bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Frailty and Depression Among Community-Dwelling Older Adults: The Mediating and Moderating Role of Social Support
Authors: Jin Yaru , Si Huaxin , Qiao Xiaoxia , Tian Xiaoyu , Liu Xinyi , Xue Qian-Li , Wang Cuili
Published: June 2020

Background and Objectives

Frailty is associated with depression in older adults and reduces their social support. However, the mechanism underlying such relationship remains unclear. We aim to examine whether social support acts as a mediator or moderator in the relationship between frailty and depression.

Research Design and Methods

This cross-sectional study was conducted among 1,779 community-dwelling older adults aged 60 and older. Frailty, social support, and depressive symptoms were measured by the Physical Frailty Phenotype, Social Support Rating Scale, and five-item Geriatric Depression Scale, respectively. Data were also collected on age, gender, years of schooling, monthly income, cognitive function, number of chronic diseases, physical function, and pain.

Results

Linear regression models showed that subjective support and support utilization, but not objective support, mediated and moderated the relationship between frailty and depressive symptoms. The Johnson–Neyman technique determined a threshold of 30 for subjective support, but not for support utilization, beyond which the detrimental effect of frailty on depressive symptoms was offset.

Discussion and Implications

Social support underlies the association of frailty with depression, and its protective role varies by type. Interventions on depression should address improving perceptions and utilization of social support among frail older adults rather than simply providing them with objective support.
Galactic Circos: User-friendly Circos plots within the Galaxy platform
Authors: Rasche Helena , Hiltemann Saskia
Published: June 2020

Background

Circos is a popular, highly flexible software package for the circular visualization of complex datasets. While especially popular in the field of genomic analysis, Circos enables interactive graphing of any analytical data, including alternative scientific domain data and non-scientific data. This high degree of flexibility also comes with a high degree of complexity, which may present an obstacle for researchers not trained in programming or the UNIX command line. The Galaxy platform provides a user-friendly browser-based graphical interface incorporating a broad range of “wrapped” command line tools to facilitate accessibility.

Findings

We have developed a Galaxy wrapper for Circos, thus combining the power of Circos with the accessibility and ease of use of the Galaxy platform. The combination substantially simplifies the specification and configuration of Circos plots for end users while retaining the power to produce publication-quality visualizations of complex multidimensional datasets.

Conclusions

Galactic Circos enables the creation of publication-ready Circos plots using only a web browser, via the Galaxy platform. Users may download the full set of Circos configuration files of their plots for further manual customization. This version of Circos is available as an open-source installable application from the Galaxy ToolShed, with its use clarified in a training manual hosted by the Galaxy Training Network.
An Autonomous EU Functionality Doctrine for Shape Exclusions
Authors: Suthersanen Uma , Mimler Marc D
Published: June 2020

Exclusionary subject matter are often underpinned by public interest considerations. In the case of shapes of products, the Court of Justice of the European Union has aligned the interpretation of the relevant exclusionary provisions within design and trade mark laws. More recently, European jurisprudence within copyright law in relation to conditions of protection has imported the same considerations so as to regulate the protection of shapes of products. This article explores the multitude of doctrinal and policy reasons underpinning shape exclusions and argues that the Court is consciously creating an EU autonomous functionality doctrine within intellectual property law. We also argue that the Court is building a European macro-rationale within these laws namely to ensure that protection does not unduly restrict market freedom and competition.
Delivering a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: a descriptive costing study
Authors: Ansbro Éimhín , Garry Sylvia , Karir Veena , Reddy Amulya , Jobanputra Kiran , Fardous Taissir , Sadique Zia
Published: June 2020

The Syrian conflict has caused enormous displacement of a population with a high non-communicable disease (NCD) burden into surrounding countries, overwhelming health systems’ NCD care capacity. Médecins sans Frontières (MSF) developed a primary-level NCD programme, serving Syrian refugees and the host population in Irbid, Jordan, to assist the response. Cost data, which are currently lacking, may support programme adaptation and system scale up of such NCD services. This descriptive costing study from the provider perspective explored financial costs of the MSF NCD programme. We estimated annual total, per patient and per consultation costs for 2015–17 using a combined ingredients-based and step-down allocation approach. Data were collected via programme budgets, facility records, direct observation and informal interviews. Scenario analyses explored the impact of varying procurement processes, consultation frequency and task sharing. Total annual programme cost ranged from 4 to 6 million International Dollars (INT$), increasing annually from INT$4 206 481 (2015) to INT$6 739 438 (2017), with costs driven mainly by human resources and drugs. Per patient per year cost increased 23% from INT$1424 (2015) to 1751 (2016), and by 9% to 1904 (2017), while cost per consultation increased from INT$209 to 253 (2015–17). Annual cost increases reflected growing patient load and increasing service complexity throughout 2015–17. A scenario importing all medications cut total costs by 31%, while negotiating importation of high-cost items offered 13% savings. Leveraging pooled procurement for local purchasing could save 20%. Staff costs were more sensitive to reducing clinical review frequency than to task sharing review to nurses. Over 1000 extra patients could be enrolled without additional staffing cost if care delivery was restructured. Total costs significantly exceeded costs reported for NCD care in low-income humanitarian contexts. Efficiencies gained by revising procurement and/or restructuring consultation models could confer cost savings or facilitate cohort expansion. Cost effectiveness studies of adapted models are recommended.
Break Down the Silos: A Conceptual Framework on Multisectoral Approaches to the Prevention and Control of Vector-Borne Diseases
Authors: Zhong Qingxia , Fouque Florence
Published: June 2020

