Liebler Daniel C. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Gill Lillian J. , Heldreth Bart
Published: September 2020

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of polyenes, which are reported to function in cosmetics primarily as film formers and viscosity increasing agents. The Panel reviewed relevant data related to these ingredients, not inggaps in the available safety data for some of the polyenes in this safety assessment. The data available for many of the ingredients are sufficient and can be extrapolated to support the safety of the entire group because of the similarities in the chemical structures, chemical properties, use concentrations, and reported functions across the group. The Panel concluded that polyenes were safe in cosmetics in the present practices of use and concentration described in this safety assessment.
Phox2b Immunohistochemical Staining in Detecting Enteric Neural Crest Cells in Hirschsprung Disease
Authors: Alturkustani Murad , Shillingford Nick , Zhou Shengmei , Wang Larry , Warren Mikako
Published: September 2020

Background

It can be challenging to recognize undifferentiated/immature ganglion cells, especially single forms. Ganglion cells and glia are derived from enteric neural crest cells (ENCCs), a group of autonomic nervous system (ANS)-lineage neural crest progenitors that PHOX2B regulates. Phox2b is an excellent marker for neoplastic and non-neoplastic ANS cells (eg, peripheral neuroblastic tumors [pNTs]). We hypothesized that Phox2b immunohistochemical staining (IHC) would also be useful for detecting ENCCs.

Methods

Hematoxylin and eosin, calretinin IHC, and Phox2b IHC were reviewed on 21 pull-through specimens and on a cohort of 12 rectal biopsies.

Results

Phox2b IHC demonstrated nuclear positivity in all of the ganglion cells across the different phases of differentiation without background staining. The Phox2b result correlated with the morphological findings, calretinin IHC results, and diagnoses based on the routine diagnostic method. The intensity was uniformly strong in the undifferentiated/immature forms and became variable in the mature forms; this pattern was similar to that seen in pNTs.

Conclusion

Phox2b IHC was highly sensitive and specific for detecting ganglion cells. It worked especially well for immature ganglion cells, seen in premature neonates, and scattered single forms in transition zones. In basic research settings, Phox2b can be a useful marker for early differentiation of ENCCs.
Sociodemographic, Clinical, and Pathological Factors Influencing Outcomes in Locally Advanced Triple Negative Breast Cancer: A Brazilian Cohort
Authors: da Silva Jesse Lopes , de Paula Bruno Henrique Rala , Small Isabele Avila , Thuler Luiz Claudio Santos , de Melo Andréia Cristina
Published: September 2020

Objective:

To evaluate the association of sociodemographic, clinical, and pathological factors with response and survival in triple negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NACT).

Methods:

Clinical-pathological and sociodemographic data were obtained from medical records of 235 eligible women with TNBC diagnosed between 2010 and 2014 undergoing NACT and surgery at the Brazilian National Cancer Institute. They have been assessed for pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). Both univariate and multivariate Cox regression analyses were performed.

Results:

The median follow-up was 64.3 months. Most patients had advanced clinical stage (III: 85.1%; cT3/T4: 86.4%; cN1-3: 74.4%) and high-grade tumors (72.1%). Clinical staging (III vs II, adjusted hazard ratio [HR] = 2.95, P = .012) significantly influenced the pCR rate. Alcohol intake negatively influenced EFS (adjusted HR = 1.67, P = .006) and OS (adjusted HR = 1.89, P = .005). Women with pCR showed better EFS (crude HR = 0.15, P < .001) and OS (crude HR = 0.12, P < .001) compared with non-pCR. The ypT (<0.001) and ypN (<0.001) gradually influenced survival outcomes.

Conclusion:

Clinical stage III were associated with lower response rate and worse survival. Alcohol intake, pCR, and burden of post-NACT residual disease have shown considerable influence on survival outcomes.
Temporality lost: A feminist invitation to vertical writing that shakes the ground
Authors: Helin Jenny
Published: September 2020

Are we, as academics, stuck in a horizontal temporality, organised by the clock, that flattens our work, our words? In reading feminist work by Märta Tikkanen, Hélène Cixous, and others, a rupture strikes, establishing another temporality: vertical time. Is it possible, I ask, to learn from these authors and engage in academic writing in verticality? The answer is: Yes! Through an in-depth reading of special pieces, I see clearly that when we use our scholarly voice to write from within our vulnerabilities, it becomes possible to climb all the way up or dig ourselves deep down. In other words, we can ‘go deep’ in the sense of touching that which is most important, as well as finding ways to ‘fly high,’ through writing. This shows that writing and temporality are always already interweaved with each other because writing produces temporalities just as temporality at play produces writing. In this writing-temporality meshwork, there seems to be no set genre for vertical writing. Rather, it consists of a multitude of practices, written in the instant, from within the urgency of articulating that which matters.
Intracortical motor conduction is associated with hand dexterity in progressive multiple sclerosis
Authors: Pisa Marco , Chieffo Raffaella , Congiu Martina , Dalla Costa Gloria , Esposito Federica , Romeo Marzia , Comola Mauro , Comi Giancarlo , Leocani Letizia
Published: September 2020

