bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics, management and changing incidence of children with empyema in a paediatric intensive care unit
Authors: Subhi Rami , Gelbart Ben , Ching Natasha , Thompson Jenny , Osowicki Joshua , Rozen Thomas H , Shanthikumar Shivanthan , Teague Warwick , Duke Trevor
Published: February 2022

Aim

Paediatric intensive care unit (PICU) admissions for empyema increased following the 13‐valent pneumococcal conjugate vaccine (PCV13). We describe the clinical characteristics, management and outcomes for children with empyema and compare incidence before and after PCV13.

Methods

Retrospective study of patients <18 years admitted to The Royal Children's Hospital Melbourne PICU with empyema between January 2016 and July 2019. We investigated the incidence of empyema during two time periods: 2007–2010 (pre‐PCV13) and 2016–2019 (post‐PCV13).

Results

Seventy‐one children (1.9% of all PICU admissions) were admitted to PICU with empyema between 2016 and 2019. Sixty‐one (86%) had unilateral disease, 11 (16%) presented with shock and 44 (62%) were ventilated. Streptococcus pneumoniae and group A Streptococcus were the most commonly identified pathogens. Forty‐five (63%) were managed with video‐assisted thoracoscopic surgery (VATS).

There was a 31% reduction in empyema hospitalisations as a proportion of all hospitalisations (IRR 0.69, 95% CI 0.59–0.8), but a 2.8‐fold increase in empyema PICU admissions as a proportion of all PICU admissions (95% CI 2.2–3.5, P < 0.001). For the PICU cohort, this was accompanied by reduction in PIM2 probability of death (median 1% vs. 1.9%, P = 0.02) and duration of intubation (median 69 h vs. 126.5 h, P = 0.045).

Conclusions

In children with empyema in PICU 62% required ventilation, 16% had features of shock and 63% received VATS. Empyema admissions, as a proportion of all PICU admissions, increased in the era post‐PCV13 compared to pre‐PCV13 despite no increase in illness severity at admission.
Related and unrelated product diversification and collaboration strategies: Comparison between the pharmaceutical and biopharmaceutical industries
Authors: Kim Keungoui , Lee Junmin , Hwang Junseok , Kim Eungdo
Published: February 2022

In pharmaceutical and biopharmaceutical industries, developing and commercializing products require great investments and intensive clinical trials. With regard to managing the risk and uncertainty of such product development, especially given the low success rates, product diversification and collaboration strategies can be instrumental for firms. Especially, the differences in product development complexity and market condition among industries require more case‐specific implications due to the absence of a universally applicable strategy, even in these two similar industries. To date, little is known or discussed regarding whether product diversification and collaboration strategies work differently by industry and to what extent their impact differs across industries. Accordingly, this study examines the impact of product diversification on firm performance and compares the diversification effects between the pharmaceutical and biopharmaceutical industries. Related product diversification (RPD), which involves diversifying existing product functions, and unrelated product diversification (UPD), which involves diversifying the selling market, are considered here, and their linear and curvilinear effects are examined for each industry. Furthermore, the mediating role of product diversification in the relationship between collaboration and performance is examined to explore diversification through collaboration and the effect of collaboration on firm performance. For empirical analysis, an integrated firm‐level dataset combining a full set of commercialized product information, collaboration, and statistics from Medtrack and Compustat are used. The results indicate that RPD enhances pharmaceutical firms' performance, while RPD and UPD contribute to biopharmaceutical firms' performance. In both cases, mediating effect of product diversification is found; however, collaboration is found to play different roles, thereby showing that collaboration enhances product diversification for pharmaceutical firms, while for biopharmaceutical firms it negatively affects product diversification, but positively affects performance. This study contributes to the literature by providing empirical evidence on how diversification should be treated differently across industries by considering product development complexity and market maturity.
Dual adhesive unipolar polysaccharides synthesized by overlapping biosynthetic pathways in Agrobacterium tumefaciens
Authors: Onyeziri Maureen C. , Hardy Gail G. , Natarajan Ramya , Xu Jing , Reynolds Ian P. , Kim Jinwoo , Merritt Peter M. , Danhorn Thomas , Hibbing Michael E. , Weisberg Alexandra J. , Chang Jeff H. , Fuqua Clay
Published: February 2022

Agrobacterium tumefaciens is a member of the Alphaproteobacteria that pathogenises plants and associates with biotic and abiotic surfaces via a single cellular pole. A. tumefaciens produces the unipolar polysaccharide (UPP) at the site of surface contact. UPP production is normally surface‐contact inducible, but elevated levels of the second messenger cyclic diguanylate monophosphate (cdGMP) bypass this requirement. Multiple lines of evidence suggest that the UPP has a central polysaccharide component. Using an A. tumefaciens derivative with elevated cdGMP and mutationally disabled for other dispensable polysaccharides, a series of related genetic screens have identified a large number of genes involved in UPP biosynthesis, most of which are Wzx‐Wzy‐type polysaccharide biosynthetic components. Extensive analyses of UPP production in these mutants have revealed that the UPP is composed of two genetically, chemically, and spatially discrete forms of polysaccharide, and that each requires a specific Wzy‐type polymerase. Other important biosynthetic, processing, and regulatory functions for UPP production are also revealed, some of which are common to both polysaccharides, and a subset of which are specific to each type. Many of the UPP genes identified are conserved among diverse rhizobia, whereas others are more lineage specific.
The molecular characteristics of low‐grade and high‐grade areas in desmoplastic infantile astrocytoma/ganglioglioma
Authors: Chiang Jason , Li Xiaoyu , Jin Hongjian , Wu Gang , Lin Tong , Ellison David W.
Published: February 2022

