bluuebunny/crossref_metadata_2025 huggingface dataset:
kTWAS: Integrating kernel-machine with transcriptome-wide association studies improves statistical power and reveals novel genes
Authors: Cao Chen , Kwok Devin , Edie Shannon , Li Qing , Ding Bowei , Kossinna Pathum , Campbell Simone , Wu Jingjing , Greenberg Matthew , Long Quan
Published: June 2020

The power of genotype-phenotype association mapping studies increases greatly when contributions from multiple variants in a focal region are meaningfully aggregated. Currently, there are two popular categories of variant aggregation methods. Transcriptome-wide association studies (TWAS) represent a category of emerging methods that select variants based on their effect on gene expressions, providing pretrained linear combinations of variants for downstream association mapping. In contrast, kernel methods such as SKAT model genotypic and phenotypic variance using various kernel functions that capture genetic similarity between subjects, allowing non-linear effects to be included. From the perspective of machine learning, these two methods cover two complementary aspects of feature engineering: feature selection/pruning, and feature modeling. Thus far, no thorough comparison has been made between these categories, and no methods exist which incorporate the advantages of TWAS and kernel-based methods. In this work we developed a novel method called kTWAS that applies TWAS-like feature selection to a SKAT-like kernel association test, combining the strengths of both approaches. Through extensive simulations, we demonstrate that kTWAS has higher power than TWAS and multiple SKAT-based protocols, and we identify novel disease-associated genes in WTCCC genotyping array data and MSSNG (Autism) sequence data. The source code for kTWAS and our simulations are available in our GitHub repository (https://github.com/theLongLab/kTWAS).
Wide field-of-view volumetric imaging by a mesoscopic scanning oblique plane microscopy with switchable objective lens
Authors: Shao Wenjun , Kilic Kivilcim , Yin Wenqing , Wirak Gregory , qin Xiaodan , Feng Hui , Boas David , Gabel Christopher V. , Yi Ji
Published: June 2020

Conventional light sheet fluorescence microscopy (LSFM), or selective plane illumination microscopy (SPIM), enables high resolution 3D imaging over a large volume by using two orthogonally aligned objective lenses to decouple excitation and emission. The recent development of oblique plane microscopy (OPM) simplifies LSFM design with only one single objective lens, by using off-axis excitation and remote focusing. However, most reports on OPM has a limited microscopic field of view (FOV), typically within 1×1 mm2. Our goal is to overcome the limitation with a new variant of OPM to achieve mesoscopic FOV. We implemented an optical design of mesoscopic scanning OPM to allow using low numerical aperture (NA) objective lens. The angle of the intermediate image before the remote focusing system was increased by a demagnification under Scheimpflug condition such that the light collecting efficiency in the remote focusing system was significantly improved. We characterized the 3D resolutions and FOV by imaging fluorescence microspheres, and demonstrated the volumetric imaging on intact whole zebrafish larvae, mouse cortex, and multipleCaenorhabditis elegans (C.elegans). We demonstrate a mesoscopic FOV up to ~6× 5×0.6 mm3volumetric imaging, the largest reported FOV by OPM so far. The angle of the intermediate image plane is independent of the magnification. As a result, the system is highly versatile, allowing simple switching between different objective lenses with low (10x, NA 0.3) and median NA (20x, NA 0.5). Detailed microvasculature in zebrafish larvae, mouse cortex, and neurons inC. elegansare clearly visualized in 3D. The proposed mesoscopic scanning OPM allows using low NA objective such that centimeter-level FOV volumetric imaging can be achieved. With the extended FOV, simple sample mounting protocol, and the versatility of changeable FOVs/resolutions, our system will be ready for the varieties of applications requiringin vivovolumetric imaging over large length scales.
The Prevalence of ocular manifestations and ocular samples polymerase chain reaction positivity in patients with COVID 19 - a systematic review and meta-analysis
Authors: Sadhu Soumen , Dandapani Sushmitha Arcot , Mazumdar Deepmala , Srinivasan Sangeetha , Biswas Jyotirmay
Published: June 2020

Objective

To estimate the prevalence of ocular manifestations and ocular samples polymerase chain reaction (PCR) positivity among COVID-19 patients.

Methods

A systematic literature review was performed using search engines (PubMed, Google Scholar, Medrixv and BioRixv) with keywords “SARS-CoV-2”, “novel coronavirus”, “COVID-19”, “ocular manifestations”, “conjunctival congestion”, “Ocular detection”, “Polymerase chain reaction”, and “conjunctivitis”. The measure of heterogeneity was evaluated with the I2statistic. The pooled proportion of patients presenting with symptoms and ocular samples PCR positivity was estimated.