The need for multisectoral approaches (MSAs) in prevention and control of vector-borne diseases (VBDs) has been identified. VBD programs often involve collaborations between health and nonhealth sectors; however, a systematic framework describing the process, requirements, challenges, and benefits of MSAs has been missing. A recent guidance document from UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases provides a framework to implement MSAs for prevention and control of VBDs. This article gives an introduction to the guidance document and describes the conceptual framework and coordination process. The next steps will be to test the framework through implementation research in specific VBD cases studies. The guidance document will thus be refined based on iterative and comprehensive monitoring and evaluation systems to assess the performance and impact of MSAs. The advocacy for MSA and necessary capacity building will be integrated into the testing of the framework.
Methylated derivatives of l-tyrosine in reaction catalyzed by l-amino acid oxidase: isotope and inhibitory effects
Authors: Pająk Małgorzata
Published: June 2020

l-Amino acid oxidase (LAAO) is widely distributed in nature and shows important biological activity. It induces cell apoptosis and has antibacterial properties. This study was designed to investigate the effect of methyl substituent on its activity as methylated derivatives of l-tyrosine, labelled with short-lived B+ emitters, have been used in oncological diagnostics. To study isotope effects in the oxidative deamination of O-methyl-l-tyrosine, the deuterated isotopomer, i.e. O-methyl-[2-2H]-l-tyrosine, was synthesized by isotope exchange, catalyzed enzymatically by tryptophanase. Isotope effects were determined using the spectrophotometric non-competitive method. The values of isotope effects indicate that the α-C–H bond cleavage occurs in the rate determining step of the investigated reaction and α-hydrogen plays a role in the substrate binding process at the enzyme active site. The inhibitory effect on LAAO activity was studied with α-methyl-l-tyrosine and N-methyl-l-tyrosine. The mode of inhibition was determined based on Lineweavear–Burk plots intersections. α-Methyl-l-tyrosine has been found a mixed type inhibitor of the investigated enzyme, whereas N-methyl-l-tyrosine is a non-competitive inhibitor of LAAO.
Do Preschoolers’ Neuropsychological Functioning and Hyperactivity/Inattention Predict Social Functioning Trajectories Through Childhood?
Authors: Karlsberg Bennett Jenna , O’Neill Sarah , Rajendran Khushmand , Halperin, Jeffrey M
Published: June 2020

Objective

This longitudinal study examined whether preschool attention deficit hyperactivity disorder (ADHD) symptoms and neuropsychological functioning predicted trajectories of children’s social functioning from age 3 to 4 through 12 years.

Methods

Three- and four-year-old children (N = 208; 72.6% boys) were evaluated annually through age 12. Parent and teacher Attention Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition responses during the initial evaluation were used to categorize preschoolers as “High” or “Low” risk for ADHD. Children’s neuropsychological functioning was assessed using the NEPSY. Teachers’ reports of children’s social functioning were obtained annually from preschool through age 12 years using the Adaptability, Functional Communication, and Social Skills subscales of the Behavioral Assessment System for Children, Second Edition. Hierarchical linear modeling was used to assess the trajectories of social functioning and determine whether preschoolers’ neuropsychological functioning and ADHD risk status predicted social functioning at age 12 years, and/or change in social functioning throughout childhood. All models controlled for baseline socioeconomic status.

Results

High Risk children had significantly lower teacher-rated Adaptability and Social Skills at age 12 years. High Risk children and those with lower Verbal neuropsychological functioning in preschool had lower teacher-rated Functional Communication at 12 years old. Lower preschool Verbal neuropsychological functioning predicted greater positive change in teacher-rated Functional Communication across childhood.

Conclusions

Early identification of and intervention for children exhibiting ADHD behaviors is critical given the enduring negative impact of these behaviors on social functioning. Screening preschoolers for verbal difficulties is encouraged given their long-term impact on children’s ability to clearly express thoughts and feelings and obtain and provide information.
Diagnosing gastric volvulus in chest X-ray: report of three cases
Authors: Pandit Narendra , Kumar Abhijeet , Yadav Tek Narayan , Irfan Qamar Alam , Gautam Sujan , Awale Laligen
Published: June 2020

Gastric volvulus is a rare abnormal rotation of the stomach along its axis. It is a surgical emergency, hence requires prompt diagnosis and treatment to prevent life-threatening gangrenous changes. Hence, a high index of suspicion is required in any patients presenting with an acute abdomen in emergency. The entity can present acutely with pain abdomen and vomiting, or as chronic with non-specific symptoms. Chest X-ray findings to diagnose it may be overlooked in patients with acute abdomen. Here, we report three patients with gastric volvulus, where the diagnosis was based on the chest X-ray findings, confirmed with computed tomography, and managed successfully with surgery.
Novel PKD1 Mutations in Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Kim Hyerin , Kim Hyung-Hoi , Chang Chulhun L , Song Sang Heon , Kim Namhee
Published: June 2020

Objective

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease. Identifying mutated causative genes can provide diagnostic and prognostic information. In this study, we describe the clinical application of a next generation sequencing (NGS)-based, targeted multi-gene panel test for the genetic diagnosis of patients with ADPKD.

