bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation research on measuring quality in primary care: balancing national needs with learning from the Eastern Mediterranean Region
Authors: LETAIEF MONDHER , Hirschhorn Lisa R , Leatherman Sheila , Sayed Alaa A , Sheikh Aziz , Siddiqi Sameen
Published: August 2021

Background

Universal Health Coverage (UHC) is a core element of ensuring healthy lives, marking the third Sustainable Development Goal. It requires providing quality primary health-care (PHC) services. Assessment of quality of care considering a wide variety of contexts is a challenge. This study lists practical indicators to enhance the quality of PHC.

Objectives

Demonstrating quality indicators for PHC that are feasible, comprehensive and adaptable to wide array of health systems and resource settings.

Methods

We applied the research framework: Exploration, Preparation, Implementation and Sustainment. Exploration included a scoping review to identify quality indicators. Preparation included an eDelphi to refine the primary indicators’ list. A panel of 27 experts reviewed the list that was later pilot tested in PHC facilities. The outcomes were presented to two further expert consultations, to refine indicators and plan for broader testing. Implementation included testing the indicators through a five-step process in 40 facilities. A regional consultation in May 2016 discussed the testing outcomes.

Results

Initial efforts identified 83 quality indicators at the PHC level that were then refined to a 34-indicator list covering the six domains of quality. A toolkit was also developed to test the feasibility of each indicator measurement, data availability, challenges and gaps. Pilot testing provided insight into modifying and adding some indicators. Wide variability was encountered within and in between facilities, and timely initiation of antenatal care, for example, ranged 31–90% in Oman and 11–98% in Tunisia. Indicators were highly feasible, and 29 out of 34 were measured in 75% of facilities or more. While challenges included gaps in capacity for data collection, the tool showed high adaptability to the local context and was adopted by countries in the Eastern Mediterranean Region (EMR) including Libya, Oman, Iran, Pakistan, Sudan and Palestine. Stakeholders agreed on the high relevance and applicability of the proposed indicators that have been used to inform improvement.

Conclusion

A cross-regional set of 34 quality indicators of PHC in the EMR was developed and adopted by a diverse group of countries. The toolkit showed high feasibility in pilot testing reflecting the practicality needed to encourage local uptake and sustainability. The core quality indicators are highly adaptable to different local and regional contexts regardless of current PHC strength or available resources. Continuous evaluation and sharing lessons of implementation and use are needed to ascertain the indicators’ effectiveness in driving improvements in PHC and to refine and strengthen the evidence supporting the set of indicators for wider adoption.
Another Geopolitics? International Relations and the Boundaries of World Order
Authors: Burles Regan
Published: August 2021

Geopolitics has become a key site for articulating the limits of existing theories of international relations and exploring possibilities for alternative political formations that respond to the challenges posed by massive ecological change and global patterns of violence and inequality. This essay addresses three recent books on geopolitics in the age of the Anthropocene: Simon Dalby's Anthropocene Geopolitics: Globalization, Security, Sustainability (2020), Jairus Victor Grove's Savage Ecology: War and Geopolitics at the End of the World (2019), and Bruno Latour's Down to Earth: Politics in the New Climactic Regime (2018). The review outlines and compares how these authors pose contemporary geopolitics as a problem and offer political ecology as the ground for an alternative geopolitics. The essay considers these books in the context of critiques of world politics in international relations to shed light on both the contributions and the limits of political ecological theories of global politics. I argue that the books under review encounter problems and solutions posed in Kant's critical and political writings in relation to the concepts of epigenesis and teleology. These provoke questions about the ontological conceptions of order that enable claims to world political authority in the form of a global international system coextensive with the earth's surface.
Crohn’s and Colitis Canada’s 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Executive Summary
Authors: Ellen Kuenzig M , Windsor Joseph W , Barrett Lisa , Bernstein Charles N , Bitton Alain , Carroll Matthew W , Chauhan Usha , Coward Stephanie , Fowler Sharyle , Ghia Jean-Eric , Geist Rose , Gibson Deanna L , Graff Lesley A , Griffiths Anne M , Guoxian Huang James , Jones Jennifer L , Khanna Reena , Lakatos Peter L , Lee Kate , Mack David R , Marshall John K , Mukhtar Mariam S , Murthy Sanjay K , Nguyen Geoffrey C , Panaccione Remo , Seow Cynthia H , Singh Harminder , Tandon Parul , Targownik Laura E , Zelinsky Sandra , Benchimol Eric I , Kaplan Gilaad G
Published: August 2021