Results

A total of 20 studies (14 studies and 6 case-reports) were included in the systematic review and 14 studies were included in the meta-analysis. The pooled prevalence of conjunctivitis was 5.17% (95% CI: 2.90-8.04). Conjunctivitis was reported as an initial symptom of the disease in 0.858 % (95% CI: 0.31-1.67). Common associated features include itching, chemosis, epiphora. Seven patients (29 %) with conjunctivitis showed positive results in ocular samples, whereas 13 patients (54%) showed positive only in theirnasopharyngeal samples (NPs) orsputum samples and 4 patients (16 %) were negative for both NPs and Sputum as well as ocular samples. The pooled prevalence of ocular PCR positivity was 2.90 % (95% CI: 1.77 – 4.46) vs. NPs 89.8% (95% CI: 78.80-79.0).

Conclusion

The prevalence of conjunctivitis and ocular samples PCR positivity among COVID-19 patients was low indicating that the eye is a less affected organ. However, conjunctivitis may present as the first symptom of the disease making the patient seek medical care at the earliest.

Synopsis

Viral conjunctivitis was the only symptom reported. The prevalence of conjunctivitis and ocular samples polymerase chain reaction positivity among COVID-19 patients was low indicating the eye is a less effected organ.
Derived crystal structure of martensitic materials by solid–solid phase transformation
Authors: Karami Mostafa , Tamura Nobumichi , Yang Yong , Chen Xian
Published: June 2020

A mathematical description of crystal structure is proposed consisting of two parts: the underlying translational periodicity and the distinct atomic positions up to the symmetry operations in the unit cell, consistent with theInternational Tables for Crystallography. By the Cauchy–Born hypothesis, such a description can be integrated with the theory of continuum mechanics to calculate a derived crystal structure produced by solid–solid phase transformation. In addition, the expressions for the orientation relationship between the parent lattice and the derived lattice are generalized. The derived structure rationalizes the lattice parameters and the general equivalent atomic positions that assist the indexing process of X-ray diffraction analysis for low-symmetry martensitic materials undergoing phase transformation. The analysis is demonstrated in a CuAlMn shape memory alloy. From its austenite phase (L21face-centered cubic structure), it is identified that the derived martensitic structure has orthorhombic symmetryPmmnwith the derived lattice parametersad= 4.36491,bd= 5.40865 andcd= 4.2402 Å, by which the complicated X-ray Laue diffraction pattern can be well indexed, and the orientation relationship can be verified.
Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel
Authors: Fourati Zaineb , Sauguet Ludovic , Delarue Marc
Published: June 2020

GLIC is a bacterial homologue of the pentameric ligand-gated ion channels (pLGICs) that mediate the fast chemical neurotransmission of nerve signalling in eukaryotes. Because the activation and allosteric modulation features are conserved among prokaryotic and eukaryotic pLGICs, GLIC is commonly used as a model to study the allosteric transition and structural pharmacology of pLGICs. It has previously been shown that GLIC is inhibited by some carboxylic acid derivatives. Here, experimental evidence for carboxylate binding to GLIC is provided by solving its X-ray structures with a series of monocarboxylate and dicarboxylate derivatives, and two carboxylate-binding sites are described: (i) the `intersubunit' site that partially overlaps the canonical pLGIC orthosteric site and (ii) the `intrasubunit' vestibular site, which is only occupied by a subset of the described derivatives. While the intersubunit site is widely conserved in all pLGICs, the intrasubunit site is only conserved in cationic eukaryotic pLGICs. This study sheds light on the importance of these two extracellular modulation sites as potential drug targets in pLGICs.
Continuous improvement of the industrialised housebuilding order fulfilment process
Authors: Grenzfurtner Wolfgang , Gronalt Manfred
Published: June 2020

Purpose

A deeper understanding of what needs to be considered to improve the targeted incorporation of employees’ knowledge into continuous improvement (CI) programmes in industrialised housebuilding (IHB) is required. This paper aims to address the current lack of involvement and connect it to structural and corporate culture factors. To avoid misjudgements in improvement activities as well as to use the full potential of performance improvement ideas, CI tools and measures need to be adapted to facilitate this integration. Relevant factors are analysed and their influences on CI measures are assessed.

Design/methodology/approach

The research approach is built upon an explorative case study supported by a comprehensive literature review. Empirical data were collected through participant observation, guided interviews and company documents.

Findings

The influences on employee involvement within CI programmes and the corresponding suitability of important CI measures were evaluated on a set of relevant factors. These factors include unique building projects, project-based focus on order fulfilment, fragmented order fulfilment process, separation of order fulfilment activities in terms of space and time, procedural rules for dealing with on-site failures, short-term contracts with subcontractors and the practice of evaluating and monitoring performance on site.

Research limitations/implications

The research paves the way for the development of suitable tools, measures and methods to effectively involve employees from all profession within a CI programme in IHB. The empirical part of this research is based on a single case study.

Originality/value

This work extends the body of knowledge of CI application in the construction industry with an analysis of factors influencing its implementation and management.
Wideband performance limitations of the C-FDTD in the discretization impoverishment of a curved surface
Authors: Fortes Lucas Lobo Latorre , Gonçalves Sandro Trindade Mordente
Published: June 2020

Purpose

This paper aims to explore the limitations of the conformal finite difference time-domain method (C-FDTD or Dey–Mittra) when modeling perfect electric conducting (PEC) and lossless dielectric curved surfaces in coarse meshes. The C-FDTD is a widely known approach to reduce error of curved surfaces in the FDTD method. However, its performance limitations are not broadly described in the literature, which are explored as a novelty in this paper.