Methods

We applied genetic analysis on 26 unrelated known or suspected patients with ADPKD. A total of 10 genes related to cystic change of kidney were targeted. Detected variants were classified according to standard guidelines.

Results

We identified 19 variants (detection rate: 73.1%), including PKD1 (n = 18) and PKD2 (n = 1). Of the 18 PKD1 variants, 8 were novel.

Conclusion

Multigene panel test can be a comprehensive tool in a clinical setting for genetic diagnosis of ADPKD. It allows us to identify clinically significant novel variants and confirm the diagnosis, and these objectives are difficult to achieve using conventional diagnostic tools.
Oscillations of a coronal plasma slab excited by an external source
Authors: Lopin I , Nagorny I
Published: June 2020

The dispersive properties of fast oscillations in a coronal plasma slab are studied. These oscillations are assumed to be generated by an external source, located at a finite distance from the slab. It is shown that the problem reduces to examination of the normal modes of a system, consisting of a slab cavity and a finitely distant rigid boundary. The relation that governs the eigenfrequencies of the system is derived. Both the kink and the sausage modes are excited. The main finding indicates that the principal kink mode is trapped not for all axial wavenumbers. It has a non-zero cut-off wavenumber and can exist either as a trapped mode or as a leaky mode. This cut-off tends to zero for infinitely distant sources, in accordance with the well-known result from the normal mode analysis. The expressions for the frequency and damping rate of the leaky principal kink mode are derived. The effect of a finitely distant rigid boundary on the higher transverse-order kink modes and all the sausage modes is found to be only minor, when the distance between the source and the slab is much more than the transverse size of the slab. The applications of the obtained results in coronal seismology are discussed.
The Pristine Inner Galaxy Survey (PIGS) II: Uncovering the most metal-poor populations in the inner Milky Way
Authors: Arentsen Anke , Starkenburg Else , Martin Nicolas F , Aguado David S , Zucker Daniel B , Allende Prieto Carlos , Hill Vanessa , Venn Kim A , Carlberg Raymond G , González Hernández Jonay I , Mashonkina Lyudmila I , Navarro Julio F , Sánchez-Janssen Rubén , Schultheis Mathias , Thomas Guillaume F , Youakim Kris , Lewis Geraint F , Simpson Jeffrey D , Wan Zhen , Cohen Roger E , Geisler Doug , O’Connell Julia E
Published: June 2020

Metal-poor stars are important tools for tracing the early history of the Milky Way, and for learning about the first generations of stars. Simulations suggest that the oldest metal-poor stars are to be found in the inner Galaxy. Typical bulge surveys, however, lack low metallicity ($\rm {[Fe/H]} \lt -1.0$) stars because the inner Galaxy is predominantly metal-rich. The aim of the Pristine Inner Galaxy Survey (PIGS) is to study the metal-poor and very metal-poor (VMP, $\rm {[Fe/H]} \lt -2.0$) stars in this region. In PIGS, metal-poor targets for spectroscopic follow-up are selected from metallicity-sensitive CaHK photometry from the CFHT. This work presents the ∼250 deg2 photometric survey as well as intermediate-resolution spectroscopic follow-up observations for ∼8000 stars using AAOmega on the AAT. The spectra are analysed using two independent tools: ULySS with an empirical spectral library, and FERRE with a library of synthetic spectra. The comparison between the two methods enables a robust determination of the stellar parameters and their uncertainties. We present a sample of 1300 VMP stars – the largest sample of VMP stars in the inner Galaxy to date. Additionally, our spectroscopic data set includes ∼1700 horizontal branch stars, which are useful metal-poor standard candles. We furthermore show that PIGS photometry selects VMP stars with unprecedented efficiency: 86 per cent/80 per cent (lower/higher extinction) of the best candidates satisfy $\rm {[Fe/H]} \lt -2.0$, as do 80 per cent/63 per cent of a larger, less strictly selected sample. We discuss future applications of this unique data set that will further our understanding of the chemical and dynamical evolution of the innermost regions of our Galaxy.
Isochrone fitting of Galactic globular clusters – II. NGC 6205 (M13)
Authors: Gontcharov George A , Khovritchev Maxim Yu , Mosenkov Aleksandr V
Published: June 2020