Persons with inflammatory bowel disease (IBD) make up more than 0.75% of the Canadian population in 2021. Early in the COVID-19 pandemic, individuals with IBD, particularly those on immunosuppressive therapies, were concerned that their health status may place them at higher risk of contracting COVID-19 or experiencing more severe disease course if infected with SARS-CoV-2. In response, Crohn’s and Colitis Canada developed the COVID-19 and IBD Taskforce in March 2020 to rapidly synthesize the evolving knowledge of COVID-19 as relevant to Canadians with IBD. The Taskforce communicated expert information directly to the Canadian IBD community through online tools and a webinar series. In order to understand the full impact of COVID-19 on the IBD community, Crohn’s and Colitis Canada commissioned a policy report that was informed through a systematic literature review and synthesized across working groups along the following domains: Epidemiology, Children and Expectant Mothers with IBD, Seniors with IBD, Mental Health, Risk Factors and Medications, Vaccines, and Healthcare Delivery during the Pandemic and the Future Model of IBD Care. This report from Canadian physicians, researchers, and IBD community representatives highlights the physical, mental, and health systems impact of COVID-19 on the entire spectrum of the IBD community, including children, adolescents, adults, seniors, and pregnant people with IBD. This executive summary provides an overview of the crucial information from each of the chapters of the policy report, supplemented with additional information made available through Crohn’s and Colitis Canada’s webinar-based knowledge translation platform.
Crohn’s and Colitis Canada’s 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Health Care Delivery During the Pandemic and the Future Model of Inflammatory Bowel Disease Care
Authors: Jones Jennifer L , Benchimol Eric I , Bernstein Charles N , Huang James Guoxian , Marshall John K , Mukhtar Mariam S , Murthy Sanjay K , Nguyen Geoffrey C , Kaplan Gilaad G , Kuenzig M Ellen , Tandon Parul , Targownik Laura E , Windsor Joseph W , Bitton Alain
Published: August 2021

The SARS-CoV-2 pandemic has had a profound impact on inflammatory bowel disease (IBD) health care delivery. The implementation of necessary public health restrictions has restricted access to medications, procedures and surgeries throughout the pandemic, catalyzing widespread change in how IBD care is delivered. Rapid large-scale implementation of virtual care modalities has been shown to be feasible and acceptable for the majority of individuals with IBD and health care providers. The SARS-CoV-2 pandemic has exacerbated pre-existing barriers to accessing high-quality, multidisciplinary IBD care that addresses health care needs holistically. Continued implementation and evaluation of both synchronous and asynchronous eHealthcare modalities are required now and in the future in order to determine how best to incorporate these modalities into patient-centred, collaborative care models. Resources must be dedicated to studies that evaluate the feasibility, acceptability and effectiveness of eHealth-enhanced models of IBD care to improve efficiency and cost-effectiveness, while increasing quality of life for persons living with IBD. Crohn’s and Colitis Canada will continue to play a major leadership role in advocating for the health care delivery models that improve the quality of life for persons living with IBD.
Current status and future perspectives of immunotherapy against urothelial and kidney cancer
Authors: Kobayashi Takashi , Takeuchi Ario , Nishiyama Hiroyuki , Eto Masatoshi
Published: August 2021

Much attention has been paid to immune checkpoint inhibitors to various cancer treatments. In urothelial cancer, pembrolizumab was initially approved for patients who either recurred or progressed following platinum-based chemotherapy. For the platinum-fit population, although the standard first-line treatment is still platinum-based systemic chemotherapy, avelumab has been recently approved as a maintenance therapy for patients who have not had disease progression with four to six cycles of first-line chemotherapy. In addition, adjuvant nivolumab has just prolonged disease-free survival (DFS) by ~10 months, compared with placebo in patients with muscle-invasive bladder urothelial cancer or upper tract urothelial cancer at high-risk of recurrence after radical surgical resection.

On the other hand, in kidney cancer, nivolumab was initially approved for advanced renal cell carcinoma patients after one or two prior anti-angiogenic therapies. Next, combinations of two immune checkpoint inhibitors (nivolumab + ipilimumab) and immune checkpoint inhibitor + tyrosine kinase inhibitors (pembrolizumab + axitinib and avelumab + axitinib) were approved for the first-line treatment for patients with advanced renal cell carcinoma. Recently, new generation tyrosine kinase inhibitors, such as cabozantinib and lenvatinib have been combined with immune checkpoint inhibitors. Both nivolumab + cabozantinib and pembrolizumab + lenvatinib have demonstrated superior progression-free survival and objective response rate, compared with sunitinib. So far, no prospective trials have demonstrated the duration of immune checkpoint inhibitor treatments. We are now doing the Japan Clinical Oncology Group 1905 trial, where patients with advanced renal cell carcinoma who have received an immune checkpoint inhibitor for 24 weeks are divided into two groups: those who continue immune checkpoint inhibitor treatment and those who discontinue immune checkpoint inhibitor treatment.
A universal relationship between stellar masses and binding energies of galaxies
Authors: Shi Yong , Yu Xiaoling , Mao Shude , Gu Qiusheng , Xia Xiaoyang , Chen Yanmei
Published: August 2021

In this study, we demonstrate that stellar masses of galaxies (Mstar) are universally correlated through a double power-law function with the product of the dynamical velocities (Ve) and sizes to one-fourth power ($R_{\rm e}^{0.25}$) of galaxies, both measured at the effective radii. The product $V_{\rm e}R_{\rm e}^{0.25}$ represents the fourth root of the total binding energies within effective radii of galaxies. This stellar mass-binding energy correlation has an observed scatter of 0.14 dex in log($V_{\rm e}R_{\rm e}^{0.25}$) and 0.46 dex in log(Mstar). It holds for a variety of galaxy types over a stellar mass range of nine orders of magnitude, with little evolution over cosmic time. A toy model of self-regulation between binding energies and supernovae feedback is shown to be able to reproduce the observed slopes, but the underlying physical mechanisms are still unclear. The correlation can be a potential distance estimator with an uncertainty of 0.2 dex independent of the galaxy type.
Dust in RCW 58: Clues to common envelope channel formation?
Authors: Jiménez-Hernández P , Arthur S J , Toalá J A , Marston A P
Published: August 2021