Design/methodology/approach

This paper explores the C-FDTD method applied on field scattering simulations of two curved surfaces, a dielectric and a PEC sphere, through the frequency range from 0.8 to 10 GHz. For each sphere, the mesh was progressively impoverished to evaluate the accuracy drop and performance limitations of the C-FDTD with the mesh impoverishment, along with the wideband frequency range described.

Findings

This paper shows and quantifies the C-FDTD method’s accuracy drops as the mesh is impoverished, reducing C-FDTD’s performance. It is also shown how the performance drops differently according to the frequency of interest.

Practical implications

With this study, coarse meshes, with smaller execution time and reduced memory usage, can be further explored reliably accounting the desired accuracy, enabling a better trade-off between accuracy and computational effort.

Originality/value

This paper quantifies the limitations of the C-FDTD in coarse meshes in a wideband manner, which brings a broader and newer insight upon C-FDTD’s limitations in coarse meshes or relatively small objects in electromagnetic simulation.
Parameter identification of solar cells and fuel cell using improved social spider algorithm
Authors: Kashefi Hadi , Sadegheih Ahmad , Mostafaeipour Ali , Mohammadpour Omran Mohammad
Published: June 2020

Purpose

To design, control and evaluate photovoltaic (PV) systems, an accurate model is required. Accuracy of PV models depends on model parameters. This study aims to use a new algorithm called improved social spider algorithm (ISSA) to detect model parameters.

Design/methodology/approach

To improve performance of social spider algorithm (SSA), an elimination period is added. In addition, at the beginning of each period, a certain number of the worst solutions are replaced by new solutions in the search space. This allows the particles to find new paths to get the best solution.

Findings

In this paper, ISSA is used to estimate parameters of single-diode and double-diode models. In addition, effect of irradiation and temperature on I–V curves of PV modules is studied. For this purpose, two different modules called multi-crystalline (KC200GT) module and polycrystalline (SW255) are used. It should be noted that to challenge the performance of the proposed algorithm, it has been used to identify the parameters of a type of widely used module of fuel cell called proton exchange membrane fuel cell. Finally, comparing and analyzing of ISSA results with other similar methods shows the superiority of the presented method.

Originality/value

Changes in the spider’s movement process in the SSA toward the desired response have improved the algorithm’s performance. Higher accuracy and convergence rate, skipping local minimums, global search ability and search in a limited space can be mentioned as some advantages of this modified method compared to classic SSA.
The relative decision-making algorithm for ranking data
Authors: Chen Yin-Ju , Lo Jian-Ming
Published: June 2020

Purpose

Decision-making is always an issue that managers have to deal with. Keenly observing to different preferences of the targets provides useful information for decision-makers who do not require too much information to make decisions. The main purpose is to avoid decision-makers in a dilemma because of too much or opaque information. Based on problem-oriented, this research aims to help decision-makers to develop a macro-vision strategy that fits the needs of different clusters of customers in terms of their favorite restaurants. This research also focuses on providing the rules to rank data sets for decision-makers to make choices for their favorite restaurant.

Design/methodology/approach

When the decision-makers need to rethink a new strategic planning, they have to think about whether they want to retain or rebuild their relationship with the old consumers or continue to care for new customers. Furthermore, many of the lecturers show that the relative concept will be more effective than the absolute one. Therefore, based on rough set theory, this research proposes an algorithm of related concepts and sends questionnaires to verify the efficiency of the algorithm.

Findings

By feeding the relative order of calculating the ranking rules, we find that it will be more efficient to deal with the faced problems.

Originality/value

The algorithm proposed in this research is applied to the ranking data of food. This research proves that the algorithm is practical and has the potential to reveal important patterns in the data set.
Workforce education diversity, work organization and innovation propensity
Authors: Bello-Pintado Alejandro , Bianchi Carlos
Published: June 2020

Purpose

Diversity of people, knowledge and resources has been identified as a determinant of firms' growth. This paper focusses on innovation propensity as a critical dimension of firm's growth path, aiming to analyse the effects of the firm's horizontal educational diversity (HED) on the propensity to conduct different technological innovation activities (TIAs). In addition, considering the evidence showing that these effects are neither direct nor linear, the authors analyse the moderating role of the firm's organizational practices oriented to knowledge sharing (KS) on the association between HED and the adoption of TIAs.

Design/methodology/approach

Following the theoretical arguments of the resource-based view (RBV), the evolutionary economics and the dynamic capabilities approach and related empirical evidences, the authors proposed four hypotheses regarding the effect of HED on TIAs and the moderating role of work organization practices oriented to promote KS. Empirically, the authors calculated different HED diversity indexes capturing two basic dimensions: variety and balance. Hence, using instrumental variables and panel data techniques to control endogeneity biases, the authors tested the proposed hypotheses using a data set of Uruguayan manufacturing firms between 2004 and 2015.