We present new isochrone fits to colour–magnitude diagrams of the Galactic globular cluster NGC 6205 (M13). We utilize 34 photometric bands from the ultraviolet to mid-infrared by use of data from the HST, Gaia DR2, SDSS, unWISE, Pan-STARRS DR1, and other photometric sources. In our isochrone fitting we use the PARSEC, MIST, DSEP, BaSTI, and IAC-BaSTI theoretical models and isochrones, both for the solar-scaled and He–α-enhanced abundances, with a metallicity of about [Fe/H] = −1.58 adopted from the literature. The colour–magnitude diagrams, obtained with pairs of filters from different datasets but of similar effective wavelengths, show some colour offsets up to 0.04 mag between the fiducial sequences and isochrones. We attribute these offsets to systematic differences of the datasets. Some intrinsic systematic differences of the models/isochrones remain in our results: the derived distances and ages are different for the ultraviolet, optical and infrared photometry used, while the derived ages are different for the different models/isochrones, e.g. in the optical range from 12.3 ± 0.7 Gyr for He–α-enhanced DSEP to 14.4 ± 0.7 Gyr for MIST. Despite the presence of multiple stellar populations, we obtain convergent estimates for the dominant population: best-fitting distance 7.4 ± 0.2 kpc, true distance modulus 14.35 ± 0.06 mag, parallax 0.135 ± 0.004 mas, extinction AV = 0.12 ± 0.02, and reddening E(B − V) = 0.04 ± 0.01. These estimates agree with other recent estimates; however, the extinction and reddening are twice as high as generally accepted. The derived empirical extinction law agrees with the Cardelli–Clayton–Mathis extinction law with the best-fitting $R_\mathrm{V}=3.1^{+1.6}_{-1.1}$.
Synteny-Guided Resolution of Gene Trees Clarifies the Functional Impact of Whole-Genome Duplications
Authors: Parey Elise , Louis Alexandra , Cabau Cédric , Guiguen Yann , Roest Crollius Hugues , Berthelot Camille
Published: June 2020

Whole-genome duplications (WGDs) have major impacts on the evolution of species, as they produce new gene copies contributing substantially to adaptation, isolation, phenotypic robustness, and evolvability. They result in large, complex gene families with recurrent gene losses in descendant species that sequence-based phylogenetic methods fail to reconstruct accurately. As a result, orthologs and paralogs are difficult to identify reliably in WGD-descended species, which hinders the exploration of functional consequences of WGDs. Here, we present Synteny-guided CORrection of Paralogies and Orthologies (SCORPiOs), a novel method to reconstruct gene phylogenies in the context of a known WGD event. WGDs generate large duplicated syntenic regions, which SCORPiOs systematically leverages as a complement to sequence evolution to infer the evolutionary history of genes. We applied SCORPiOs to the 320-My-old WGD at the origin of teleost fish. We find that almost one in four teleost gene phylogenies in the Ensembl database (3,394) are inconsistent with their syntenic contexts. For 70% of these gene families (2,387), we were able to propose an improved phylogenetic tree consistent with both the molecular substitution distances and the local syntenic information. We show that these synteny-guided phylogenies are more congruent with the species tree, with sequence evolution and with expected expression conservation patterns than those produced by state-of-the-art methods. Finally, we show that synteny-guided gene trees emphasize contributions of WGD paralogs to evolutionary innovations in the teleost clade.
How a Scorpion Toxin Selectively Captures a Prey Sodium Channel: The Molecular and Evolutionary Basis Uncovered
Authors: Zhu Shunyi , Gao Bin , Peigneur Steve , Tytgat Jan
Published: June 2020

The growing resistance of insects to chemical pesticides is reducing the effectiveness of conventional methods for pest control and thus, the development of novel insecticidal agents is imperative. Scorpion toxins specific for insect voltage-gated sodium channels (Navs) have been considered as one of the most promising insecticide alternatives due to their host specificity, rapidly evoked toxicity, biodegradability, and the lack of resistance. However, they have not been developed for uses in agriculture and public health, mainly because of a limited understanding of their molecular and evolutionary basis controlling their phylogenetic selectivity. Here, we show that the traditionally defined insect-selective scorpion toxin LqhIT2 specifically captures a prey Nav through a conserved trapping apparatus comprising a three-residue-formed cavity and a structurally adjacent leucine. The former serves as a detector to recognize and bind a highly exposed channel residue conserved in insects and spiders, two major prey items for scorpions; and the latter subsequently seizes the “moving” voltage sensor via hydrophobic interactions to reduce activation energy for channel opening, demonstrating its action in an enzyme-like manner. Based on the established toxin-channel interaction model in combination with toxicity assay, we enlarged the toxic spectrum of LqhIT2 to spiders and certain other arthropods. Furthermore, we found that genetic background-dependent cavity shapes determine the species selectivity of LqhIT2-related toxins. We expect that the discovery of the trapping apparatus will improve our understanding of the evolution and design principle of Nav-targeted toxins from a diversity of arthropod predators and accelerate their uses in pest control.
Spotlight commentary: REBUS and the anarchic brain
Authors: Noorani Tehseen , Alderson-Day Ben
Published: June 2020