We present a characterization of the dust in the Wolf–Rayet (WR) nebula RCW 58 around the WN8h star WR 40 using archival infrared (IR) observations from WISE and Herschel and radio observations from ATCA. We selected two clumps, free from contamination from material along the line of sight and located towards southern regions in RCW 58, as representative of the general properties of this WR nebula. Their optical, IR, and radio properties are then modelled using the photoionization code cloudy, which calculates a self-consistent spatial distribution of dust and gas properties. Two populations of dust grains are required to model the IR SED: a population of small grains with sizes 0.002–0.01 $\mu$m, which is found throughout the clumps, and a population of large grains, with sizes up to 0.9 $\mu$m, located further from the star. Moreover, the clumps have very high dust-to-gas ratios, which present a challenge for their origin. Our model supports the hypothesis that RCW 58 is distributed in a ring-like structure rather than a shell, and we estimate a mass of ∼2.5 M⊙. This suggests that the mass of the progenitor of WR 40 was about $\approx 40^{+2}_{-3}$ M⊙. The ring morphology, low nebular mass, large dust grain size, and high dust-to-gas ratio lead us to propose that RCW 58 has formed through a common envelope channel, similar to what has been proposed for M 1-67.
Strong gravitational lens image of the M87 black hole with a simple accreting matter model
Authors: Boero Ezequiel F , Moreschi Osvaldo M
Published: August 2021

We study simulated images generated from an accretion disc surrounding the supermassive black hole hosted in the nearby galaxy M87. We approach the problem employing very simple accreting models inspired from magnetohydrodynamical simulations and introducing a new recipe for dealing with the combined integration of the geodesic and geodesic deviation equations in Kerr space–time, which allows for a convenient and efficient way to manage the system of equations. The geometry of the basic emission model is given by a two-temperature thin disc in the equatorial plane of the black hole supplemented by an asymmetric bar structure. We show that this configuration permits to generate the most salient features appearing in the EHT Collaboration images of M87 with impressive fidelity.
SDSS-IV MaNGA: Stellar M/L gradients and the M/L-colour relation in galaxies
Authors: Ge Junqiang , Mao Shude , Lu Youjun , Cappellari Michele , Long Richard J , Yan Renbin
Published: August 2021

The stellar mass-to-light ratio gradient in SDSS r-band ∇(M*/Lr) of a galaxy depends on its mass assembly history, which is imprinted in its morphology and gradients of age, metallicity, and stellar initial mass function (IMF). Taking a MaNGA sample of 2051 galaxies with stellar masses ranging from 109 to 1012M⊙ released in SDSS DR15, we focus on face-on galaxies, without merger and bar signatures, and investigate the dependence of the 2D ∇(M*/Lr) on other galaxy properties, including M*/Lr-colour relationships by assuming a fixed Salpeter IMF as the mass normalization reference. The median gradient is ∇M*/Lr ∼ −0.1 (i.e. the M*/Lr is larger at the centre) for massive galaxies, becomes flat around M* ∼ 1010M⊙ and change sign to ∇M*/Lr ∼ 0.1 at the lowest masses. The M*/Lr inside a half-light radius increases with increasing galaxy stellar mass; in each mass bin, early-type galaxies have the highest value, while pure-disc late-type galaxies have the smallest. Correlation analyses suggest that the mass-weighted stellar age is the dominant parameter influencing the M*/Lr profile, since a luminosity-weighted age is easily affected by star formation when the specific star formation rate (sSFR) inside the half-light radius is higher than 10−3 Gyr−1. With increased sSFR gradient, one can obtain a steeper negative ∇(M*/Lr). The scatter in the slopes of M*/L-colour relations increases with increasing sSFR, for example, the slope for post-starburst galaxies can be flattened to 0.45 from the global value 0.87 in the M*/L versus g − r diagram. Hence converting galaxy colours to M*/L should be done carefully, especially for those galaxies with young luminosity-weighted stellar ages, which can have quite different star formation histories.
Noncoding Variation and Transcriptional Plasticity Promote Thermal Adaptation in Oysters by Altering Energy Metabolism
Authors: Li Ao , Li Li , Zhang Ziyan , Li Shiming , Wang Wei , Guo Ximing , Zhang Guofan
Published: August 2021