Background:

Hand dexterity dysfunction is a key feature of disability in people with progressive multiple sclerosis (PMS). It underlies corticospinal tract (CST) and cerebellar integrity, as well as disruption of cortical networks, which are hardly assessed by standard techniques. Transcranial magnetic stimulation is a promising tool for evaluating the integrity of intracortical motor pathways.

Objective:

To investigate neurophysiological correlates of motor hand impairment in PMS.

Methods:

Antero-posterior (AP) stimulation of the primary motor cortex activates the CST indirectly through polysynaptic pathways, while a direct CST activation occurs with latero-medial (LM) directed current. Thirty PMS and 15 healthy controls underwent dominant hand motor evoked potentials (MEP) using AP and LM-directed stimulation, and a clinical assessment of dexterity (nine-hole peg test) and strength (MRC scale, grip and pinch).

Results:

PMS with AP-LM latency difference 2.5 standard deviation above the mean of controls (33%) showed worse dexterity but no difference in upper limb strength. Accordingly, AP-LM latency shortening predicted dexterity (R2 = 0.538, p < 0.001), but not strength impairment. On the contrary, absolute MEP latencies only correlated with strength (grip: R2 = 0.381, p = 0.014; MRC: R2 = 0.184, p = 0.041).

Conclusion:

AP-LM latency shortening may be used to assess the integrity polysynaptic intracortical networks implicated in dexterity impairment.
Social responses to and motivation involving knitting vlog viewing
Authors: Gregg Peter B
Published: September 2020

This project explores social psychological factors and motivation involving vlogs, filling gaps in the understanding of viewing needs and outcomes of this new cultural practice. An exploratory online survey asked over 400 knitting vlog viewers about expected outcomes of viewing, loneliness, identification, perceived homophily, parasocial relationship strength, motivation to knit, and motivation to view knitting vlogs, addressing hypotheses involving common expected outcomes and viewing motivation, how well loneliness predicts parasocial relationship strength, and how these feelings predict motivations to view vlogs and to knit. The results showed that feelings of activity and social connection most strongly predicted motivation to view and to knit. Loneliness did not play a role in parasocial relationship strength. These findings suggest that the social qualities of knitting vlogs may play an important role in motivating viewers to watch and to knit.
Finding love: The materialities of love-locks and geocaches
Authors: Houlbrook Ceri , Parker Adam
Published: September 2020

This article is the product of a collaboration between a folklorist researching the global phenomenon of love-locks (padlocks attached to public structures in declaration of romantic commitment) and an archaeologist who also happens to be a player of ‘Geocaching’ (a real-world, outdoor treasure hunting game using GPS-enabled devices). A chance discussion between the two revealed significant overlaps between love-locking and geocaching, despite the two practices being divergent in function and intention. Some overlaps are tangible, with love-locks forming an integral component of a number of geocaches worldwide. Other overlaps are theoretical, with both practices resulting in contemporary assemblages, or ‘serial collaborative creations’, fundamentally driven by the relationships between objects, places and human participants. The question driving this article is: what can we learn about these two seemingly different customs by considering where they overlap?
Consuming UK Transnational Higher Education in China: A Bourdieusian Approach to Chinese Students’ Perceptions and Experiences
Authors: Yu Jingran
Published: September 2020

Recently, the increased scale and complexity of ‘student-as-consumer’ discourse has become well-established within the intensifying neoliberal marketisation across higher education in the Global North. However, few insights have been generated within a transnational education context. This article is based on a case study of a UK transnational higher education institution in China, where market-based rationalities converge with a centralised statist agenda. It demonstrates that Chinese students’ perceptions and experiences of patriotism education and international education, as well as their own strategy of obtaining a transnational education as an investment, were shaped by the unequal power relations between China and the UK in the global classification of knowledge. They tend to highly value UK higher education in both material and immaterial forms, associating it with ‘humanitarianism’ and disinterestedness. This article concludes that the profit-making agenda of the UK is veiled by its symbolic power, while the nation-building effort of China has driven the students further away. As a result, Chinese students voluntarily participate in the reproduction of symbolic power of UK higher education in the hierarchically structured global field.
Joint modelling of longitudinal and survival data in the presence of competing risks with applications to prostate cancer data
Authors: Sheikh Md Tuhin , Ibrahim Joseph G , Gelfond Jonathan A , Sun Wei , Chen Ming-Hui
Published: September 2020