Aims

Desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIGs) are rare brain tumours of infancy. A distinctive feature of their histopathology is a combination of low‐grade and high‐grade features. Most DIA/DIGs can be surgically resected and have a good prognosis. However, high‐grade features often dominate recurrent tumours, some of which have a poor outcome. In this study, we test the hypothesis that low‐grade and high‐grade areas in DIA/DIGs have distinct molecular characteristics.

Methods

Tissue samples from microdissected low‐grade and high‐grade areas in 12 DIA/DIGs were analysed by DNA methylation profiling, whole exome sequencing, RNA sequencing and immunohistochemistry to search for potential differences at multiple molecular levels.

Results

Copy number variants among tumours and between the two morphologically distinct areas were infrequent. No recurrent genetic alterations were identified across the tumour series, and high‐grade areas did not have additional genetic alterations to explain their distinct morphology or biological behaviour. However, high‐grade areas showed relative hypomethylation in genes downstream of the transcription factors SOX9 and LEF1 and evidence of a core SOX9 transcription network alongside activation of the BMP, WNT and MAPK signalling pathways.

Conclusions

This study contributes to our knowledge of molecular genetic alterations in DIA/DIGs, uncovers molecular differences between the two distinct cell populations in these tumours and suggests potential therapeutic targets among the more proliferative cell population in DIA/DIGs.
Identification and critical appraisal of evidence for interventions for refractive error to support the development of the WHO package of eye care interventions: a systematic review of clinical practice guidelines
Authors: Evans Jennifer R , Lawrenson John G , Ramke Jacqueline , Virgili Gianni , Gordon Iris , Lingham Gareth , Yasmin Sumrana , Keel Stuart
Published: February 2022

Purpose

The World Health Organization is developing a Package of Eye Care Interventions (PECI) to support the integration of eye health care into national health programmes. Interventions included in the PECI should be based on robust evidence where available. Refractive error is a leading cause of blindness and vision impairment and is a PECI priority condition. The aim of this study was to provide high‐quality evidence to support the development of the PECI by identifying and critically appraising clinical practice guidelines (CPGs), and extracting recommendations for refractive error interventions.

Methods

We searched for CPGs on refractive error published in the last 10 years. We conducted the searches initially in February and March 2019 and repeated them in March 2020. We evaluated the quality of potentially relevant guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool.

Results

We identified 12 high‐quality CPGs relevant to refractive error, written by six organisations from three high‐income countries. Organisations used a variety of frameworks to assess the strength of recommendations based on available evidence, with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) being most common. Vision screening for children aged 3 to 5 years was recommended consistently. Evidence for screening and eye evaluations at other ages was weaker, although ophthalmic professional organisations consistently recommended regular evaluations. Recommendations on optical and laser correction of refractive error were limited and did not consider implications for low resource settings. Interventions for slowing myopia progression in children were recommended, but these will need regular updating as new evidence emerges.

Conclusions

Current high‐quality guidelines on refractive error have been formulated in high‐income countries. Recommendations focused on prevention and treatment of refractive error in low‐and middle‐income countries are lacking. Regular updating of systematic reviews and CPGs is essential to ensure that robust evidence is promptly appraised and incorporated into recommendations for eye health care practitioners.
Effects of milfoil weevils and weather on the control of Eurasian watermilfoil
Authors: Van Dyke Fred , Harju Seth , Korstad John , Goelzer Nathan , Wolfe Colten L. , Keas Brian
Published: February 2022

We examined the response of Eurasian watermilfoil (Myriophyllum spicatum) coverage on Manistee Lake, Michigan (U.S.A.) in the presence of milfoil weevils (Euhrychiopsis lecontei). Among 150 sites, milfoil presence declined from 2008 levels of 34 (23%) sites to 2 (1%) sites by 2015 coincident with cumulative stocking of 259,500 weevils from 2007 to 2014. Severe winter temperatures also were associated with milfoil declines. Each 1°C decline in average low temperature during the preceding winter was associated with 3.4 (95% CI 0.8–6.1) fewer sites with milfoil. Impacts of weevil herbivory on watermilfoil may be accentuated by severe winter temperatures. Lake managers should, when possible, integrate weather conditions with weevil stocking regimes to control Eurasian watermilfoil.
Urban poverty, growth, and inequality: A needed paradigm shift?
Authors: Wilson Edgar J. , Jayanthakumaran Kankesu , Verma Reetu
Published: February 2022