Findings

In line with previous evidence, results showed idiosyncratic context effects. The authors found a robust, linear, positive and significant relationship between HED and TIAs, but the effect can only be consistently associated with the adoption of internal or external research and development (R&D) activities. Moreover, the moderating role of work organization practices oriented to promote KS is positive and significant when firms engage in TIAs. For technological innovations that only involve the acquisiton of technology (AT), a positive effect is also observed but always associated to organizational practices oriented to promote KS.

Originality/value

This paper revisits the analysis of workforce diversity for a relatively less explored context. This research contributes to the field by linking HED and work organization practices to understand firm's innovation propensity in a developing context. Moreover, while other studies have focussed only on top management or R&D team diversity, the authors have analysed the whole professional's workforce. It allows the authors to discuss the effects of diversity on innovation propensity in the light of the ongoing debate on the effects of innovation in employment.
Exploring the effects of habit strength on scholarly publishing
Authors: Moksness Lars , Olsen Svein Ottar , Tuu Ho Huy
Published: June 2020

Purpose

This study aims to explore the role of habit strength in explaining intention and open access (OA) and non-OA scholarly publishing.

Design/methodology/approach

A decomposed theory of planned behaviour (TPB) is used as the conceptual framework to investigate a sample of 1,588 researchers from the major universities in Norway. Different latent construct models are analysed with a structural equation modelling approach.

Findings

The results show that the effect of habit was non-significant in an extended TPB framework where attitude was most important, followed by norms and perceived behavioural control in explaining intention to submit OA. Habit was only found to have a significant impact on intention to submit OA when it played a role as a full mediator for the effects of the intentional antecedents. In this modified model, norms were found to have a stronger effect than attitudes in explaining the habit to submit OA. OA habit strength forms intentions to publish in OA journals and reduces the intention to publish and publishing behaviour in NOA journals.

Research limitations/implications

Other individual forces (e.g. personality and personal values) and the role of habit strength should be included for future research.

Practical implications

The results provide empirical insights to management, policy makers and research on scholarly publishing.

Originality/value

This paper contributes not only to the understanding of OA scholarly publishing, but is also relevant for research on what drives (academic) data sharing, knowledge sharing, the sharing economy or the open source movement.
Professional artefacts: evaluating creative outcomes for work-based inquiry
Authors: Nottingham Paula McIver
Published: June 2020

Purpose

This paper aims to explore graduate perspectives about the creation and use of professional artefacts to communicate work-based inquiry projects to professional audiences.

Design/methodology/approach

The study was based on constructivist qualitative interviews with 14 graduates from a part-time professional practice in arts programme and used thematic analysis to interpret and discuss the findings.

Findings

Participants indicated a perceived value in the use of the professional artefact as a way of articulating their professional inquiry. Professional artefacts enable essential communication skills for professional contexts, have the capacity for engaging with professional audiences that are external to the university, have the potential for enabling further study and workplace employability, show awareness of project management and leadership capabilities and helped some individuals build on and share their own personal philosophy of practice with peer professionals.

Research limitations/implications

As a small-scale research project that used purposive sampling, the findings are not representative, but could provide the creative means to develop professional artefacts within work-related educational programmes and workplace learning programmes.

Practical implications

It is argued that the process and production of professional artefacts can provide the means for communicating work-based projects to professional audiences within workplace settings.

Originality/value

Professional artefacts explore and present developmental aspects of work-based inquiries with distinctive creative approaches to favour practice knowledge and innovation that can be expressively shared with peer professionals.
Educational tourism and experiential learning: students’ perceptions of field trips
Authors: Arcodia Charles , Abreu Novais Margarida , Cavlek Nevenka , Humpe Andreas
Published: June 2020

Purpose

This paper aims to investigate participants’ motivations and perceptions of a field trip. Specifically, this paper examines if and how students’ perceptions change with time and it explores the main factors for ensuring success in an experiential learning tourism program.

Design/methodology/approach

The study gathered and compared data collected in two points in time – immediately at the end of the experience and two months afterward. T-tests for paired samples were used to examine potential differences in perceptions and principal component analysis was used to identify the key factors determining the success of the experience.

Findings

The findings indicate that there are various motivations behind participation and that time barely affects perceptions of the experience. Furthermore, three factors emerged as important for meeting expectations, namely, social and professional connections, learning and traditional yet engaging teaching.

Research limitations/implications

While the outcomes are useful, they need to be thoughtfully applied because of the small data set. It is important to repeat similar investigations to allow more certainty in the propositions formulated. Furthermore, future studies should evaluate a broader variety of outcomes to determine whether perceptions remain constant. The implications are that educators and destination managers can easily apply these conclusions for the benefit and the findings can inform other field trips and broader experiential initiatives.