Genetic variation and phenotypic plasticity are both important to adaptive evolution. However, how they act together on particular traits remains poorly understood. Here, we integrated phenotypic, genomic, and transcriptomic data from two allopatric but closely related congeneric oyster species, Crassostrea angulata from southern/warm environments and Crassostrea gigas from northern/cold environments, to investigate the roles of genetic divergence and plasticity in thermal adaptation. Reciprocal transplantation experiments showed that both species had higher fitness in their native habitats than in nonnative environments, indicating strong adaptive divergence. The southern species evolved higher transcriptional plasticity, and the plasticity was adaptive, suggesting that increased plasticity is important for thermal adaptation to warm climates. Genome-wide comparisons between the two species revealed that genes under selection tended to respond to environmental changes and showed higher sequence divergence in noncoding regions. All genes under selection and related to energy metabolism exhibited habitat-specific expression with genes involved in ATP production and lipid catabolism highly expressed in warm/southern habitats, and genes involved in ATP consumption and lipid synthesis were highly expressed in cold/northern habitats. The gene for acyl-CoA desaturase, a key enzyme for lipid synthesis, showed strong selective sweep in the upstream noncoding region and lower transcription in the southern species. These results were further supported by the lower free fatty acid (FFA) but higher ATP content in southern species and habitat, pointing to significance of ATP/FFA trade-off. Our findings provide evidence that noncoding variation and transcriptional plasticity play important roles in shaping energy metabolism for thermal adaptation in oysters.
Evidence for complex dynamics during U2 snRNP selection of the intron branchpoint
Authors: Kao Ching-Yang , Cao En-Cih , Wai Hsu Lei , Cheng Soo-Chen
Published: August 2021

Splicing of pre-mRNA is initiated by binding of U1 to the 5′ splice site and of Msl5-Mud2 heterodimer to the branch site (BS). Subsequent binding of U2 displaces Msl5-Mud2 from the BS to form the prespliceosome, a step governing branchpoint selection and hence 3′ splice site choice, and linking splicing to myelodysplasia and many cancers in human. Two DEAD-box proteins, Prp5 and Sub2, are required for this step, but neither is stably associated with the pre-mRNA during the reaction. Using BS-mutated ACT1 pre-mRNA, we previously identified a splicing intermediate complex, FIC, which contains U2 and Prp5, but cannot bind the tri-snRNP. We show here that Msl5 remains associated with the upstream cryptic branch site (CBS) in the FIC, with U2 binding a few bases downstream of the BS. U2 mutants that restore U2-BS base pairing enable dissociation of Prp5 and allows splicing to proceed. The CBS is required for splicing rescue by compensatory U2 mutants, and for formation of FIC, demonstrating a role for Msl5 in directing U2 to the BS, and of U2-BS base pairing for release of Prp5 and Msl5-Mud2 to form the prespliceosome. Our results provide insights into how the prespliceosome may form in normal splicing reaction.
ESA1 regulates meiotic chromosome axis and crossover frequency via acetylating histone H4
Authors: Wang Ying , Zhai Binyuan , Tan Taicong , Yang Xiao , Zhang Jiaming , Song Meihui , Tan Yingjin , Yang Xuan , Chu Tingting , Zhang Shuxian , Wang Shunxin , Zhang Liangran
Published: August 2021

Meiotic recombination is integrated into and regulated by meiotic chromosomes, which is organized as loop/axis architecture. However, the regulation of chromosome organization is poorly understood. Here, we show Esa1, the NuA4 complex catalytic subunit, is constitutively expressed and localizes on chromatin loops during meiosis. Esa1 plays multiple roles including homolog synapsis, sporulation efficiency, spore viability, and chromosome segregation in meiosis. Detailed analyses show the meiosis-specific depletion of Esa1 results in decreased chromosome axis length independent of another axis length regulator Pds5, which further leads to a decreased number of Mer2 foci, and consequently a decreased number of DNA double-strand breaks, recombination intermediates, and crossover frequency. However, Esa1 depletion does not impair the occurrence of the obligatory crossover required for faithful chromosome segregation, or the strength of crossover interference. Further investigations demonstrate Esa1 regulates chromosome axis length via acetylating the N-terminal tail of histone H4 but not altering transcription program. Therefore, we firstly show a non-chromosome axis component, Esa1, acetylates histone H4 on chromatin loops to regulate chromosome axis length and consequently recombination frequency but does not affect the basic meiotic recombination process. Additionally, Esa1 depletion downregulates middle induced meiotic genes, which probably causing defects in sporulation and chromosome segregation.
Taxonomic and functional differences between winter and summer crustacean zooplankton communities in lakes across a trophic gradient
Authors: Shchapov K , Wilburn P , Bramburger A J , Silsbe G M , Olmanson L , Crawford C J , Litchman E , Ozersky T
Published: August 2021

Despite increasing interest in winter limnology, few studies have examined under-ice zooplankton communities and the factors shaping them in different types of temperate lakes. To better understand drivers of zooplankton community structure in winter and summer, we sampled 13 lakes across a large trophic status gradient for crustacean zooplankton abundance, taxonomic and functional community composition and C/N stable isotopes. Average winter zooplankton densities were one-third of summer densities across the study lakes. Proportionally, cladocerans were more abundant in summer than winter, with the opposite pattern for calanoids and cyclopoids. In green (eutrophic) lakes, zooplankton densities were higher under the ice than in brown (dystrophic) and blue (oligotrophic) lakes, suggesting better conditions for zooplankton in productive lakes during winter. Overall, zooplankton communities were more similar across lakes under the ice than during the open water season. Feeding group classification showed a decrease in herbivore abundance and an increase in predators from summer to winter. C/N stable isotope results suggested higher lipid content in overwintering zooplankton and potentially increased reliance on the microbial loop by winter zooplankton. Our results show substantial variation in the seasonality of zooplankton communities in different lake types and identify some of the factors responsible for this variation.
The impact of the COVID-19 pandemic on the number of presentations of penetrating injuries to a UK major trauma centre
Authors: Hickland Maria M , Massouh Philippa , Sutthakorn Roxanne E , Greenslade Charlotte , Jennings Cara , Cantle Fleur , Bew Duncan
Published: August 2021

Background

Knife-related violence is of growing concern in the UK. This study aims to investigate the impact of the COVID-19 pandemic on the frequency of penetrating injuries at a UK major trauma centre.