This research is motivated from the data from a large Selenium and Vitamin E Cancer Prevention Trial (SELECT). The prostate specific antigens (PSAs) were collected longitudinally, and the survival endpoint was the time to low-grade cancer or the time to high-grade cancer (competing risks). In this article, the goal is to model the longitudinal PSA data and the time-to-prostate cancer (PC) due to low- or high-grade. We consider the low-grade and high-grade as two competing causes of developing PC. A joint model for simultaneously analysing longitudinal and time-to-event data in the presence of multiple causes of failure (or competing risk) is proposed within the Bayesian framework. The proposed model allows for handling the missing causes of failure in the SELECT data and implementing an efficient Markov chain Monte Carlo sampling algorithm to sample from the posterior distribution via a novel reparameterization technique. Bayesian criteria, [Formula: see text]DIC[Formula: see text], and [Formula: see text]WAIC[Formula: see text], are introduced to quantify the gain in fit in the survival sub-model due to the inclusion of longitudinal data. A simulation study is conducted to examine the empirical performance of the posterior estimates as well as [Formula: see text]DIC[Formula: see text] and [Formula: see text]WAIC[Formula: see text] and a detailed analysis of the SELECT data is also carried out to further demonstrate the proposed methodology.
Partnerships in nursing homes: How do family caregivers of residents with dementia perceive collaboration with staff?
Authors: Hoek Linda JM , van Haastregt Jolanda CM , de Vries Erica , Backhaus Ramona , Hamers Jan PH , Verbeek Hilde
Published: September 2020

Background

Partnerships between family and nursing staff in nursing homes are essential to address residents’ needs and wishes. Collaboration is needed to create partnerships; nonetheless, challenges exist.

Aim

This study aimed to gain insights into the experiences of families collaborating with staff.

Method

Semi-structured interviews were held with 30 family caregivers of nursing home residents with dementia.

Findings

Data reflected three themes, which shaped collaboration with staff from families’ perspective, ‘communication’, ‘trust and dependency’ and ‘involvement’.

Discussion

Good communication appeared to be a requisite condition for having trust in staff and quality of involvement in residents’ life. Good communication was described as having informal contact with staff, which enabled family and staff to build a personal connection. Consequently, this seemed to increase trust and satisfaction regarding involvement.

Conclusion

Findings suggest that increasing informal contact and building a personal connection should be a priority for staff in order to improve collaboration and to create partnerships with families.
Numerical investigation of porous materials for trailing edge noise reduction
Authors: Rossian Lennart , Ewert Roland , Delfs Jan W
Published: September 2020

In the framework of the German Collaborative Research Center CRC 880: Fundamentals of High Lift for Future Civil Aircraft porous materials as a means towards the reduction of airfoil trailing edge noise are investigated. At DLR, both experimental and numerical approaches are pursued to understand the physics behind the noise reduction. The present paper focuses on the numerical investigations, for which the experimental data serves as an evaluation basis. From the analysis of homogeneous materials, first steps are made towards the design of aeroacoustically tailored materials. It is assumed that materials with locally varying permeability may be suitable to achieve maximum noise reduction, as they provide a smooth transition from the solid airfoil to the free flow in the wake. The simulation results support this understanding, however it is revealed that high local gradients in the material properties themselves may act as acoustic sources.
Solanine Attenuates Hepatocarcinoma Migration and Invasion Induced by Acetylcholine
Authors: Lin Liang-Tzung , Choong Chen-Yen , Tai Chen-Jei
Published: September 2020

Aim:

Evidence has provided an explanation of the correlation between the nervous system and the tumor microenvironment. Neurotransmitters may be involved in different aspects of cancer progression. The glycoalkaloid solanine has been reported to suppress neural signaling pathways and exists in numerous plants, including Solanum nigrum, which have been demonstrated to inhibit cancer cell proliferation.

Methods:

We evaluated the potentials of solanine on inhibiting acetylcholine-induced cell proliferation and migration in hepatocellular carcinoma cells.