This paper calculates poverty and inequality elasticities using the latest‐available World Bank primary survey household consumption expenditure data for the rapidly growing urban sectors of India, Indonesia, and China. Our approach compares the conventional use of the overly simple headcount measure to the poverty gap squared (PG2) measures of poverty and focuses the effectiveness of reducing inequality on the disutility of the poor using a microeconomic utility‐based point elasticity measure of poverty loss. The calculations show that reducing urban inequality is more effective in reducing (1) urban poverty than promoting growth and (2) poverty distress more than that in the rural sector. The optimal policy prescription is to reduce urban inequality by targeting the urban very poor using thePG2measure. Further research is required to identify and quantify the determinants of the point elasticity magnitudes and the possible directions of causation.
Gaussian Differential Privacy
Authors: Dong Jinshuo , Roth Aaron , Su Weijie J.
Published: February 2022

In the past decade, differential privacy has seen remarkable success as a rigorous and practical formalization of data privacy. This privacy definition and its divergence based relaxations, however, have several acknowledged weaknesses, either in handling composition of private algorithms or in analysing important primitives like privacy amplification by subsampling. Inspired by the hypothesis testing formulation of privacy, this paper proposes a new relaxation of differential privacy, which we term ‘f-differential privacy’ (f-DP). This notion of privacy has a number of appealing properties and, in particular, avoids difficulties associated with divergence based relaxations. First, f-DP faithfully preserves the hypothesis testing interpretation of differential privacy, thereby making the privacy guarantees easily interpretable. In addition, f-DP allows for lossless reasoning about composition in an algebraic fashion. Moreover, we provide a powerful technique to import existing results proven for the original differential privacy definition to f-DP and, as an application of this technique, obtain a simple and easy-to-interpret theorem of privacy amplification by subsampling for f-DP. In addition to the above findings, we introduce a canonical single-parameter family of privacy notions within the f-DP class that is referred to as ‘Gaussian differential privacy’ (GDP), defined based on hypothesis testing of two shifted Gaussian distributions. GDP is the focal privacy definition among the family of f-DP guarantees due to a central limit theorem for differential privacy that we prove. More precisely, the privacy guarantees of any hypothesis testing based definition of privacy (including the original differential privacy definition) converges to GDP in the limit under composition. We also prove a Berry–Esseen style version of the central limit theorem, which gives a computationally inexpensive tool for tractably analysing the exact composition of private algorithms. Taken together, this collection of attractive properties render f-DP a mathematically coherent, analytically tractable and versatile framework for private data analysis. Finally, we demonstrate the use of the tools we develop by giving an improved analysis of the privacy guarantees of noisy stochastic gradient descent.
From the American South to South America: Testing whether patterns of competition in two‐round elections travel from the United States to Latin America
Authors: Bullock Charles S. , Singh Shane P.
Published: February 2022

Objective

In this paper, we seek to update and expand the understanding of whether the patterns of competition in two‐round elections in the United States exist in other countries.

Methods

Using insights from the well‐developed literature on two‐round elections in the U.S. South, we analyze an original data set covering two‐round presidential systems in Latin America. We focus on the likelihood that elections will go to a second round, and, once a second round happens, the role that first‐round electoral strength and incumbency status play in determining the ultimate outcome.

Results

Unlike previous work, our statistical model accounts for unobservable factors that simultaneously affect the likelihood of a second round occurring and of the first‐round leader winning that round.

Conclusions

Patterns of competition across U.S. and Latin American two‐round elections are similar, though incumbency status may be a bigger asset in the latter than in the former.
An assessment of potential pesticide transmission, considering the combined impact of soil texture and pesticide properties: A meta‐analysis
Authors: McGinley John , Harmon O’Driscoll Jenny , Healy Mark G. , Ryan Paraic C. , Mellander Per Eric , Morrison Liam , Callery Oisin , Siggins Alma
Published: February 2022

Pesticides are widely employed as a cost‐effective means of reducing the impacts of undesirable plants and animals. The aim of this paper is to develop a risk ranking of transmission of key pesticides through soil to waterways, taking into account physico‐chemical properties of the pesticides (soil half‐life and water solubility), soil permeability, and the relationship between adsorption of pesticides and soil texture. This may be used as a screening tool for land managers, as it allows assessment of the potential transmission risks associated with the use of specified pesticides across a spectrum of soil textures. The twenty‐eight pesticides examined were differentiated into three groups: herbicides, fungicides and insecticides. The highest risk of pesticide transmission through soils to waterways is associated with soils containing <20% clay or >45% sand. In a small number of cases, the resulting transmission risk is not influenced by soil texture alone. For example, for Phenmedipham, the transmission risk is higher for clay soils than for silt loam. The data generated in this paper may also be used in the identification of critical area sources, which have a high likelihood of pesticide transmission to waterways. Furthermore, they have the potential to be applied to GIS mapping, where the potential transmission risk values of the pesticides can be layered directly onto various soil textures.
Full genomic sequence of the HLA‐C*07:308 allele identified by next generation sequencing
Authors: Liacini Abdelhamid , Peters Lindsey , Gravante Christopher , Mancini Shannon , Geier Steven
Published: February 2022

Full‐length sequence of HLA‐C*07:308 covers the 5′‐untranslated region (UTR), all introns and exons and the 3′ UTR.
Placebo and nocebo effects in transfusion medicine
Authors: Badami Krishna G. , Chai Kern
Published: February 2022

Background

Our own observations suggested that placebo and nocebo effects may occur with transfusions. However these effects seem to have been poorly studied.

Objectives

To examine published information on, and draw attention to the possibility of, placebo and nocebo effects with transfusion.