Methods

This was a retrospective study comparing the number of patients attending the emergency department of King’s College Hospital (KCH) with a penetrating injury (gunshot or stab wound) during the ‘pandemic year’ (1 March 2020–28 February 2021) compared with the equivalent time period in the previous year. Penetrating injuries as a result of self-harm were excluded. The primary outcome was to assess whether there were any changes to the frequency of presentations during three periods of national lockdowns.

Results

Lockdown 1 showed a 48.45% reduction in presentations in the ‘pandemic year’ compared to the previous year, lockdown 2 showed a 31.25% reduction; however, lockdown 3 showed an 8.89% increase in the number of presentations.

Conclusion

Our findings suggest that despite the initial reduction in the number of presentations of penetrating injury during lockdown 1, this returned to normal levels by lockdown 3. Further research is required to understand the effects of government-imposed restrictions on interpersonal violence and identify appropriate methods of outreach prevention during a pandemic.
Individual-level and country-level socio-economic factors and health outcomes in spondyloarthritis: analysis of the ASAS-perSpA study
Authors: Capelusnik Dafne , Zhao Sizheng Steven , Boonen Annelies , Ziade Nelly , Medina Clementina López , Dougados Maxime , Nikiphorou Elena , Ramiro Sofia
Published: August 2021

Objectives

The aim of this study was to investigate the association between individual-level and country-level socio-economic (SE) factors and health outcomes across SpA phenotypes.

Methods

Patients with axial SpA (axSpA), peripheral SpA (pSpA) or PsA from the ASAS-perSpA study (in 23 countries) were included. The effect of individual-level (age, gender, education and marital status) and country-level [e.g. Gross Domestic Product (GDP)] SE factors on health outcomes [Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.1, ASDAS, BASFI, fatigue and the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI)] was assessed in mixed-effects models adjusted for potential confounders. Interactions between SE factors and disease phenotype were tested. A mediation analysis was conducted to explore whether the impact of country-level SE factors on ASDAS was mediated through biologic/targeted synthetic (b/ts) DMARD uptake.

Results

In total, 4185 patients (61% males, mean age 45) were included (65% axSpA, 25% PsA, 10% pSpA). Female gender [β= 0.14 (95% CI: 0.06, 0.23)], lower educational level [β = 0.35 (0.25, 0.45)) and single marital status [β = 0.09 (0.01, 0.17)] were associated with higher ASDAS. Living in lower GDP countries was also associated with higher ASDAS [β = 0.39 (0.16, 0.63)], and 7% of this association was mediated by b/tsDMARD uptake. Higher BASFI was similarly associated with female gender, lower education and living alone, without the effect of country-level SE factors. Female gender and lower educational level were associated with worse ASAS-HI, while more fatigue was associated with female gender and higher country-level SE factors [lower GDP, β = −0.46 (−0.89 to −0.04)]. No differences across disease phenotypes were found.

Conclusions

Our study shows country-driven variations in health outcomes in SpA, independently influenced by individual-level and country-level SE factors and without differences across disease phenotypes.
Morning stiffness precedes the development of rheumatoid arthritis and associates with systemic and subclinical joint inflammation in arthralgia patients
Authors: Krijbolder Doortje I , Wouters Fenne , van Mulligen Elise , van der Helm-van Mil Annette H M
Published: August 2021

Objectives

Morning stiffness (MS) is characteristic of RA and associates with markers of systemic and local inflammation in RA patients. In patients with arthralgia, MS is a cardinal symptom to recognize arthralgia at-risk for RA development [i.e. clinically suspect arthralgia (CSA)]. In CSA, MS is also assumed to reflect inflammation, but this has never been studied. Therefore we aimed to study whether MS in CSA patients is associated with systemic and subclinical joint inflammation.

Methods

A total of 575 patients presenting with CSA underwent laboratory investigations and contrast-enhanced 1.5 T MRI of the hand and forefoot (scored according to the Rheumatoid Arthritis MRI Score method). Associations of MS (duration ≥60 min) with the presence of subclinical joint inflammation (synovitis, tenosynovitis and osteitis) and increased CRP (≥5 mg/l) were determined with logistic regression. Additionally, the effect of MS duration (≥30, ≥60 and ≥120 min) was studied.