Results:

The results indicated that solanine markedly attenuated cell proliferation and migration via inhibiting epithelial-mesenchymal transition and matrix metalloproteinases in acetylcholine-treated Hep G2 cells. In addition, exosomes derived from acetylcholine-treated Hep G2 cells were isolated, and solanine showed inhibiting effects of extrahepatic metastasis on blocking cell proliferation in exosome-treated A549 lung carcinoma cells through regulating microRNA-21 expression.

Conclusion:

Solanine has strong potential for application in integrative cancer therapy.
C-C Motif Chemokine 8 promotes angiogenesis in vascular endothelial cells
Authors: Xue Song , Tang Hanfei , Zhao Gefei , Shen Yang , Yang Ethan Yibo , Fu Weiguo , Shi Zhenyu , Tang Xiao , Guo Daqiao
Published: September 2020

Objectives

Angiogenesis is an important progress associated with several pathological situations. Several chemokines have been reported to act as regulators of angiogenesis. The current study aimed to find whether C-C Motif Chemokine 8 is involved in angiogenesis regulation.

Methods

To verify whether C-C Motif Chemokine 8 is related to angiogenesis in plaques, carotid plaques were collected from patients with severe carotid stenosis and analysed using CD31 immunohistochemistry and real-time PCR. To further clarify the relation between C-C Motif Chemokine 8 and angiogenesis, human umbilical vein endothelium cells and human dermal microvascular endothelial cells were treated with C-C Motif Chemokine 8 in the presence or absence of C-C motif chemokine receptor 2-Ab and extracellular regulated MAP kinase 1/2 inhibition (FR180204). Proliferation and migration of human umbilical vein endothelium cells and human dermal microvascular endothelial cells were examined with Cell Counting Kit-8 and Transwell chamber assay, respectively. In vitro angiogenesis stimulated by C-C Motif Chemokine 8 was examined using tube formation assay. Ex vivo and in vivo angiogenesis were assessed by mice aortic ring assay and Matrigel plug assay, respectively. C-C motif chemokine receptors of human umbilical vein endothelium cells were examined with real-time PCR, and C-C motif chemokine receptor 1, C-C motif chemokine receptor 2, extracellular regulated MAP kinase 1/2 and phosphorylation-extracellular regulated MAP kinase 1/2 were examined with western blotting assay.

Results

C-C Motif Chemokine 8 was increased in carotid plaques with severe angiogenesis in both RNA and protein level. C-C Motif Chemokine 8 (5 ng/ml) weakly increased human umbilical vein endothelium cell proliferation, but not on human dermal microvascular endothelial cells. Migration and tube formation could be induced by C-C Motif Chemokine 8 in both human umbilical vein endothelium cells and human dermal microvascular endothelial cells. In mice aortic ring assay and Matrigel plug assay, C-C Motif Chemokine 8 could promote angiogenesis compared to vehicle groups. Phosphorylation of extracellular regulated MAP kinase 1/2 was increased with C-C Motif Chemokine 8 stimulation. The migration and tube formation promoted by C-C Motif Chemokine 8 could be largely blocked by C-C motif chemokine receptor 2-Ab or extracellular regulated MAP kinase 1/2 inhibition (FR180204).

Conclusions

C-C Motif Chemokine 8 could promote both in vitro and in vivo angiogenesis. C-C motif chemokine receptor 2 played an important role in the activation of C-C Motif Chemokine 8 and extracellular regulated MAP kinase 1/2 signalling pathway was involved in this mechanism.
“Clearly they are in the circle of care, but . . .”: A qualitative study exploring perceptions of personal health information sharing with community pharmacists in an integrated care model
Authors: Rolf von den Baumen Teagan , Lake Jennifer , Everall Amanda C. , Dainty Katie , Rosenberg-Yunger Zahava , Guilcher Sara J. T.
Published: September 2020

Background:

Ontario’s Health Links approach to care is an integrated care model designed to optimize care for patients with complex needs. Currently, community pharmacists have no formalized role. This study aimed to explore stakeholders’ perceptions about privacy and its impact on community pharmacists’ involvement with integrated care models.

Methods:

A qualitative study using semistructured telephone-based interviews was conducted. Participants worked in Ontario as pharmacists, providers in Health Links or team-based models or decision-makers in Health Links or health regions. Thematic analysis followed the Qualitative Analysis Guide of Leuven.

Results:

Twenty-two participants were interviewed, and all but one commented on privacy or information sharing in integrating community pharmacists with integrated care models. The 4 themes identified were as follows: 1) what does the circle of care look like? 2) value of sharing information, 3) uncertainty of what information to share and 4) perceptions on how to share information.