In ‘REBUS and the Anarchic Brain: Towards a Unified Model of the Brain Action of Psychedelics’, Carhart-Harris and Friston offer an important analysis of what the predictive processing framework has to offer our understanding of psychedelic experiences, providing an invaluable ground for psychedelic psychiatry. While applauding this, we encourage paying greater attention to contextual factors shaping extreme experiences and their sequalae, and suggest that the authors’ comparisons with certain non-psychedelic altered states may overlook more informative parallels that can be drawn elsewhere. Addressing both points will prove fruitful, ultimately, in identifying the mechanisms of action of greatest interest in psychedelic experiences.
Clinical Course of Unilateral Moyamoya Disease
Authors: Church Ephraim W , Bell-Stephens Teresa E , Bigder Mark G , Gummidipundi Santosh , Han Summer S , Steinberg Gary K
Published: June 2020

BACKGROUND

The natural history of unilateral moyamoya disease (MMD) progressing to bilateral MMD remains an enigma in modern vascular neurosurgery. Few, small series with limited follow-up have reported relatively high rates of contralateral stenosis progression.

OBJECTIVE

To review our large series of unilateral MMD patients and evaluate radiographic and surgical progression rates, and identify any factors associated with progression.

METHODS

We included all unilateral MMD cases treated from 1991 to 2017 in an observational study. We examined time to contralateral radiographic progression and contralateral progression requiring surgery. Using Cox regression analysis, we evaluated factors potentially associated with contralateral progression.

RESULTS

There were 217 patients treated for unilateral MMD. About 71% were female, and the average age at first surgery was 33.8 yr. Average follow-up was 5.8 yr (range 1-22 yr). A total of 18 patients (8.3%) developed contralateral progression. And 8 of these (3.7%) developed progression requiring bypass surgery. Baseline stenosis and hyperlipidemia (HLD) were significantly associated with radiographic progression (hazard ratio [HR] = 9.7, P = .006; HR = 4.0, P = .024). Baseline stenosis was associated with surgical progression (HR = 44.2, P = .002). Results were similar when controlling for possible confounders using multivariate regression.

CONCLUSION

Previous series showed relatively high rates of progression in unilateral MMD (15%-30%), but these studies were small and long-term follow-up was rarely available. Our large series indicates that the rate of progression is lower than previously reported but still warrants yearly noninvasive screening. These data may provide indirect support for statin therapy in MMD.
Re-Thinking Procedural Justice Theory Through Stop and Search: Shame, Anger, and Police Legitimacy
Authors: Scrase Stuart
Published: June 2020

Stop and search has been argued to have a damaging impact upon trust in police and compliance with the law. Procedural Justice Theory has sought to explain this relation through perceptions of (un)fairness leading to the production of (il)legitimacy and to dispositions to (dis)obey. The article proposes a theoretical framework to supplement an explanatory gap in this theory, namely why perceptions of unfairness might lead to anti-police dispositions or attitudes. Ethnographic research is employed to elucidate the relevance of affective, emotional, and cognitive mechanisms in relation to the practice of stop and search. The article argues that the normative representation of the suspect by police and the disempowerment or removal of the subject’s agency at the hands of police contain the capacity to reveal a disparity between self-understanding and social recognition: the central affective condition for shame. Transformations of this affective experience into anger defend self-esteem by positioning the police as at fault, questioning the claim to authority, and simultaneously constructing the expressive drive to mistrust and confront the goal-obstacle to self-esteem.
The psychological impact of COVID-19 on the mental health in the general population
Authors: Serafini G , Parmigiani B , Amerio A , Aguglia A , Sher L , Amore M
Published: June 2020

As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.
Diagnosis and treatment of patients with antiphospholipid syndrome: a mixed-method evaluation of care in The Netherlands
Authors: Klein Haneveld Mirthe J , Lemmen Caro H C , Brunekreef Tammo E , Bijl Marc , Jansen A J Gerard , de Leeuw Karina , Spierings Julia , Limper Maarten ,   ARCH Study Group, Lely Titia , van der Molen Renate , Urbanus Rolf , Kruyt Nyika , van de Ree Marcel , Potjewijd Judith , Brandts Gerie , Scheerhoorn-Pullen Jamy , de Bresser Carolijn , Otter Sander , Berentschot Julia , Hulsebosch Nicole , Schriemer Rita
Published: June 2020

Objectives

The aims were to gain insight into the care provided to patients with APS in The Netherlands and to identify areas for improvement from the perspective of both patients and medical specialists.

Methods

APS care was evaluated using qualitative and quantitative methods. Perspectives on APS care were explored using semi-structured interviews with medical specialists, patient focus groups and a cross-sectional, online patient survey. In order to assess current practice, medical records were reviewed retrospectively to collect data on clinical and laboratory manifestations and pharmacological treatment in six Dutch hospitals.

Results

Fourteen medical specialists were interviewed, 14 patients participated in the focus groups and 79 patients completed the survey. Medical records of 237 patients were reviewed. Medical record review showed that only one-third of patients were diagnosed with APS within 3 months after entering specialist care. The diagnostic approach and management varied between centres and specialists. Almost 10% of all patients and 7% of triple-positive patients with thrombotic APS were not receiving any anticoagulant treatment at the time of medical record review. Correspondingly, poor recognition and fragmentation of care were reported as the main problems by medical specialists. Additionally, patients reported the lack of accessible, reliable patient education, psychosocial support and trust in physicians as important points for improvement.