Originality/value

Despite research on learning outcomes and perceptions of experiential learning having expanded considerably, a fundamental question that remains unanswered is how perceptions of such experiences change and, consequently, when the most appropriate time is to assess participant perceptions.
Predicting medical tourism behavioural intention using social cognition models
Authors: Seow Ai Na , Choong Yuen Onn , Moorthy Krishna , Choong Chee Keong
Published: June 2020

Purpose

Few studies have adopted social psychology theories to understand the medical tourism decision-making process. The purpose of this study is to fill the said gap by suggesting the adoption of two social cognition models: the theory of planned behaviour (TPB) and protection motivation theory (PMT), to predict medical tourism behavioural intention, as well as compare their predictive power by integrating TBP and PMT in a single model.

Design/methodology/approach

A quantitative method has been adopted. There were 265 international tourists from various regions who visited Malaysia (one of the main medical tourism players in Asia), who were asked to complete the survey questionnaire. Data was analysed using the partial least squares structural equation modelling technique.

Findings

The results of this study provided support and validated the well-developed research models of TPB and PMT. Although PMT appears to be a more concrete and specific framework, the TPB model results have a slight advantage. TPB results emphasised the important roles of attitude, subjective norms and perceived behavioural control in developing behavioural intentions, and thus directly linked to the development of pull marketing strategies. PMT results emphasised the important roles of perceived threats and coping appraisal of health care in developing push strategies for medical tourism.

Originality/value

The research illustrates the need for rigorous examination of the ability of behavioural theories. The findings can aid in scrutinising their shortcomings and their readiness to modify, integrate and enhance in a more constructive manner when they address the health-education interventions, especially in a medical tourism context.
‘The Machine Stops’: E. M. Forster's Esoteric Critique of H. G. Wells’ A Modern Utopia
Authors: FLAHERTY SEAMUS
Published: June 2020

This article argues that E. M. Forster's dystopian science fiction story ‘The Machine Stops’ was conceived as a critique of H. G. Wells’ book, A Modern Utopia. The article shows how Forster responded to Wells’ utopia at almost every level. It demonstrates how the notion of making society function like a machine was an idea posited, if not implemented, by Wells. Forster sought to show how, rather than limiting pain, fear and anxiety, the machine‐society Wells envisaged would exacerbate all three. Forster regarded Wells a poor prognosticator of unintended consequences. On Forster's view, instead of a world of happy, healthy and vigorous citizens, Wells’ utopia foreshadowed a world of ill‐health and frustration. Instead of a world of variety and regular travel, Wells’ utopia foreshadowed a world of uniformity and stasis. Instead of a world of increased intelligence and personal initiative, Wells’ utopia foreshadowed a world of stupidity, credulity and lack of imagination. In ‘The Machine Stops’, Forster parodied Wells’ utopia, attacking Wells’ policy of state intervention in the family, his advocacy of euthanasia, his policy of expulsion and the details of everyday life in Wells’ utopia. In paying sustained attention to Forster's dystopia other scholars will recognise its intrinsic philosophical value. In its remarkable anticipation of technology resembling the internet, more than both Huxley's and Orwell's dystopia's, Forster's ‘The Machine Stops’ speaks directly to twenty‐first‐century predicaments.
Convergent cross‐sectional and longitudinal evidence for gaming‐cue specific posterior parietal dysregulations in early stages of internet gaming disorder
Authors: Yu Fangwen , Sariyska Rayna , Lachmann Bernd , Wang Qianqian , Reuter Martin , Weber Bernd , Trautner Peter , Yao Shuxia , Montag Christian , Becker Benjamin
Published: June 2020

Exaggerated reactivity to drug‐cues and emotional dysregulations represent key symptoms of early stages of substance use disorders. The diagnostic criteria for (Internet) gaming disorder strongly resemble symptoms for substance‐related addictions. However, previous cross‐sections studies revealed inconsistent results with respect to neural cue reactivity and emotional dysregulations in these populations. To this end, the present fMRI study applied a combined cross‐sectional and longitudinal design in regular online gamers (n = 37) and gaming‐naïve controls (n = 67). To separate gaming‐associated changes from predisposing factors, gaming‐naive subjects were randomly assigned to 6 weeks of daily Internet gaming or a non‐gaming condition. At baseline and after the training, subjects underwent an fMRI paradigm presenting gaming‐related cues and non‐gaming–related emotional stimuli. Cross‐sectional comparisons revealed gaming‐cue specific enhanced valence attribution and neural reactivity in a parietal network, including the posterior cingulate in regular gamers as compared to gaming naïve‐controls. Longitudinal analysis revealed that 6 weeks of gaming elevated valence ratings as well as neural cue‐reactivity in a similar parietal network, specifically the posterior cingulate in previously gaming‐naïve controls. Together, the longitudinal design did not reveal supporting evidence for altered emotional processing of non‐gaming associated stimuli in regular gamers whereas convergent evidence for increased emotional and neural reactivity to gaming‐associated stimuli was observed. Findings suggest that exaggerated neural reactivity in posterior parietal regions engaged in default mode and automated information processing already occur during early stages of regular gaming and probably promote continued engagement in gaming behavior.
Outcomes from intensive care in patients with COVID‐19: a systematic review and meta‐analysis of observational studies
Authors: Armstrong R. A. , Kane A. D. , Cook T. M.
Published: June 2020