Interpretation:

The concerns surrounding privacy of personal health information and who is included in the circle of care represented an important barrier for integration. Enablers to mitigate privacy concerns included relationship building between community pharmacists, patients and other health care professionals and mutual access to information-sharing platforms such as electronic health records.

Conclusion:

Providers’ and decision-makers’ perceptions about community pharmacists and privacy affect information sharing and are incongruent with Ontario’s Personal Health Information Protection Act. Education is needed for health care professionals on legislation, especially as health systems move towards integrated care models to improve care. Can Pharm J (Ott) 2020;153:xx-xx.
The relationship between body mass index and the risk of development of Dupuytren’s disease: a Mendelian randomization study
Authors: Majeed Mustafa , Wiberg Akira , Ng Michael , Holmes Michael V. , Furniss Dominic
Published: September 2020

We performed Mendelian randomization analyses of body mass index and waist–hip ratio adjusted for body mass index in Dupuytren’s disease using summary statistics from genome-wide association study meta-analyses. We found that adiposity is causally protective against Dupuytren’s disease, with the inverse-variance weighted Mendelian randomization analysis estimating that a 1 standard deviation increase in body mass index (equivalent to 4.8 kg/m2) leads to 28% (95% confidence interval: 18–37%) lower relative odds of developing Dupuytren’s disease, and a 1 standard deviation increase in waist–hip ratio adjusted for body mass index (equivalent to a waist–hip ratio of 0.09) leads to 26% (95% confidence interval: 6–42%) lower relative odds of developing Dupuytren’s disease. We conclude from this study that regardless of the well-established negative health effects of obesity, the raised body mass index is associated with a lower risk of Dupuytren’s disease and may be causally protective for the development of the disease.
‘As if by osmosis’: How Ofsted’s new deficit model emerged, fully formed, as cultural capital
Authors: Nightingale Paul
Published: September 2020

This paper considers recent developments in English education policy as, confirming promises made in the 2016 White Paper, Educational Excellence Everywhere, schools are now to concentrate on the realisation of a knowledge-based curriculum, one that allows all students to ‘acquire’ cultural capital. First, the remodelling of Bourdieu’s concept, designed to explain class privilege, means that the cultural capital is now a mechanism for disciplining schools and teachers who fail to deliver the required curriculum. Second, in going beyond the social inclusion advocated by previous governments, this version of cultural capital has simply recycled the 1950s notion of cultural deprivation, turning it into a ‘knowledge deficit’ to be explained with reference to the work of ED Hirsch. It remains to be seen if ‘Hirsch-knowledge’ offers anything more than passive consumption of approved content, and the paper ends with a discussion of the implications for students of the new curriculum.
Impact of COVID-19 outbreak in an Italian cohort of patients with systemic sclerosis
Authors: Del Papa Nicoletta , Sambataro Gianluca , Minniti Antonina , Maglione Wanda , Pignataro Francesca , Caminati Antonella , Harari Sergio , Sambataro Domenico , Vitali Claudio , Caporali Roberto Felice
Published: September 2020

Background:

Mortality rate in patients infected by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can be related to the presence of comorbidities like diabetes, cardiovascular and pulmonary diseases. On the contrary, few data exist on the impact of CoronaVirus Disease 2019 (COVID-19) on patients with rheumatic disorders, namely in those having pulmonary involvement and treated with immunosuppressive agents. The present survey is aimed at knowing the impact of COVID-19 in a cohort of patients with systemic sclerosis (SSc).

Methods:

Telephone interviews were carried out during the COVID-19 outbreak in patients with SSc followed in a Rheumatic Disease Unit in Italy. Patients were asked for confirmed SARS-CoV-2 infection, symptoms suggestive of COVID-19, and modification of their therapy.

Results:

A total number of 526 patients with SSc were contacted and interviewed. Of them, 270 and 256 had limited cutaneous and diffuse cutaneous SSc, respectively. Interstitial lung disease (ILD) was present in 45% of patients and most of them (68.2%) were treated with immunosuppressive therapy. Only two patients were hospitalized for COVID-19-related pneumonia, and one of them died despite invasive ventilator support. An additional 11 patients reported flu-like symptoms compatible with a mild form of COVID-19. Nobody modified the therapy during the COVID-19 outbreak.