Conclusion

Delayed diagnosis, variability in management strategies and fragmentation of care were important limitations of APS care identified in this study. A remarkable 10% of patients did not receive any anticoagulant treatment.
The role of aspirin in the primary prevention of accelerated atherosclerosis in systemic autoimmune rheumatic diseases
Authors: Fasano Serena , Iacono Daniela , Riccardi Antonella , Ciccia Francesco , Valentini Gabriele
Published: June 2020

Aspirin is the most commonly used medication worldwide. Beside its well-known anti-inflammatory effects, a role has emerged in the prevention of cardiovascular events. However, a significant benefit has been demonstrated in secondary cardiovascular prevention only, while there is limited evidence supporting a role in primary prevention. This discrepancy might depend on the that so far, the high-risk populations that will achieve the greatest benefits yet experiencing minimal harmful side effects have not been identified. Patients with autoimmune systemic rheumatic diseases have an increased risk of cardiovascular complications compared with the general population, which makes aspirin of potential value in these subjects. Moving from general aspects of aspirin pharmacology and specific issues in general population, the aim of this study is to review the evidence about the role of low-dose aspirin in primary cardiovascular prevention in autoimmune systemic rheumatic diseases.
Classifying and diagnosing systemic lupus erythematosus in the 21st century
Authors: Aringer Martin , Johnson Sindhu R
Published: June 2020

The EULAR/ACR 2019 classification criteria for SLE constitute a current and optimized clinical approach to SLE classification. Classification is still not based on molecular approaches and the results from large studies using polyomics may be interpreted as demonstrating the relevance of the genetic and environmental background rather than splitting SLE into several entities. In fact, an association study within the EULAR/ACR classification criteria project found associations between manifestations only within organ domains. This independency of various organ manifestations argues for SLE as one disease entity. The current review article will therefore concentrate on the clinical and immunological manifestations of SLE and on what we have already learned in this century. Moreover, the structure and essential rules of the EULAR/ACR 2019 classification criteria will be discussed. While classification and diagnosis are distinct concepts, which have to remain clearly separated, information derived from the process towards the classification criteria is also useful for diagnostic purposes. Therefore this article also tries to delineate what classification can teach us for diagnosis, covering a wide variety of SLE manifestations.
First-line csDMARD monotherapy drug retention in psoriatic arthritis: methotrexate outperforms sulfasalazine
Authors: Jacobs Marleen E , Pouw Juliëtte N , Welsing Paco , Radstake Timothy R D J , Leijten Emmerik F A
Published: June 2020

Objectives

Conventional synthetic DMARDs (csDMARDs) are the first-line treatment for PsA, but there is conflicting data regarding their efficacy and scarce reports describing the duration of use (drug retention) of csDMARD in this population. Their position in treatment recommendations is a matter of growing debate due to the availability of alternative treatment options with higher levels of evidence. We aimed to study drug retention and predictors for drug retention among PsA patients receiving first-line csDMARD monotherapy.

Methods

Retrospective cohort study in DMARD-naïve adult PsA patients in whom a first csDMARD was prescribed as monotherapy primarily to treat PsA-related symptoms. The main outcome was time to failure of the csDMARD (i.e. stopping the csDMARD or adding another DMARD).

Results

A total of 187 patients were included, who were mainly prescribed MTX (n = 163) or SSZ (n = 21). The pooled median drug retention time was 31.8 months (interquartile range 9.04–110). Drug retention was significantly higher in MTX (median 34.5 months; interquartile range 9.60–123) as compared with SSZ-treated patients (median 12.0 months; interquartile range 4.80– 55.7) (P =0.016, log-rank test). In multivariable Cox regression, the use of MTX and older age were associated with increased retention. The main reasons for treatment failure were inefficacy (52%) and side effects (28%). Upon failure, MTX treated patients were more commonly, subsequently treated with a biologic DMARD compared with SSZ (P < 0.05).

Conclusion

MTX outperforms SSZ as a first-line csDMARD in DMARD-naïve PsA patients with respect to monotherapy drug retention in daily clinical practice.
Replication of Associations With Psychotic-Like Experiences in Middle Childhood From the Adolescent Brain Cognitive Development (ABCD) Study
Authors: Karcher Nicole R , Loewy Rachel L , Savill Mark , Avenevoli Shelli , Huber Rebekah S , Simon Tony J , Leckliter Ingrid N , Sher Kenneth J , Barch Deanna M
Published: June 2020