The emergence of coronavirus disease 2019 (COVID‐19) has led to high demand for intensive care services worldwide. However, the mortality of patients admitted to the intensive care unit (ICU) with COVID‐19 is unclear. Here, we perform a systematic review and meta‐analysis, in line with PRISMA guidelines, to assess the reported ICU mortality for patients with confirmed COVID‐19. We searched MEDLINE, EMBASE, PubMed and Cochrane databases up to 31 May 2020 for studies reporting ICU mortality for adult patients admitted with COVID‐19. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from the ICU or death. The definition thus did not include patients still alive on ICU. Twenty‐four observational studies including 10,150 patients were identified from centres across Asia, Europe and North America. In‐ICU mortality in reported studies ranged from 0 to 84.6%. Seven studies reported outcome data for all patients. In the remaining studies, the proportion of patients discharged from ICU at the point of reporting varied from 24.5 to 97.2%. In patients with completed ICU admissions with COVID‐19 infection, combined ICU mortality (95%CI) was 41.6% (34.0–49.7%), I2 = 93.2%). Sub‐group analysis by continent showed that mortality is broadly consistent across the globe. As the pandemic has progressed, the reported mortality rates have fallen from above 50% to close to 40%. The in‐ICU mortality from COVID‐19 is higher than usually seen in ICU admissions with other viral pneumonias. Importantly, the mortality from completed episodes of ICU differs considerably from the crude mortality rates in some early reports.
The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5 years
Authors: Gudmundsdottir Anna , Broström Lina , Skiöld Beatrice , Källén Karin , Serenius Fredrik , Norman Mikael , Aden Ulrika , Bonamy Anna‐Karin Edstedt
Published: June 2020

Aim

This study investigated patent ductus arteriosus (PDA) treatment and neurodevelopmental outcomes when extremely preterm born children reached 6.5 years.

Method

Our cohort was 435 children with neonatal PDA treatment data and neurodevelopmental follow‐up data, born in 2004‐2007, who participated in the Extremely Preterm Infants in Sweden Study. Pharmacological or surgical PDA treatment and the age at PDA treatment, were investigated in relation to the risks of moderate to severe neurodevelopmental impairment (NDI) and full‐scale intelligence quotient (FSIQ) at 6.5 years.

Results

The children who received PDA drug treatment, including those who also had surgery, had the same risk of moderate to severe NDI or lower FSIQ as untreated children. However, children who had primary PDA surgery faced increased risks of NDI, with an adjusted incidence rate ratio of 1.62 (95% confidence interval [CI] 1.28‐2.06) and a lower adjusted mean difference FSIQ of −7.1 (95% CI −11 to −3.2). Surgery at less than 10 days of life was associated with a significantly increased risk of moderate to severe NDI and lower FSIQ than surgery after 20 days.

Conclusion

Drug treatment followed by deferred surgery appeared to be a safer option for extremely preterm infants severely affected by PDA.
The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ‐related proteins and identification of protein domain families
Authors: Rouka Erasmia , Gourgoulianni Natalia , Lüpold Stefan , Hatzoglou Chrissi , Gourgoulianis Konstantinos , Blanckenhorn Wolf U. , Zarogiannis Sotirios G.
Published: June 2020

The involvement of Septate Junctions (SJs) in critical cellular functions that extend beyond their role as diffusion barriers in the epithelia and the nervous system has made the fruit fly an ideal model for the study of human diseases associated with impaired Tight Junction (TJ) function. In this study, we summarized current knowledge of the Drosophila melanogaster SJ‐related proteins, focusing on their unconventional functions. Additionally, we sought to identify human orthologs of the corresponding genes as well as protein domain families. The systematic literature search was performed in PubMed and Scopus databases using relevant key terms. Orthologs were predicted using the DIOPT tool and aligned protein regions were determined from the Pfam database. 3‐D models of the smooth SJ proteins were built on the Phyre2 and DMPFold protein structure prediction servers. A total of 30 proteins were identified as relatives to the SJ cellular structure. Key roles of these proteins, mainly in the regulation of morphogenetic events and cellular signalling, were highlighted. The investigation of protein domain families revealed that the SJ‐related proteins contain conserved domains that are required not only for cell‐cell interactions and cell polarity but also for cellular signalling and immunity. DIOPT analysis of orthologs identified novel human genes as putative functional homologs of the fruit fly SJ genes. A gap in our knowledge was identified regarding the domains that occur in the proteins encoded by eight SJ‐associated genes. Future investigation of these domains is needed to provide functional information.
Intact vagal gut‐brain signalling prevents hyperphagia and excessive weight gain in response to high‐fat high‐sugar diet
Authors: McDougle Molly , Quinn Danielle , Diepenbroek Charlene , Singh Arashdeep , de la Serre Claire , de Lartigue Guillaume
Published: June 2020

Aim

The tools that have been used to assess the function of the vagus nerve lack specificity. This could explain discrepancies about the role of vagal gut‐brain signalling in long‐term control of energy balance. Here we use a validated approach to selectively ablate sensory vagal neurones that innervate the gut to determine the role of vagal gut‐brain signalling in the control of food intake, energy expenditure and glucose homoeostasis in response to different diets.