Methods

Focused literature review.

Results

There is some information on placebo effects with clotting factors and this effect appears modest at best. There is very little published information on this regarding other fresh blood components. Although unknown biologic effects cannot be ruled out, there are hints that placebo effects might operate ‐ especially with red blood cell transfusions. There is practically no information on nocebo effects with transfusions.

Conclusions

There are ways of surmounting the practical and ethical difficulties involved, and obtaining better information on both types of effects. Individualised, contextualised, informed consenting of transfusion recipients may help to enhance placebo, and reduce nocebo, effects. This may be supportable ethically, and desirable clinically, and financially.
Ex vivo comparison of different thoracoabdominal stapler sizes for typhlectomy in canine cadavers
Authors: Matz Brad M. , Hlusko Katelyn C. , Linden Daniel S. , Tillson D. Michael , Hofmeister Erik
Published: February 2022

Objective

To determine the influence of staple size on leakage pressure of typhlectomy sites in canine cadavers.

Study design

Randomized, experimental cadaveric study.

Animals

Twenty‐four fresh canine cadavers.

Methods

Ileocecocolic segments were exteriorized following right paracostal laparotomy after euthanasia. Cecal base length and wall thickness were measured. Each cecum was randomly assigned to 1 of 3 groups (TA 30 V3 2.5 mm, TA 60 3.5 mm, and TA 60 4.8 mm). The cecal base was stapled and the cecum was removed. A 10 cm segment including the stapled cecal excision site was tested for initial leak pressure.

Results

The mean ± standard deviation body weights across the groups were 18.7 ± 6.1 kg, 16.2 ± 7.5 kg, and 14.2 ± 5.5 kg for the TA 30 V3 2.5 mm, TA 60 3.5 mm, and TA 60 4.8 mm groups, respectively (P = .48). There were no differences for mean cecal base length or wall thickness. Mean initial leak pressure (ILP) across groups was 182 ± 111 mmHg (TA 30 V3 2.5 mm), 112 ± 57 mmHg (TA 60 3.5 mm), and 77 ± 60 mmHg (TA 60 4.8 mm) (P = .78).

Conclusion

Each stapler size that was evaluated resulted in a mean ILP in excess of typical intraluminal pressures under normal circumstances. There were no differences among groups.

Clinical significance

The results of this cadaveric study support the use of any of the stapler sizes evaluated in similarly sized dogs. A prospective study is needed to be able to correlate stapler size and clinical outcome.
To regenerate or not to regenerate: Vertebrate model organisms of regeneration‐competency and ‐incompetency
Authors: Aztekin Can , Storer Mekayla A.
Published: February 2022

Why only certain species can regenerate their appendages (e.g. tails and limbs) remains one of the biggest mysteries of nature. Unlike anuran tadpoles and salamanders, humans and other mammals cannot regenerate their limbs, but can only regrow lost digit tips under specific circumstances. Numerous hypotheses have been postulated to explain regeneration‐incompetency in mammals. By studying model organisms that show varying regenerative abilities, we now have more opportunities to uncover what contributes to regeneration‐incompetency and functionally test which perturbations restore appendage regrowth. Particularly, Xenopus laevis tail and limb, and mouse digit tip model systems exhibit naturally occurring variations in regenerative capacities. Here, we discuss major hypotheses that are suggested to contribute to regeneration‐incompetency, and how species with varying regenerative abilities reflect on these hypotheses.
OPTIMAL DESIGNS OF GRID-CONNECTED ENERGY EFFICIENT AND RESILIENT RESIDENTIAL COMMUNITIES
Authors: Krarti Moncef , Dafoe Sarah , Baker Kyri
Published: February 2022

As demand continues to grow throughout the United States, new communities have unique opportunities to take advantage of load-side and generation-side integrations with the goal of reducing energy use, improving the environment, and increasing resilience. Most currently reported literature investigates energy efficiency and reduction of building energy consumption or on-site generation and net zero energy goals without resiliency performance analysis. This study examines the impacts of residential building characteristics and energy sources (i.e. electricity and natural gas) on the capacity of the on-site PV generation required to achieve net-zero energy and resiliency goals for a community in Longmont, Colorado. Six community load designs are shown to impact system sizes and costs for on-site generation and resilience. Gas and electrified minimum cost designs reduce source energy from their baselines by 17% and 47% respectively. Gas minimum cost designs reduce initial and annualized energy costs by 487 and247 per year, whereas electrified minimum cost designs increase initial costs by 4, 991 and reduce annualized energy costs by1,266 per year. Resilience designs show that with various outage durations, the longer the outage design case, the larger the system, but the greater the probability of surviving outages throughout the year, with gas communities representing lower probabilities of survivability than electrified communities.
Flow-modulated deposition of sp2-boron nitride using diborane and ammonia on chemomechanically polished (0001) 4H-SiC substrates
Authors: Jean-Remy Philip M. , Cabral Matthew J. , Davis Robert F.
Published: February 2022