Conclusion:

Despite the large prevalence of ILD and immunosuppressive therapies, which can be considered risk factors for the occurrence and severity of incidental viral infections, the impact of COVID-19, in terms of mortality rate and morbidity, does not appear particularly severe in this large cohort of patients with SSc. Possible mechanisms influencing this figure are discussed.
The Beautiful Complexity of Human Prosociality: On the Interplay of Honesty-Humility, Intuition, and a Reward System
Authors: Nockur Laila , Pfattheicher Stefan
Published: September 2020

Human prosociality is a fascinating and complex phenomenon. The present research takes this complexity into account by examining the interplay of three prominent factors that past research has shown to promote prosocial behavior. In two studies (total N = 1,799), we tested the impact of (a) a basic prosocial personality trait (the Honesty-Humility dimension from the HEXACO personality model), (b) intuitive decision making, and (c) the possibility of being rewarded (i.e., a reward system) in the emergence of prosocial behavior (i.e., dictator game giving). Replicating previous research, we found that (1) a reward system increased prosocial behavior and (2) Honesty-Humility was positively related to prosocial behavior. In addition, given that there was no reward system, we show that intuition (vs. a control condition) reduced prosocial behavior in individuals low in Honesty-Humility, whereas no effect was found for individuals high in Honesty-Humility. Implications for the understanding of prosocial behavior are discussed.
Clinical evidences on the antiviral properties of macrolide antibiotics in the COVID-19 era and beyond
Authors: Poddighe Dimitri , Aljofan Mohamad
Published: September 2020

Macrolides are a large group of antibiotics characterised by the presence of a macro-lactone ring of variable size. The prototype of macrolide antibiotics, erythromycin was first produced by Streptomyces and associated species more than half a century ago; other related drugs were developed. These drugs have been shown to have several pharmacological properties: in addition to their antibiotic activity, they possess some anti-inflammatory properties and have been also considered against non-bacterial infections. In this review, we analysed the available clinical evidences regarding the potential anti-viral activity of macrolides, by focusing on erythromycin, clarithromycin and azithromycin. Overall, there is no significant evidences so far that macrolides might have a direct benefit on most of viral infections considered in this review (RSV, Influenza, coronaviruses, Ebola and Zika viruses). However, their clinical benefit cannot be ruled out without further and focused clinical studies. Macrolides may improve the clinical course of viral respiratory infections somehow, at least through indirect mechanisms relying on some and variable anti-inflammatory and/or immunomodulatory effects, in addition to their well-known antibacterial activity.
Broaching the brook: Daylighting, community and the ‘stickiness’ of water
Authors: Usher Mark , Huck Jonathan , Clay Gareth , Shuttleworth Emma , Astbury Janice
Published: September 2020

Over the last century, under the modern hydraulic model, waterways across the world have been heavily canalized and culverted, driven into underground pipes, drains and sewers. This hydraulic approach has hardwired an isolated water network into the urban fabric, fragmenting erstwhile patterns and dynamics of life, both human and nonhuman. Ecologically, it has been hugely damaging, reducing water quality and biotic diversity, but also socially, disconnecting citizens from the waterways that service and characterize the city. Consequently, since the 1990s, waterway restoration has become widespread as a design solution to degraded rivers and streams, reinstating compromised hydrological, geomorphological and ecological processes. Deculverting or ‘daylighting’, the focus of this paper, is a radical form of restoration, opening up subterranean, culverted waterways often forgotten by communities above ground. Yet, as this paper emphasizes, waterway restoration has tended to privilege ecological over social objectives, while public engagement in project conceptualization has been limited, conducted ‘downstream’ subsequent to planning and design stages. Restoration schemes have therefore tended to reflect the concerns of professionals rather than communities, overlooking their potential for social renewal and change. Drawing on workshop data collected through participatory mapping exercises, this paper explores the case for daylighting a culverted brook in Urmston, Greater Manchester, focusing in particular on the preferences, concerns and knowledge of local residents. The paper compares professional and community perspectives on the preferred scheme design and potential benefits of daylighting, drawing out differences and tensions between them, temporarily ‘unblackboxing’ the brook. It is ventured that daylighting can unleash the social ‘stickiness’ of water, its proclivity to draw and bind together, to revitalize the park, enhancing connection to wildness, attachment to place and sense of community. This is particularly crucial in the face of decreased local authority funding and related crises in park management.
From Commitment to Passion: Appraising the Energy of Millennials
Authors: Kumbla Praveen Kamath
Published: September 2020

As millennials increasingly become a part of the workforce, it is necessary to understand what this implies for the future of work. Millennials signify a shift in traditional employment models premised on commitment. Instead, they bring in an ethical passion to connect business with social issues and transform the world. In the process, millennials will have to negotiate with a range of powerful stakeholders to leave a distinct mark on business and society. It is useful for millennials to spend time in understanding their audience and articulating their thoughts in ways that can persuade their audience.
Expanded Byrne model for evaluating seismic compression
Authors: Jiang Yusheng , Green Russell A , Taylor Oliver-Denzil
Published: September 2020