Results

A total of 195 (34%) CSA patients experienced MS. These patients more often had subclinical synovitis [34% vs 21%; odds ratio (OR) 1.95 (95% CI 1.32, 2.87)], subclinical tenosynovitis [36% vs 26%; OR 1.59 (95% CI 1.10, 2.31)] and increased CRP [31% vs 19%; OR 1.93 (95% CI 1.30, 2.88)] than patients without MS. In multivariable analyses, subclinical synovitis [OR 1.77 (95% CI 1.16, 2.69)] and CRP [OR 1.78 (95% CI 1.17–2.69)] remained independently associated with MS. In CSA patients who later developed RA, and thus in retrospect were ‘pre-RA’ at the time of CSA, MS was more strongly associated with subclinical synovitis [OR 2.56 (95% CI 1.04, 6.52)] and CRP [OR 3.86 (95% CI 1.45, 10.24)]. Furthermore, associations increased with longer MS durations.

Conclusion

Inflammation associates with MS in the CSA phase that preceded clinical arthritis. These results increase our understanding of MS when assessing arthralgia in clinical practice.
Accuracy in Near-Perfect Virus Phylogenies
Authors: Wertheim Joel O , Steel Mike , Sanderson Michael J
Published: August 2021

Phylogenetic trees from real-world data often include short edges with very few substitutions per site, which can lead to partially resolved trees and poor accuracy. Theory indicates that the number of sites needed to accurately reconstruct a fully resolved tree grows at a rate proportional to the inverse square of the length of the shortest edge. However, when inferred trees are partially resolved due to short edges, “accuracy” should be defined as the rate of discovering false splits (clades on a rooted tree) relative to the actual number found. Thus, accuracy can be high even if short edges are common. Specifically, in a “near-perfect” parameter space in which trees are large, the tree length $\xi$ (the sum of all edge lengths) is small, and rate variation is minimal, the expected false positive rate is less than $\xi/3$; the exact value depends on tree shape and sequence length. This expected false positive rate is far below the false negative rate for small $\xi$ and often well below 5% even when some assumptions are relaxed. We show this result analytically for maximum parsimony and explore its extension to maximum likelihood using theory and simulations. For hypothesis testing, we show that measures of split “support” that rely on bootstrap resampling consistently imply weaker support than that implied by the false positive rates in near-perfect trees. The near-perfect parameter space closely fits several empirical studies of human virus diversification during outbreaks and epidemics, including Ebolavirus, Zika virus, and SARS-CoV-2, reflecting low substitution rates relative to high transmission/sampling rates in these viruses.[Ebolavirus; epidemic; HIV; homoplasy; mumps virus; perfect phylogeny; SARS-CoV-2; virus; West Nile virus; Yule–Harding model; Zika virus.]
Israel: foreign trusts, trustee confidentiality and dispute resolution
Authors: Kaplan Alon , Eyal Lyat , Liberman Meytal
Published: August 2021

Trusts/foundations are a relatively new estate planning tool in Israel. As such, the Trust Law, passed in 1979, is basic legislation governing the principles of trust law. Together with the Tax Ordinance governing the taxation of trusts and court precedents, Israel trust practice is formed. Although, compared to extensive practices in other jurisdictions such as the UK or the USA, the trust practice in Israel is in its initial stages with much room to grow and expand. The factual basis and the necessity for establishing trusts lie in HNW families, social changes in the nuclear family and the need to care for the elderly and disabled. In addition, there is a growing practice of holding real estate via trust structures which remains to be resolved from a tax perspective as such structures are taxed under the Taxation of Real Property Law and not under the Tax Ordinance. This article will focus on several important legal issues involved in drafting and administering Israeli trusts/foundations; recognition of foreign trusts/foundations in Israel, the trustee's confidentiality obligation, and dispute resolution options for trusts.
Investigation of sag behaviour for aluminium conductor steel reinforced considering tensile stress distribution
Authors: Guo Deming , Wang Pengyu , Zheng Wencheng , Li Yang , Li Junwen , Tang Wenhu , Shi Liang , Liu Gang
Published: August 2021

Sag calculation plays an important role in overhead line design. Since the tensile stress of aluminium conductor steel reinforced (ACSR) is required for the sag calculation, an analysis on sag behaviour when considering the tensile stress distribution can be very useful to improve the accuracy of sag results. First, this paper analyses the ACSR tensile stress distribution arising from the temperature maldistribution through proposing a new calculation formula. A finite-element analysis (FEA) model of ACSR is conducted for the solution of the new formula. By using the results, the error and limitations of the existing sag calculation methods for ACSR are discussed. As the critical point of sag calculation, knee-point temperature is solved iteratively involving the tensile stress maldistribution phenomenon in aluminium wires. Based on this iterative solution, an improved analytical method for the ACSR sag calculation considering the creep effect is presented and also compared with the hybrid sag method. The results show that these two methods are basically coincident without the consideration of creep effect, while there are non-negligible differences between them as the creep strain is involved. Compared with the existing analytical methods, the improved sag calculation method proposed in this paper can be applied in more extensive situations.
Flying through gaps: how does a bird deal with the problem and what costs are there?
Authors: Henningsson Per
Published: August 2021