Nanocrystalline sp2-BN thin films have been grown on (0001) 4H-SiC substrates at 1030 °C via continuous flow and discontinuous flow-modulated chemical vapor deposition techniques using diborane (B2H6) and ammonia (NH3) as the B and N sources, respectively. The latter technique enabled observations of both the effect of hydrogen purge steps between precursor injections and the length of injection times for B2H6 on the stoichiometry and microstructure of the films. Stoichiometric BN was achieved in all films grown continuously within the N/B gas phase ratio range of 20–200; this was not observed for the discontinuously grown films unless both the B2H6 flow rate and the injection time were minimized. Cross-sectional transmission electron microscopy of films grown both continuously and discontinuously at N/B = 200 and using short B2H6 injection times relative to that of NH3 for the latter process route revealed the initial growth of ∼4 nm thick partially ordered sp2-BN layers. A transition zone then formed containing randomly oriented polycrystalline grains. Excess B incorporated into the discontinuously grown films during long B2H6 injection times resulted in single layer mixtures of amorphous and sp2-BN without any observed ordering.
Reconstruction changes drive surface diffusion and determine the flatness of oxide surfaces
Authors: Franceschi Giada , Schmid Michael , Diebold Ulrike , Riva Michele
Published: February 2022

Surface diffusion on metal oxides is key in many areas of materials technology, yet it has been scarcely explored at the atomic scale. This work provides phenomenological insights from scanning tunneling microscopy on the link between surface diffusion, surface atomic structure, and oxygen chemical potential based on three model oxide surfaces: Fe2O3(11¯02), La1−xSrxMnO3(110), and In2O3(111). In all instances, changing the oxygen chemical potential used for annealing stabilizes reconstructions of different compositions while promoting the flattening of the surface morphology—a sign of enhanced surface diffusion. It is argued that thermodynamics, rather than kinetics, rules surface diffusion under these conditions: the composition change of the surface reconstructions formed at differently oxidizing conditions drives mass transport across the surface.
Forward masking of spectrotemporal modulation detection
Authors: Conroy Christopher , Byrne Andrew J. , Kidd Gerald
Published: February 2022

Recent work has suggested that there may be specialized mechanisms in the auditory system for coding spectrotemporal modulations (STMs), tuned to different combinations of spectral modulation frequency, temporal modulation frequency, and STM sweep direction. The current study sought evidence of such mechanisms using a psychophysical forward masking paradigm. The detectability of a target comprising upward sweeping STMs was measured following the presentation of modulated maskers applied to the same carrier. Four maskers were tested, which had either (1) the same spectral modulation frequency as the target but a flat temporal envelope, (2) the same temporal modulation frequency as the target but a flat spectral envelope, (3) the same spectral and temporal modulation frequencies as the target but the opposite sweep direction (downward sweeping STMs), or (4) the same spectral and temporal modulation frequencies as the target and the same sweep direction (upward sweeping STMs). Forward masking was greatest for the masker fully matched to the target (4), intermediate for the masker with the opposite sweep direction (3), and negligible for the other two (1, 2). These findings are consistent with the suggestion that the detectability of the target was mediated by an STM-specific coding mechanism with sweep-direction selectivity.
A spatial and temporal characterisation of single proton acoustic waves in proton beam cancer therapy
Authors: Deurvorst F. R. , Collado Lara G. , Matalliotakis A. , Vos H. J. , de Jong N. , Daeichin V. , Verweij M. D.
Published: February 2022

An in vivo range verification technology for proton beam cancer therapy, preferably in real-time and with submillimeter resolution, is desired to reduce the present uncertainty in dose localization. Acoustical imaging technologies exploiting possible local interactions between protons and microbubbles or nanodroplets might be an interesting option. Unfortunately, a theoretical model capable of characterising the acoustical field generated by an individual proton on nanometer and micrometer scales is still missing. In this work, such a model is presented. The proton acoustic field is generated by the adiabatic expansion of a region that is locally heated by a passing proton. To model the proton heat deposition, secondary electron production due to protons has been quantified using a semi-empirical model based on Rutherford's scattering theory, which reproduces experimentally obtained electronic stopping power values for protons in water within 10% over the full energy range. The electrons transfer energy into heat via electron-phonon coupling to atoms along the proton track. The resulting temperature increase is calculated using an inelastic thermal spike model. Heat deposition can be regarded as instantaneous, thus, stress confinement is ensured and acoustical initial conditions are set. The resulting thermoacoustic field in the nanometer and micrometer range from the single proton track is computed by solving the thermoacoustic wave equation using k-space Green's functions, yielding the characteristic amplitudes and frequencies present in the acoustic signal generated by a single proton in an aqueous medium. Wavefield expansion and asymptotic approximations are used to extend the spatial and temporal ranges of the proton acoustic field.
Distinct PEAK3 interactors and outputs expand the signaling potential of the PEAK pseudokinase family
Authors: Hou Jianmei , Nguyen Elizabeth V. , Surudoi Minglyanna , Roy Michael J. , Patel Onisha , Lucet Isabelle S. , Ma Xiuquan , Daly Roger J.
Published: February 2022