Seismic compression is the accrual of contractive volumetric strain in unsaturated or partially saturated sandy soils during earthquake shaking and has caused significant distress to overlying and nearby structures. The phenomenon can be well characterized by load-dependent, interaction macro-level fatigue theories. Toward this end, the Byrne cyclic shear-volumetric strain coupling model is expanded and calibrated for evaluating seismic compression for several soil types. In addition, the model was transformed to allow it to be implemented in a “simplified” manner, in addition to the original “non-simplified” formulation. Both implementation approaches are used to analyze a site in Japan impacted by the 2007, Mw6.6 Niigata-ken Chuetsu-oki earthquake. The results from the analyses are in general accord with the post-earthquake field observations and highlight the sensitivity of predicted magnitude of the seismic compression to the input variables used and modeling assumptions (e.g. relative density of the soil, magnitude of the volumetric threshold strain, orientation of the ground motions, settlement of soils below the ground water table, and accounting for multidirectional shaking). Although additional studies are needed to further validate the findings presented herein, estimation of relative density and threshold shear strain of the soil and ground motion orientation individually have moderate-to-significant influence on the computed magnitude of seismic compression, but they have a significant influence when taken in combination. Also, the seismic compression models can seemingly be used to predict the settlement in fully saturated sand when the excess pore water pressures are limited. Finally, accounting for multidirectional shaking has a significant influence on the computed magnitude of seismic compression.
Effect of hydroxyurea exposure before puberty on sperm parameters in males with sickle cell disease
Authors: Joseph L. , Jean C. , Manceau S. , Chalas C. , Arnaud C. , Kamdem A. , Pondarré C. , Habibi A. , Bernaudin F. , Allali S. , de Montalembert M. , Boutonnat-Faucher B. , Arlet J.-B. , Koehl B. , Cavazzana M. , Ribeil J.-A. , Lionnet F. , Berthaut I. , Brousse V.
Published: September 2020

Sperm parameters are known to be impaired in men with sickle cell disease (SCD). Although treatment with hydroxyurea (HU) has an impact on sperm quality, sperm preservation is impossible before puberty. This study’s primary objective was to analyze and compare sperm parameters in male patients with SCD exposed (or not) to HU before puberty. Twenty-six sperm samples from 15 patients (median age, 17 years; range, 16-23) treated with HU during childhood were compared with 46 samples from 23 HU-naïve patients (20 years; 16-24). The median age at HU initiation was 6 years (1-14 years), the median duration of HU treatment was 4 years (0.5-10), and the mean dose of HU was 22.4 ± 3.7 mg/kg per day. Although we observed substantial quantitative and qualitative semen abnormalities in all patients, there were no significant differences in semen volume, sperm concentration, total sperm count, or spermatozoa motility, morphology, and vitality between the HU-exposed and HU-naïve groups. At the time of the semen analysis, 100% of the patients in the HU-exposed group and 52% of the patients in the HU-naïve group received transfusion therapy. The specific effect of HU on spermatogenesis in very young infants and the putative value of transfusion for reversing the toxicity of HU warrant further investigation.
Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: an observational cohort study
Authors: Gupta Rishi K. , Marks Michael , Samuels Thomas H.A. , Luintel Akish , Rampling Tommy , Chowdhury Humayra , Quartagno Matteo , Nair Arjun , Lipman Marc , Abubakar Ibrahim , van Smeden Maarten , Wong Wai Keong , Williams Bryan , Noursadeghi Mahdad
Published: September 2020

The number of proposed prognostic models for coronavirus disease 2019 (COVID-19) is growing rapidly, but it is unknown whether any are suitable for widespread clinical implementation.

We independently externally validated the performance of candidate prognostic models, identified through a living systematic review, among consecutive adults admitted to hospital with a final diagnosis of COVID-19. We reconstructed candidate models as per original descriptions and evaluated performance for their original intended outcomes using predictors measured at the time of admission. We assessed discrimination, calibration and net benefit, compared to the default strategies of treating all and no patients, and against the most discriminating predictors in univariable analyses.

We tested 22 candidate prognostic models among 411 participants with COVID-19, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. Highest areas under receiver operating characteristic (AUROC) curves were achieved by the NEWS2 score for prediction of deterioration over 24 h (0.78, 95% CI 0.73–0.83), and a novel model for prediction of deterioration <14 days from admission (0.78, 95% CI 0.74–0.82). The most discriminating univariable predictors were admission oxygen saturation on room air for in-hospital deterioration (AUROC 0.76, 95% CI 0.71–0.81), and age for in-hospital mortality (AUROC 0.76, 95% CI 0.71–0.81). No prognostic model demonstrated consistently higher net benefit than these univariable predictors, across a range of threshold probabilities.