Animals flying in the wild often show remarkable abilities to negotiate obstacles and narrow openings in complex environments. Impressive as these abilities are, this must result in costs in terms of impaired flight performance. In this study, I used a budgerigar as a model for studying these costs. The bird was filmed in stereo when flying through a wide range of gap widths from well above wingspan down to a mere 1/4 of wingspan. Three-dimensional flight trajectories were acquired and speed, wingbeat frequency and accelerations/decelerations were calculated. The bird used two different wing postures to get through the gaps and could use very small safety margins (down to 6 mm on either side) but preferred to use larger when gap width allowed. When gaps were smaller than wingspan, flight speed was reduced with reducing gap width down to half for the smallest and wingbeat frequency was increased. I conclude that flying through gaps potentially comes with multiple types of cost to a bird of which the main may be: (i) reduced flight speed increases the flight duration and hence the energy consumption to get from point
A
to
B
, (ii) the underlying U-shaped speed to power relationship means further cost from reduced flight speed, and associated with it (iii) elevated wingbeat frequency includes a third direct cost.
Vibration analysis of irregular-shaped plates on simple supports
Authors: Ghosh Abhijit , DasGupta Anirvan
Published: August 2021

In this work, we propose a general perturbative approach for modal analysis of irregular-shaped plates of uniform thickness with uniform boundary conditions. Given a plate of irregular boundary, first, a uniform circular plate of identical thickness and area, centred at the centroid, is determined. The irregular boundary is then treated as a perturbation with a suitable smallness parameter, and is expressed as a generalized Fourier series. The frequency parameter, shape function and boundary conditions are then perturbed in terms of the smallness parameter. The homogeneous zeroth-order equation corresponds to the circular plate, which is exactly solvable. We show that the inhomogeneous equations in the higher orders can also be solved exactly using a particular solution structure. We can then construct the exact perturbative solution up to any order. The proposed method is demonstrated through the modal analysis of simply supported super-circular plates. The results are validated using the numerical results obtained from ANSYS
®
, which are an excellent match. Interestingly, the supposedly degenerate modes with an even number of nodal diameters of super-circular plates are found to split naturally.
Associations of white matter hyperintensities with networks of grey matter blood flow and volume in midlife adults: a CARDIA MRI substudy
Authors: Kim William S.H. , Luciw Nicholas J. , Atwi Sarah , Shirzadi Zahra , Dolui Sudipto , Detre John A. , Nasrallah Ilya M. , Swardfager Walter , Bryan R. Nick , Launer Lenore J. , MacIntosh Bradley J.
Published: August 2021

White matter hyperintensities (WMHs) are emblematic of cerebral small vessel disease, yet characterization at midlife is poorly studied. Here, we investigated whether WMH volume is associated with brain network alterations in midlife adults. 254 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study were selected and stratified by WMH burden yielding two groups of equal size (Lo- and Hi-WMH groups). We constructed group-level covariance networks based on cerebral blood flow (CBF) and grey matter volume (GMV) maps across 74 grey matter regions. Through consensus clustering, we found that both CBF and GMV covariance networks were partitioned into modules that were largely consistent between groups. Next, CBF and GMV covariance network topologies were compared between Lo- and Hi-WMH groups at global (clustering coefficient, characteristic path length, global efficiency) and regional (degree, betweenness centrality, local efficiency) levels. At the global level, there were no group differences in either CBF or GMV covariance networks. In contrast, we found group differences in the regional degree, betweenness centrality, and local efficiency of several brain regions in both CBF and GMV covariance networks. Overall, CBF and GMV covariance analyses provide evidence of WMH-related network alterations that were observed at midlife.
Aging-related olfactory loss is associated with olfactory stem cell transcriptional alterations in humans
Authors: Oliva Allison D. , Issa Khalil , Hachem Ralph Abi , Jang David , Gupta Rupali , Moseman E. Ashley , Matsunami Hiroaki , Goldstein Bradley J.
Published: August 2021

Presbyosmia, or aging related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) in the nasal fossa is the peripheral organ for olfaction, and is subject to acquired damage, suggesting a likely site of pathology in aging. OE basal stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis or repair. Accordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. Combining psychophysical testing with olfactory mucosa biopsy analysis, single cell RNA-sequencing (scRNA-seq), and human olfactory culture studies, we identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress, or the regulation of proliferation and differentiation. To facilitate further study of human OE stem cells, we developed an adult human basal cell culture model. Characterization of cultures using scRNA-seq confirmed maintenance of a reserve stem cell-like phenotype, and brief cytokine exposure in basal cell cultures resulted in increased expression of TP63, a transcription factor acting to prevent OE stem cell differentiation. Our data are consistent with a process by which aging-related inflammatory changes in OE stem cells may contribute to presbyosmia, via the disruption of normal epithelial homeostasis, suggesting that OE stem cells may represent a rational therapeutic target for restoration of olfaction.

One Sentence Summary

Single cell profiling suggests that inflammatory-associated olfactory epithelial stem cell dysfunction is associated with presbyosmia in humans.
Dose-dependent dissociation of pro-cognitive effects of donepezil on attention and cognitive flexibility in rhesus monkeys
Authors: Hassani Seyed A. , Lendor Sofia , Neumann Adam , Roy Kanchan Sinha , Boroujeni Kianoush Banaie , Hoffman Kari L. , Pawliszyn Janusz , Womelsdorf Thilo
Published: August 2021

BACKGROUND

Donepezil exerts pro-cognitive effects by non-selectively enhancing acetylcholine (ACh) across multiple brain systems. The brain systems that mediate pro-cognitive effects of attentional control and cognitive flexibility are the prefrontal cortex and the anterior striatum which have different pharmacokinetic sensitivities to ACh modulation. We speculated that these area-specific ACh profiles lead to distinct optimal dose-ranges for donepezil to enhance the cognitive domains of attention and flexible learning.