The pseudokinase scaffolds PEAK1 and PEAK2 are implicated in cancer cell migration and metastasis. We characterized the regulation and role of the third family member PEAK3 in cell signaling. Similar to PEAK1 and PEAK2, PEAK3 formed both homotypic and heterotypic complexes. In addition, like PEAK1, it bound to the adaptors Grb2 and CrkII. However, unlike PEAK1 and PEAK2, homodimerized PEAK3 also interacted with the ARF GTPase-activating protein ASAP1, the E3 ubiquitin ligase Cbl, and the kinase PYK2. Dimerization and subsequent phosphorylation on Tyr
24
, likely by a Src family kinase, were required for the binding of PEAK3 to Grb2 and ASAP1. Interactions with Grb2, CrkII, ASAP1, Cbl, and PYK2 exhibited contrasting dynamics upon cell stimulation with epidermal growth factor (EGF), in part due to PEAK3 dephosphorylation mediated by the phosphatase PTPN12. Overexpressing PEAK3 in mesenchymal-like MDA-MB-231 breast cancer cells enhanced cell elongation in a manner dependent on PEAK3 dimerization, and manipulation of PEAK3 expression demonstrated a positive role for this scaffold in regulating cell migration. Overexpressing PEAK3 in PEAK1/2 double-knockout MCF-10A breast epithelial cells enhanced acinar growth, impaired basement membrane integrity, and promoted invasion in three-dimensional cultures, with the latter two effects dependent on the binding of PEAK3 to Grb2 and ASAP1. PEAK1 and PEAK2 quantitatively and temporally influenced PEAK3 function. These findings characterize PEAK3 as an integral, signal-diversifying member of the PEAK family with scaffolding roles that promote cell proliferation, migration, and invasion.
Increased Dietary Manganese Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at Combating Staphylococcus aureus
Authors: Monteith Andrew J. , Miller Jeanette M. , Beavers William N. , Juttukonda Lillian J. , Skaar Eric P.
Published: February 2022

Dietary metals can modify the risk to infection. Previously, we demonstrated that heightened dietary manganese (Mn) during systemicStaphylococcus aureusinfection increasesS. aureusvirulence.
Evolution of the Quorum Sensing Regulon in Cooperating Populations of Pseudomonas aeruginosa
Authors: Smalley Nicole E. , Schaefer Amy L. , Asfahl Kyle L. , Perez Crystal , Greenberg E. Peter , Dandekar Ajai A.
Published: February 2022

Pseudomonas aeruginosa
uses quorum sensing (QS) to activate expression of dozens of genes (the QS regulon). Because there is strain-to-strain variation in the size and content of the QS regulon, we asked how the regulon might evolve during long-term
P. aeruginosa
growth when cells require some but not all the functions activated by QS.
High myopia as risk factor for the 10-year incidence of open-angle glaucoma in the Beijing Eye Study
Authors: Wang Ya Xing , Yang Hua , Wei Chuan Chuan , Xu Liang , Wei Wen Bin , Jonas Jost B
Published: February 2022

Purpose

To assess the 10-year incidence of open-angle glaucoma (OAG) and its associations in an adult Chinese population.

Methods

Longitudinal observational population-based study. Out of 4439 participants aged 40+ years participating in the Beijing Eye Study in 2001, 2695 individuals (60.7%) were re-examined in 2011, while 397 participants had died (8.5%).

Results

Incident OAG was found in 75 participants among 2494 individuals free of glaucoma at baseline. The 10-year OAG incidence (mean: 3.0%; 95% CI 2.5 to 3.5) increased from 1.8% (95% CI 1.3 to 2.4) in individuals aged 40–49 years, to 5.9% (95% CI 3.1 to 9.6) in participants aged 70+ years. OAG incidence was highest in the high myopia group (13.3%±6.3%, OR: 7.3; 95% CI 3.3 to 16.3), followed by the moderately myopic group (8.1%±4.3%, OR: 4.2; 95% CI 2.0 to 8.8) and the low myopic group (6.2%±2.8%, OR: 3.2; 95% CI 1.7 to 5.8), as compared with the emmetropic/hyperopic group (2.1%±0.8%). In multivariable analysis, higher OAG incidence was associated with older age (OR: 1.06; 95% CI 1.03 to 1.09), longer axial length (OR: 1.72; 95% CI 1.45 to 2.05), higher intraocular pressure (IOP) in 2001 (OR: 1.18; 95% CI 1.08 to 1.29), higher vertical cup/disc ratio (VCDR) (OR: 60.8; 95% CI 6.7 to 556) and thinner central corneal thickness (CCT) (OR: 0.98; 95% CI 0.97 to 0.99).

Conclusions

In a 10-year follow-up, high myopia was a major risk factor for the development of OAG with a 7.3-fold risk increase as compared with emmetropic eyes. Higher age, IOP, VCDR and thinner CCT were additionally related with an increased OAG incidence. The findings may be of importance to clinical protocols and screening strategies.
Exercise-induced laryngeal obstruction (EILO) in athletes: a narrative review by a subgroup of the IOC Consensus on ‘acute respiratory illness in the athlete’
Authors: Clemm Hege Havstad , Olin J Tod , McIntosh Cameron , Schwellnus Martin , Sewry Nicola , Hull James H , Halvorsen Thomas
Published: February 2022