Admission oxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the prognostic models evaluated here offered incremental value for patient stratification to these univariable predictors.
Primary ciliary dyskinesia: a major player in a bigger game
Authors: Bhatt Reena , Hogg Claire
Published: September 2020

Primary ciliary dyskinesia (PCD) is an inherited disorder of clinical and genetic heterogeneity resulting from mutations in genes involved in the transport, assembly and function of motile cilia. The resulting impairment in mucociliary clearance means patients suffer from chronic progressive lung disease, bronchiectasis, rhinosinusitis and middle ear disease. Subfertility is common to both male and female patients. Situs abnormalities occur in around half of patients, with a subgroup suffering more complex situs arrangements where congenital heart defects or other organ abnormalities frequently coexist. Variations from the classical PCD phenotype are increasingly recognised where overlapping features across a range of motile and nonmotile ciliopathies are redefining our approach to both diagnosis and management of these complex conditions. PCD offers an ideal opportunity for direct visualisation of ciliary function and structure, following nasal brush biopsy, allowing opportunities for researchers to directly interrogate the downstream impact of loss of function mutations. In turn, this has led to rapid advances in the development of new diagnostic tests. These advances mean that PCD is an excellent disease model for understanding the genetic and mechanistic causes of the clinical phenotype for all respiratory ciliopathies. Furthermore, the overlapping role of motile ciliary defects in a wider set of complex and syndromic disorders related to loss of function mutations in primary, nonmotile cilia has been recognised. As we better understand the role of ciliary defects in a broad spectrum of diseases, we should aim to map out a framework through which we can identify, diagnose and treat all respiratory ciliopathies.

Key points

Primary ciliary dyskinesia is just one of a group of conditions where a heterogeneous array of genetic mutations affect the assembly or structure of motile cilia.

Overlapping phenotypes between motile and nonmotile ciliopathies are redefining the diagnostic and therapeutic approach to encompass all ciliopathy patients with a respiratory phenotype.

An extended diagnostic algorithm may be required to capture the majority of cases with a respiratory ciliopathy, including patients with syndromic ciliopathies.

The terminology around disorders of motile cilia is becoming more descriptive to better reflect the heterogeneity and underlying disease mechanisms across the spectrum of respiratory ciliopathies.

Educational aims

To summarise the existing knowledge base around the disease mechanisms for respiratory ciliopathies, including primary ciliary dyskinesia (PCD).

To explore and understand the reasons for changing terminology around respiratory ciliopathies.

To emphasise key messages around the diagnosis and treatment of all ciliopathies.

Diagnosing PCD is complex and time consuming, and there is no single stand-alone test that can confirm or exclude a diagnosis in all cases.
European Headache Federation recommendations for placebo and nocebo terminology
Authors: Mitsikostas Dimos D. , Blease Charlotte , Carlino Elisa , Colloca Luana , Geers Andrew L. , Howick Jeremy , Evers Andrea W. M. , Flaten Magne A. , Kelley John M. , Kirsch Irving , Klinger Regine , MaassenVanDenBrink Antoinette , Moerman Daniel E. , Sfikakis Petros P. , Vase Lene , Wager Tor D. , Benedetti Fabrizio ,   on behalf of the European Headache Federation
Published: September 2020

Background and aim

Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials.

Methods

The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented.

Results/recommendations

Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term “placebo response” should be used, and for any unfavorable outcome recorded after placebo administration, the term “nocebo response” should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms “placebo” and “nocebo” (“placebos” and “nocebos” in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement).

Conclusion

The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).
A novel approach to minimally invasive hysterectomy without the use of a uterine manipulator: Kamran’s TLH technique
Authors: Gendia Ahmed M. , Donlon Noel E. , Kamran Waseem M.
Published: September 2020

Background

There are a number of techniques documented in the literature to perform laparoscopic hysterectomy, and here, we propose a safe and novel technique that obviates the need for a pelvic assistant, removes the need for a uterine manipulator and can potentially reduce operative duration.

Results

Total laparoscopic hysterectomy can be approached without the use of uterine manipulator or vaginal tubes using the steps demonstrated.

Conclusions

This novel technique is safe, efficient and conducive to standardising minimally invasive hysterectomy practices obviating the need for a uterine manipulator and pelvic assistant.