Methods

Rat nodose ganglia were injected bilaterally with either the neurotoxin saporin conjugated to the gastrointestinal hormone cholecystokinin (CCK), or unconjugated saporin as a control. Food intake, body weight, glucose tolerance and energy expenditure were measured in both groups in response to chow or high‐fat high‐sugar (HFHS) diet. Willingness to work for fat or sugar was assessed by progressive ratio for orally administered solutions, while post‐ingestive feedback was tested by measuring food intake after an isocaloric lipid or sucrose pre‐load.

Results

Vagal deafferentation of the gut increases meal number in lean chow‐fed rats. Switching to a HFHS diet exacerbates overeating and body weight gain. The breakpoint for sugar or fat solution did not differ between groups, suggesting that increased palatability may not drive HFHS‐induced hyperphagia. Instead, decreased satiation in response to intra‐gastric infusion of fat, but not sugar, promotes hyperphagia in CCK‐Saporin‐treated rats fed with HFHS diet.

Conclusions

We conclude that intact sensory vagal neurones prevent hyperphagia and exacerbation of weight gain in response to a HFHS diet by promoting lipid‐mediated satiation.
Similar safety and efficacy in previously treated adults with growth hormone deficiency randomized to once‐weekly somapacitan or daily growth hormone
Authors: Otsuka Fumio , Takahashi Yutaka , Tahara Shigeyuki , Ogawa Yoshihisa , Højby Rasmussen Michael , Takano Koji
Published: June 2020

Objective

Somapacitan is a long‐acting, reversible albumin‐binding growth hormone (GH) derivative in development. This study aimed to evaluate the safety and efficacy of once‐weekly somapacitan versus daily GH over 52 weeks in Japanese patients with adult growth hormone deficiency (AGHD).

Design

Phase 3, multicentre, randomized, parallel‐group, open‐label, active‐controlled trial (NCT03075644).

Patients

Previously GH‐treated Japanese patients with AGHD were randomized 3:1 to somapacitan (n = 46) or daily GH (n = 16) for 20 weeks’ dose titration and 32 weeks’ fixed‐dose treatment.

Measurements

Primary endpoint was the incidence of adverse events (AEs). Secondary endpoints included change from baseline to week 52 in visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT).

Results

Mean (SD) prescribed doses after titration were 1.780 (1.058) mg/week for somapacitan and 0.197 (0.083) mg/day for daily GH. Rate of AEs per 100 patient‐years was similar between arms (somapacitan, 312.7; daily GH, 309.8). Four AEs in the somapacitan arm were serious; none were considered treatment‐related. Mean insulin‐like growth factor‐I standard deviation score (IGF‐I SDS) was maintained from baseline in both arms. No significant differences were observed between arms for change from baseline to week 52 in VAT, SAT or TAT (estimated difference, somapacitan – daily GH [95% CI]: −1.74 [−18.13; 14.66], −11.53 [−35.54; 12.48] and − 12.85 [−47.31; 21.62] cm2, respectively).

Conclusions

Treatment in both groups was well tolerated, with no unexpected safety findings. Impact on adipose tissue was similar to somapacitan and daily GH in patients with AGHD. A short visual summary of our work is available at https://bit.ly/3946YNF.
Neural and non‐neural contributions to enhanced joint stiffness in children with cerebral palsy
Authors: Meskers Carel GM , Kwakkel Gert
Published: June 2020

This commentary is on the original article by Xu et al. on pages 1040–1046 of this issue.
Autonomous vehicles, human agency and the potential of urban life
Authors: Yeo Si Jie Ivin , Lin Weiqiang
Published: June 2020

Research on autonomous vehicles has hitherto been largely concerned with its technological infrastructure, and with the management of smart transport systems in urban space. While there is a growing body of work on the sociological perspectives of autonomous vehicles, it has tended to remain technocentric, focusing on how self‐driving innovations have an effect on cities and urban lives. By thinking through the notions of sensation, action, and encounter, this paper advances a reconceptualisation of autonomous vehicles that better accounts for human agency and sentience in an increasingly automated urban world. More broadly, this paper seeks to illuminate the emergent and creative potential of urban life to unsettle and complicate the taken‐for‐granted power of smart and autonomous technologies in enacting urban transformations.
Going private: Are private prisons cost‐saving options for states?
Authors: White Weston , Pena Anita Alves , Weiler Stephan
Published: June 2020

As prison populations have increased, states have often turned to private prisons in an effort to save on correctional costs. This paper first considers the trade‐offs between private and public prisons, then assesses the cost‐effectiveness of such strategies across all 50 states over 1999–2015 using a fixed‐effects panel model. We find that private prisons provide no significant systematic cost savings over the period of study, adding econometric clarification to previously inconclusive case study evidence.
Fault Seal Analysis in an Onshore Unconventional Gas Target, North Perth Basin
Authors: Mullen F. , Archer R. , Yielding G. , Boogaerdt H.
Published: June 2020