Exercise-induced laryngeal obstruction (EILO) is caused by paradoxical inspiratory adduction of laryngeal structures during exercise. EILO is an important cause of upper airway dysfunction in young individuals and athletes, can impair exercise performance and mimic lower airway dysfunction, such as asthma and/or exercise-induced bronchoconstriction. Over the past two decades, there has been considerable progress in the recognition and assessment of EILO in sports medicine. EILO is a highly prevalent cause of unexplained dyspnoea and wheeze in athletes. The preferred diagnostic approach is continuous visualisation of the larynx (via laryngoscopy) during high-intensity exercise. Recent data suggest that EILO consists of different subtypes, possibly caused via different mechanisms. Several therapeutic interventions for EILO are now in widespread use, but to date, no randomised clinical trials have been performed to assess their efficacy or inform robust management strategies. The aim of this review is to provide a state-of-the-art overview of EILO and guidance for clinicians evaluating and treating suspected cases of EILO in athletes. Specifically, this review examines the pathophysiology of EILO, outlines a diagnostic approach and presents current therapeutic algorithms. The key unmet needs and future priorities for research in this area are also covered.
Non-alcoholic fatty liver disease (NAFLD): a significant predictor of gestational diabetes mellitus (GDM) and early pregnancy miscarriages—prospective study in Rajarata Pregnancy Cohort (RaPCo)
Authors: Koralegedara Iresha Sandamali , Warnasekara Janith Niwanthaka , Dayaratne Korale Gedara , De Silva Farika Nirmani , Premadasa Jagath Keerthi , Agampodi Suneth Buddhika
Published: February 2022

Background and aims

Non-alcoholic fatty liver disease (NAFLD) is increasing globally with a mounting body of evidence on various adverse effects on pregnancy. Yet, prospective studies, especially from low-income and middle-income countries, are lacking in examining the impact of NAFLD in pregnancy. In this study, we explored the effect of NAFLD on the development of gestational diabetes mellitus (GDM) and early pregnancy miscarriages.

Methods

A population-based prospective cohort study was conducted among first-trimester pregnant women who registered in the national pregnancy care programme during July–September 2019 in Anuradhapura district, Sri Lanka. Baseline clinical–biochemical parameters and ultrasound scan (USS) of the liver were done to assess fatty liver. Those who were normoglycaemic based on WHO criteria were followed up, and a repeat oral glucose tolerance test was performed between 24 and 28 weeks of gestation.

Results

Of the 632 pregnant women studied, 90 (14%) and 234 (37%) were diagnosed as having fatty liver grade (FLG) II and I, respectively. The cumulative incidence of GDM in FLG 0, I, and II were 11, 44, and 162 per 1000 pregnancies, respectively. After adjusting for age and other known risk factors, women with FLG II had a relative risk (RR) of 12.5 (95% CI 2.2 to 66.4) for developing GDM compared with FLG 0. In addition, women with FLG I (RR 2.1, 95% CI 1.01 to 4.64) and FLG II (RR 4.5, 95% CI 2.1 to 9.9) were significant risk factors for early pregnancy miscarriages, and FLG II remained as the only independent predictor of miscarriages after adjusting for age, parity, body mass index, blood sugar, blood pressure, and haemoglobin level (adjusted OR 4.2 (95% CI 1.9 to 9.1)).

Conclusion

In this rural south Asian community, NAFLD is shown to be a major risk factor for GDM and early pregnancy miscarriages. Therefore, routine identification of NAFLD through a simple USS may help in the early identification of high-risk mothers.
Why we need population data on gender norms, and why this is important for population health
Authors: King Tania , Perales Francisco , Sutherland Georgina
Published: February 2022

Gender norms are essential barometers of gender equality; inequitable gender norms are indicative of core inequalities in society that undermine the health of many groups. Fundamentally embedded in the gender system, prescriptive and restrictive gender norms have been shown to have deleterious effects on the health of women, men, girls and boys, as well as gender and sexual minorities. Gender norms are mutable, and there is potential to target and transform harmful and inequitable gender norms to drive gender equality. Gender-transformative approaches are needed, but a necessary first step is to identify and benchmark restrictive and inequitable gender norms, monitor change and progress, and highlight areas where interventions can be targeted for greatest effect. Efforts to do this are currently stymied by a lack of fit-for-purpose data. Routinely collected, population representative data on gender norms is urgently needed. This is vital to supporting and progressing gender equality and will contribute substantially to lifting population health.
Motor context modulates substantia nigra pars reticulata spike activity in patients with Parkinson’s disease
Authors: Tekriwal Anand , Felsen Gidon , Ojemann Steven G , Abosch Aviva , Thompson John A
Published: February 2022

Objective

The severity of motor symptoms in Parkinson’s disease (PD) depends on environmental conditions. For example, the presence of external patterns such as a rhythmic tone can attenuate bradykinetic impairments. However, the neural mechanisms for this context-dependent attenuation (e.g., paradoxical kinesis) remain unknown. Here, we investigate whether context-dependent symptom attenuation is reflected in single-unit activity recorded in the operating room from the substantia nigra pars reticulata (SNr) of patients with PD undergoing deep brain stimulation surgery. The SNr is known to influence motor planning and execution in animal models, but its role in humans remains understudied.

Methods

We recorded SNr activity while subjects performed cued directional movements in response to auditory stimuli under interleaved ‘patterned’ and ‘unpatterned’ contexts. SNr localisation was independently confirmed with expert intraoperative assessment as well as post hoc imaging-based reconstructions.