METHODS

To test for dose-specific effects of donepezil on different cognitive domains we devised a multi-task paradigm for nonhuman primates (NHPs) that assessed attention and cognitive flexibility. NHPs received either vehicle or variable doses of donepezil prior to task performance. We measured donepezil intracerebral and how strong it prevented the breakdown of ACh within prefrontal cortex and anterior striatum using solid-phase-microextraction neurochemistry.

RESULTS

The highest administered donepezil dose improved attention and made subjects more robust against distractor interference, but it did not improve flexible learning. In contrast, only a lower dose range of donepezil improved flexible learning and reduced perseveration, but without distractor-dependent attentional improvement. Neurochemical measurements confirmed a dose-dependent increase of extracellular donepezil and decreases in choline within the prefrontal cortex and the striatum.

CONCLUSIONS

The donepezil dose for maximally improving attention functions differed from the dose range that enhanced cognitive flexibility despite the availability of the drug in the major brain systems supporting these cognitive functions. Thus, the non-selective acetylcholine esterase inhibitor donepezil inherently trades improvement in the attention domain for improvement in the cognitive flexibility domain at a given dose range.
Natural reassortment of a segmented RNA arbovirus illustrates plasticity of phenotype in the arthropod vector and mammalian hostin vivo
Authors: Sanders Christopher , Veronesi Eva , Rajko-Nenow Paulina , Mertens Peter Paul Clement , Batten Carrie , Gubbins Simon , Darpel Karin , Carpenter Simon
Published: August 2021

Segmented RNA viruses are a taxonomically diverse group of 11 families that can infect plant, wildlife, livestock and human hosts. A shared feature of these viruses is the ability to exchange genome segments during co-infection of a host by a process termed ‘reassortment’. Reassortment enables rapid evolutionary change, but in the case of segmented RNA viruses utilising an arthropod vector is set against the constraint of purifying selection and genetic bottlenecks imposed by replication in two evolutionarily distant hosts. In this study, we use anin vivohost: arbovirus: vector model to investigate the impact of reassortment on two phenotypic traits: vector competence and virulence in the host. Bluetongue virus (BTV) (Reoviridae) is the causative agent of bluetongue (BT), an economically important disease of domestic and wild ruminants and deer. The genome of BTV is comprised of 10 linear segments of dsRNA and the virus is transmitted between ruminants byCulicoidesbiting midges (Diptera: Ceratopogonidae). Five strains of BTV representing three serotypes (BTV-1, BTV-4 and BTV-8) were isolated from naturally infected ruminants in Europe and parental/reassortant lineage status assigned through full genome sequencing. Each strain was then assessed in parallel for the ability to infectCulicoidesand to cause BT in sheep. Our results demonstrate that two reassortment strains, which themselves became established in the field, had obtained high replication ability inC. sonorensisfrom one of the parental virus strains which allowed inferences of the genome segments conferring this phenotypic trait.

IMPORTANCE

Reassortment between strains can lead to major shifts in the transmission parameters and virulence of segmented RNA viruses with consequences for spread, persistence and impact. The ability of these pathogens to change their phenotypes rapidly in response to selection pressure in new environments presents a major challenge in understanding factors driving emergence. Utilising a natural mammalian host-insect vector infection and transmission model, we demonstrated for the first time the genetic basis for a phenotypic trait of BTV within strains directly isolated from the field and, hence, selected and relevant for natural transmission.
Beyond Black vs White: Racial/Ethnic Disparities in Chronic Pain including Hispanic, Asian, Native American, and Multiracial U.S. Adults
Authors: Zajacova Anna , Grol-Prokopczyk Hanna , Fillingim Roger
Published: August 2021

Previous literature on race/ethnicity and pain has rarely included all major U.S. racial groups or examined the sensitivity of findings to different pain operationalizations. Using data from the 2010-2018 National Health Interview Surveys on adults 18+ (N=273,972), we calculate the weighted prevalence of six definitions of pain to provide a detailed description of chronic pain in White, Black, Hispanic, Asian, Native American, and multiracial groups. We also estimate logistic models to obtain relative disparities, including net of demographic and socioeconomic (SES) factors; finally, we calculate average predicted probabilities to show prevalence disparities in absolute terms. We find that Asian Americans have the lowest pain prevalence across all pain definitions or model specifications. In contrast, Native American and multiracial adults have the highest pain prevalence. This pain excess is due to the lower SES among Native Americans but remains significant and unexplained among multiracial adults. Whites, Blacks, and Hispanics fall in between. In this trio, Hispanics have the lowest prevalence, an advantage not attributable to immigrant status or SES. While most prior research focused on Black-White comparisons, these two groups differ relatively little. Blacks report lower prevalence of less severe pain definitions than Whites, but higher prevalence of severe pain. Net of SES, however, Blacks have significantly lower pain across all definitions. Overall, racial disparities are larger than previously recognized once all major racial groups are included, and these disparities are largely consistent across different operationalizations of pain.