During the 1980s, hydrocarbons were logged in aquifers during drilling of conventional gas wells in the Woodada gasfield. The gasfield is located in the North Perth Basin in Western Australia. Using Fault Seal Analysis Technology, our goal was to test the hypothesis that faults in the Kockatea Shale that are currently being reactivated may be leak prone. Wells proximal to faults with a fracture stability of greater than 5 MPa logged only methane. Wells proximal to faults with a fracture stability ≤5 MPa logged both methane and condensate in aquifers confirming that hydrocarbon leakage is correlated with critically stressed faults. This assessment assumes that fault rocks in the Kockatea Shale, which is a regional source rock and seal, comprise uncemented phyllosilicate rock. For the normal stress case, faults oriented west‐north‐west with moderate dip have the lowest integrity. For the strike slip stress case, faults oriented north‐west and west‐south‐west, with moderate to steep dip have the lowest integrity. If the Kockatea Shale fault rock is assumed to be a cemented phyllosilicate, then the fracture stability increases to 14 MPa for both the normal and strike slip case. In this case, Jurassic‐Permian fault intersections may be contributing to hydrocarbon leakage, however, this would require numerical modeling for confirmation. Based on leak off tests, the increase in pressure required to hydraulically fracture the formation varies between 10.7 and 13.8 MPa. The treatment pressures used during hydraulic fracturing may potentially exacerbate leakage in areas such as the Woodada gasfield.
In vitro wear of dual‐cured bulkfill composites and flowable bulkfill composites
Authors: Roulet Jean‐François , Gummadi Snigdha , Hussein Hind S. , Abdulhameed Nader , Shen Chiayi
Published: June 2020

Objectives

The objective of this study is to test the wear of dual‐cured bulkfill and flowable bulkfill composites.

Materials and methods

Six dual‐cured bulkfill composites, Cention, Cention‐Exp, Activa, Fill‐up, Hyperfil Injectafill, and two flowable bulkfill composites Tetric Evoflow BulkFill and G‐aenial Universal Flo were tested in this study (n = 8). Each composite was applied into an aluminum sample holder and cured with a Valo Grand (1230 mW/cm2) or self‐cured according to manufacturer's recommendations, and stored in water for 3 weeks. The samples were subjected to 120 000 load cycles of 49 N (CS‐4) against spherical steatite antagonists and simultaneously subjected to 4440 thermocycles (5°C‐55°C). At intervals between load cycles, polyvinyl siloxane impressions were taken and scanned with a True Definition Laser Scanner. The volumetric wear was calculated using image software (Geomagic). Microscopic images of selected wear facets and their corresponding worn antagonists were obtained using SEM. All data were analyzed using analysis of variance (ANOVA) and Tukey post hoc test for multiple comparison (α = .05; β = .2).

Results

The load cycles volumetric wear‐increase was linear. Two‐way ANOVA showed significant main effects (material and light‐cured) and significant interactions. Self‐cured materials (mean = 0.38 mm3) showed more wear than light‐cured materials (mean = 0.35mm3).

Conclusions

The bioactive materials except Activa light‐cured showed significantly more wear than the flowable composites.

Clinical significance

This study demonstrated that most of the dual‐cured composites, if light‐cured, showed the same wear as the flowable composites used as control. Therefore, to obtain adequate wear resistance the dual‐cured composites should be routinely light‐cured.
Responses of triacylglycerol synthesis in Skeletonema marinoi to nitrogen and phosphate starvations
Authors: Zhang Mei , Xing Yongze , Wang Fuwen , Mi Tiezhu , Zhen Yu
Published: June 2020

Skeletonema marinoi is one of the most widespread marine planktonic diatoms in temperate coastal regions and sometimes can form massive blooms. Yet, the molecular mechanisms of triacylglycerol (TAG) synthesis in nutrient‐deficient conditions for this species are still unknown. This study aimed to investigate how the TAG biosynthetic pathway of S. marinoi reacts to the culture age and nitrogen (N) or phosphorus (P) deficiency at molecular levels. Meanwhile, we also described the physiological and biochemical changes of S. marinoi in response to N or P starvation over time. To obtain reliable qRT‐PCR data, six putative reference genes were identified for assessing expression stability using geNorm and BestKeeper software, and Actin exhibited the most stable expression across 45 tested S. marinoi samples. We found that the expression of TAG biosynthesis‐related genes and ACCase enzyme activity varied in response to the different nutrient conditions and culture age. Taken together, we speculated that the capacity of TAG biosynthesis in S. marinoi is induced by N or P stress, and increases with culture age. Furthermore, TAG biosynthesis appears to respond more strongly to P deficiency than to N deficiency. Our study provides important insights into how diatoms regulate the TAG biosynthetic pathway when stressed by nutrient limitation. Besides, the data obtained from this study also provide useful clues for further exploring genes that can be used for metabolic engineering to enhance lipid production.