Results

As predicted, we found that motor performance was improved in the patterned context, reflected in increased reaction speed and accuracy compared with the unpatterned context. These behavioural differences were associated with enhanced responsiveness of SNr neurons—that is, larger changes in activity from baseline—in the patterned context. Unsupervised clustering analysis revealed two distinct subtypes of SNr neurons: one exhibited context-dependent enhanced responsiveness exclusively during movement preparation, whereas the other showed enhanced responsiveness during portions of the task associated with both motor and non-motor processes.

Conclusions

Our findings indicate the SNr participates in motor planning and execution, as well as warrants greater attention in the study of human sensorimotor integration and as a target for neuromodulatory therapies.
Varsity Medical Ethics Debate 2019: is authoritarian government the route to good health outcomes?
Authors: Zarif Azmaeen , Mittal Rhea , Popham Ben , Vorley Imogen C , Jindal Jessy , Morris Emily C
Published: February 2022

Authoritarian governments are characterised by political systems with concentrated and centralised power. Healthcare is a critical component of any state. Given the powers of an authoritarian regime, we consider the opportunities they possess to derive good health outcomes. The 2019 Varsity Medical Ethics Debate convened on the motion: ‘This house believes authoritarian government is the route to good health outcomes’ with Oxford as the Proposition and Cambridge as the Opposition. This article summarises and extends key arguments made during the 11th annual debate between medical students from the Universities of Oxford and Cambridge. By contrasting the principles underlying authoritarianism and democracy, it enables a discussion into how they translate into healthcare provision and the outcomes derived. Based on the foundation of said principles, an exploration of select cases represents examples of applications and the results. We analyse the past, present and future implications on the basis of fundamental patient-centred care.
How do prices of manufactured cigarettes and roll-your-own tobacco affect demand for these products? Tobacco price elasticity in Western Balkan countries
Authors: Vladisavljević Marko , Djukić Mihajlo , Jovanović Olivera , Zubović Jovan
Published: February 2022

Background and objective

Numerous studies have indicated that tobacco taxation is one of the most important policies to reduce tobacco consumption. However, its effectiveness crucially depends on consumer responses to price increases, that is, tobacco price elasticities. This paper analyses tobacco price elasticity in six Western Balkan countries.

Data and methods

We estimate own-price and cross-price elasticities of manufactured cigarettes (MCs) and roll-your-own (RYO) tobacco by using the methodological framework of the two-part model, regional variation in prices and 2019 Survey on Tobacco Consumption in Southeastern European countries (STC-SEE). STC-SEE provides a uniquely comparable nationally representative data on smoking behaviour for adult (18–85 years old) population for each country.

Results

Results suggest that higher prices of MCs are associated with lower prevalence of MC use, while higher prices of RYO are associated with lower intensity of RYO use. Furthermore, regions with higher MC prices have a higher likelihood of using RYO over MC, suggesting that RYO is used as a cheaper alternative to MC. Lastly, lower smoking prevalence and intensity are associated with more smoking restrictions and support for tobacco price increases.

Conclusion

Results suggest that, aiming to decrease smoking prevalence and intensity, governments should increase excises on all tobacco products. Since RYO is a cheaper alternative to MC, the increase of excises on RYO should be higher, so that after excise increase, the prices of the two products are approximately the same. To further reduce tobacco consumption, governments should combine increasing taxes on tobacco products with non-price measures, such as stricter smoking restrictions and smoke-free regulations.
Unified modeling of a tractor performance prototype based on ontology
Authors: Wu Yiwei , Zhou Zhili , Yan Xianghai
Published: February 2022

A tractor is a type of agricultural machinery with complex structure and harsh operating conditions. It is evolving toward a large-scale, multifunctional, and intelligent system. Digital prototype technology is an effective approach for experts in multidisciplinary fields to collaborate in the development of new tractor products. Tractor performance prototype design is an important part of realizing digital tractor design. In the modeling process, the performance prototype models designed by experts have a problem with inconsistent expressions, making tractor digital design difficult to implement. This study aims to investigate the unified modeling of a tractor performance prototype. The design process of the tractor performance prototype was analyzed according to the characteristics of new tractor product development. Combined with the ontology modeling method, the construction process of the tractor performance prototype ontology was designed. Based on ontology metamodel theory, a multidisciplinary unified modeling method for a tractor performance prototype is proposed, and an ontology metamodel architecture was constructed. Using a wheeled tractor as an example, a performance prototype ontology was designed. Subsequently, an ontology model was created and verified in Protégé. The results indicate that the model can be used for the digital design of new tractor product development. An ontology model database was established, which realized the sharing and management of ontology model data, and the effectiveness of the method was verified.
The Wu–Yau theorem on Sasakian manifolds
Authors: Chen Yong
Published: February 2022

In this paper, we proved that a compact Sasakian manifold [Formula: see text] with negative transverse holomorphic sectional curvature must have a Sasakian structure [Formula: see text] with negative transverse Ricci curvature. Similarly, a compact Sasakian manifold with nonpositive transverse holomorphic sectional curvature, then the negative first basic Chern class [Formula: see text] is transverse nef and we have the Miyaoka–Yau-type inequality. When transverse holomorphic sectional curvature is quasi-negative, we obtain a Chern number inequality.