The fields of psychology and psychiatry are increasingly recognizing the importance of replication efforts. The current study aimed to replicate previous findings examining the construct validity and psychometric properties of a psychotic-like experiences (PLEs) measure in middle childhood using an independent subset of the baseline Adolescent Brain Cognitive Development (ABCD) sample. Using a remainder baseline sample of 7013 nine- to eleven-year-old children with complete data, we examined measurement invariance across race/ethnicity and sex, and examined the associations between the Prodromal Questionnaire Brief-Child Version (PQ-BC) and other measures of PLEs, internalizing symptoms, neuropsychological test performance, and developmental milestones, to determine whether previously obtained results replicated in this nonoverlapping baseline sample subset. The results replicated measurement invariance across ethnicity and sex, and analyses again found higher PQ-BC scores for African American (β = .364, 95% CI = 0.292, 0.435) and Hispanic (β = .255, 95% CI = 0.185, 0.324) groups. We also replicated that higher PQ-BC scores were associated with psychosis risk measures, higher rates of child-reported internalizing symptoms (Distress: β = .378, 95% CI = 0.357,0.398), neuropsychological test performance deficits (eg, working memory; Distress: β = −.069, 95% CI = −0.096, −0.042), and motor (Distress: β = .026, 95% CI = 0.003, 0.049) and speech (Distress: β = .042, 95% CI = 0.018, 0.065) developmental milestone delays. The current results replicated many findings from the original study examining the PQ-BC. We replicated evidence for mean differences in race/ethnicity, and associations with other PLE measures, greater internalizing symptoms, cognitive impairments, and developmental milestone delays. These findings indicate robust and reliable associations between PLEs and hypothesized correlates can be found in middle childhood nonclinical samples.
Developments affecting New Hampshire foundations
Authors: Mayo Todd D
Published: June 2020

In 2018, New Hampshire’s legislature established a study committee charged with re-evaluating the state’s laws governing foundations, trusts, and trust companies. After a series of hearings, the committee generally affirmed the integrity of those laws but recommended a handful of legislative changes. Some of those changes will potentially affect licensed private trust companies, including those organized as foundations. Meanwhile, a set of proposed technical corrections to the Foundation Act remain abeyant.
Diversity of Soil Bacterial Community Is Influenced by Spatial Location and Time but Not Potato Cultivar
Authors: Nahar Kamrun , Floc’h Jean-Baptiste , Goyer Claudia , Zebarth Bernie J. , Whitney Sean
Published: June 2020

Potato cultivars susceptible to common scab were previously reported to harbor five to six times more abundant pathogenic Streptomyces spp. in the rhizosphere soils compared with tolerant cultivars. It is still unclear if the diversity of soil bacterial communities is related to the abundance of pathogenic Streptomyces spp. This study evaluated the effects of potato cultivar on the diversity of bacterial communities in three spatial locations (soil located close to the plant [SCP], in the rhizosphere soil [RS], and in the geocaulosphere soil [GS]) in 2013 and 2014. Common scab tolerant (Goldrush and Hindenburg) and susceptible cultivars (Green Mountain and Agria) were planted in a field infested with pathogenic Streptomyces spp. causing common scab. The β-diversity of the bacterial community was significantly different between years and on dates within each year according to a permutational multivariate analysis of variance. The β-diversity also varied significantly among spatial locations (i.e., SCP, RS, and GS), probably due to changes in soil properties, but did not change significantly among potato cultivars. The architecture of the bacterial network in RS in 2014 was more complex compared with 2013 with a 2.5-fold increase in the number of bacteria included according to a co-occurrence analysis. These results indicated that the soil bacterial community diversity changed temporally and spatially. However, bacterial community diversity and richness were not affected by potato cultivar, suggesting that there were no relationships between bacterial community diversity or richness and the abundance of pathogenic Streptomyces spp.
Pediatric Sepsis Definition—A Systematic Review Protocol by the Pediatric Sepsis Definition Taskforce
Authors: Menon Kusum , Schlapbach Luregn J. , Akech Samuel , Argent Andrew , Chiotos Kathleen , Chisti Mohammod Jobayer , Hamid Jemila , Ishimine Paul , Kissoon Niranjan , Lodha Rakesh , Oliveira Cláudio Flauzino , Peters Mark , Tissieres Pierre , Watson R. Scott , Wiens Matthew O. , Wynn James L. , Sorce Lauren R.
Published: June 2020

Objectives:

Sepsis is responsible for a substantial proportion of global childhood morbidity and mortality. However, evidence demonstrates major inaccuracies in the use of the term “sepsis” in clinical practice, coding, and research. Current and previous definitions of sepsis have been developed using expert consensus but the specific criteria used to identify children with sepsis have not been rigorously evaluated. Therefore, as part of the Society of Critical Care Medicine’s Pediatric Sepsis Definition Taskforce, we will conduct a systematic review to synthesize evidence on individual factors, clinical criteria, or illness severity scores that may be used to identify children with infection who have or are at high risk of developing sepsis-associated organ dysfunction and separately those factors, criteria, and scores that may be used to identify children with sepsis who are at high risk of progressing to multiple organ dysfunction or death.

Data Sources:

We will identify eligible studies by searching the following databases: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials.

Study Selection:

We will include all randomized trials and cohort studies published between January 1, 2004, and March 16, 2020.

Data Extraction:

Data extraction will include information related to study characteristics, population characteristics, clinical criteria, and outcomes.

Data Synthesis:

We will calculate sensitivity and specificity of each criterion for predicting sepsis and conduct a meta-analysis if the data allow. We will also provide pooled estimates of overall hospital mortality.

Conclusions:

The potential risk factors, clinical criteria, and illness severity scores from this review which identify patients with infection who are at high risk of developing sepsis-associated organ dysfunction and/or progressing to multiple organ dysfunction or death will be used to inform the next steps of the Pediatric Sepsis Definition Taskforce.
Effect of a Recombinant Human Soluble Thrombomodulin on Baseline Coagulation Biomarker Levels and Mortality Outcome in Patients With Sepsis-Associated Coagulopathy
Authors: Levi Marcel , Vincent Jean-Louis , Tanaka Kosuke , Radford Amanda H. , Kayanoki Toshihiko , Fineberg David A. , Hoppensteadt Debra , Fareed Jawed
Published: June 2020

Objectives:

To assess the effects of recombinant human soluble thrombomodulin treatment on 28-day all-cause mortality in subgroups categorized by baseline coagulation biomarker levels (prothrombin fragment 1.2, thrombin-antithrombin complex, d-dimer) in patients with sepsis-associated coagulopathy in the Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin trial (SCARLET) (NCT01598831).

Design:

Post hoc, subgroup analysis of a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study.

Setting:

ICUs at 159 sites in 26 countries.

Patients:

Eight-hundred adults with sepsis-associated coagulopathy defined as international normalized ratio greater than 1.40 and platelet count between 30 × 109/L and 150 × 109/L or greater than 30% decrease within 24 hours with concomitant cardiovascular and/or respiratory failure.

Interventions:

Patients randomized and treated with recombinant human soluble thrombomodulin (0.06 mg/kg/d; n = 395) or equivalent placebo (n = 405) for 6 days.

Measurements and Main Results:

Recombinant human soluble thrombomodulin did not significantly reduce 28-day all-cause mortality in the Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin trial: absolute risk reduction was 2.55% (p = 0.32) in patients with sepsis-associated coagulopathy. In this post hoc analysis, mortality steadily increased with increasing baseline prothrombin fragment 1.2 and thrombin-antithrombin complex levels in the placebo group; for those values exceeding the upper limit of normal, the mortality increases in the recombinant human soluble thrombomodulin group were lower or negligible with increasing baseline prothrombin fragment 1.2 and thrombin-antithrombin complex. Consequently, absolute risk reductions were greater in subgroups with higher baseline prothrombin fragment 1.2 or thrombin-antithrombin complex. Absolute risk reductions were also greater in subgroups with baseline coagulation biomarker levels at or above median of the entire study population, ranging from 4.2% (95% CI, –5.0% to 13.4%) to 5.5% (95% CI, –4.0% to 14.9%).

Conclusions:

Compared with patients receiving placebo, patients treated with recombinant human soluble thrombomodulin having higher baseline thrombin generation biomarker levels had lower mortality. Further research regarding the predictive role of coagulation biomarkers for recombinant human soluble thrombomodulin treatment response in sepsis-associated coagulopathy is warranted to evaluate clinical relevance.
INDUCTION OF POSTERIOR VITREOUS DETACHMENT IN PEDIATRIC PATIENTS BY RADIAL PERIFOVEAL STRIPPING
Authors: Patel Nimesh A. , Berrocal Audina M.
Published: June 2020

Background/Purpose:

In certain cases, there may be firm adherence of the cortical vitreous to the retinal surface during pars plana vitrectomy. This report aims to present an alternative method of posterior vitreous detachment (PVD) induction at the macula with the use of a flexible loop.

Methods:

A 5-year-old girl underwent 25-gauge pars plana vitrectomy for optic pit maculopathy. Triamcinolone is used for staining. Posterior vitreous detachment was induced in the perifoveal area with 360° radial peeling. The vitrector was then used to lift and complete the PVD.

Results:

Posterior vitreous detachment was able to be induced with minimal trauma to the retinal surface. There were no postoperative complications from the procedure.

Conclusion:

Posterior vitreous detachment induction at the macula using a flexible loop and radial stripping is a safe and reliable alternative to conventional techniques.
Lack of sufficient public space can limit the effectiveness of COVID-19’s social distancing measures
Authors: Nobajas Alexandre , Ganau i Casas Joan , Paül i Agustí Daniel , Peacock Adam
Published: June 2020

One of the primary strategies of slowing down the COVID-19 pandemic has been the establishment of social distancing rules that recommend keeping a buffer distance between individuals, and this has proven effective in helping in reducing the basic reproduction number [R 0]1. However, social distancing rules have put the use of public spaces in densely populated places under strain, and this is especially important as some of the most virulent outbreaks of the COVID-19 pandemic have been in compact cities. It is therefore fundamental to take into account each neighbourhood’s morphological characteristics and the potential population densities each street, square or park can accommodate under such new regulations in order to effectively enforce social distancing rules. Otherwise, certain areas may be rapidly overwhelmed by crowds with citizens unable to maintain the minimum safe distance between individuals. In this paper, we develop a method to identify the potential public space accessibility if social distancing rules are followed and we apply it to three global and highly affected by COVID-19 cities. Our research finds that, at micro level there are important inequalities between neighbourhoods, so people will struggle to comply with social distancing rules and consequently it will make controlling infection rates more difficult.