bluuebunny/crossref_metadata_2025 huggingface dataset:
290 COMPARATIVE EFFICACY OF CORTICOSTEROIDS FORMULATIONS FOR THE MANAGEMENT OF EOSINOPHILIC OESOPHAGITIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.
Authors: Ma C , Feagan B , Claveau D , Landry L , Baribeau V , Beauchemin C
Published: September 2020

Topical corticosteroids are the foundation of pharmacologic treatment for eosinophilic oesophagitis (EoE) and administered mainly as nebulized swallowed fluticasone or budesonide viscous solution (BVS). Recently, a budesonide orodispersible tablet (BOT) has been approved for the treatment of EoE. The ideal formulation of topical corticosteroid delivery is unclear. Therefore, we aimed to compare the efficacy of BOT with other topical corticosteroid formulations for achieving histological remission in adult patients with EoE in a network meta-analysis (NMA).

Methods

A systematic literature review was performed using Medline and EMBASE from 1990 to July 2019. Eligible studies evaluated adult patients with a diagnosis of EoE treated with a topical corticosteroid in a randomized controlled trial. The outcome of interest was the proportion of patients achieving induction of histological remission (peak esophageal eosinophil count <5 eosinophils/high-power field). Direct comparisons were performed using the Mantel–Haenszel method and an NMA was performed using a fixed effect Bayesian framework with Markov Chain Monte Carlo simulations. Heterogeneity between studies was analyzed using the Cochrane Q test and consistency was verified.

Results

The search yielded 321 references and 6 (447 patients) were included in the quantitative summary. In the NMA, all formulations of topical corticosteroids were associated with greater histological remission rates than placebo. BOT was associated with a significantly higher rate of histological remission compared to BVS (odds ratio [OR] = 4.9; 95% credible interval [CrI] = 1.4,19.1), fluticasone (OR = 7.4; 95%CrI = 1.7,34.5), nebulized swallowed budesonide (NSB) (OR = 25.0; 95%CrI = 2.9,247.2) and placebo (OR = 387.6; 95%CrI = 97.5,2275.6). Similar trends were shown in direct comparisons. Analysis of the ranking of treatment options based on probability of effectiveness found BOT to be most probable followed by BVS, fluticasone, NSB, and placebo, consecutively.

Conclusion

This NMA of randomized controlled trials suggests that BOT is significantly more likely to achieve histological remission in adult patients with EoE compared to BVS, fluticasone, and NSB. We hypothesize that the superiority of BOT is related to increased contact time and targeting all inflammatory sites in the oesophagus, in contrast to other formulations. This NMA suggest that BOT is the first choice therapy amongst topical corticosteroids for the management of EoE.
324 INTRALUMINAL CONTINUOUS DECOMPRESSION USING A COMPUTER-CONTROLLED PORTABLE VACUUM PUMP FOR CONTROLLING CERVICAL ANASTOMOTIC LEAKAGE AFTER SUBTOTAL ESOPHAGECTOMY
Authors: Kaneko T , Shichinohe T , Uemura S , Narasaki H , Miyasaka D , Ebihara Y , Kurashima Y , Murakami S , Hirano S
Published: September 2020

Anastomotic leakage is one of the major complications that can occur after an esophagectomy. Usually, preemptive surgical intervention with prompt open drainage by cervical incision is the first choice. In our department, on the other hand, we perform intraluminal continuous decompression (ILCD) using a computer-controlled portable vacuum pump system (Thopaz®) as first-line therapy for leakage of the cervical anastomosis. In this study, we examine the effectiveness of this management.

Methods

Thirty-eight patients who underwent esophagectomy and cervical anastomosis and were diagnosed with leakage between May 2005 and October 2019, were studied. Until July 2014, cervical incision was generally performed, and ILCD or nasoesophageal extraluminal drainage (NEED) was added in some cases (conventional group). Since August 2014, we have performed ILCD and have added NEED in patients for whom ILCD was ineffective. A cervical incision was made for refractory cases (ILCD group). These two groups were analyzed statistically. Fifteen (39.5%) of the 38 patients were treated as the conventional group, and the remaining 23 (60.5%) were treated as the ILCD group.

Results

Thirteen patients in the conventional group (86.7%) required a cervical incision. Eight patients in the ILCD group (34.8%) underwent cervical incision and 9 (39.1%) underwent NEED. Drinking water orally was resumed at a median (range) of 35 (6–284) days from leakage in the conventional group and 18 (0–111) days from leakage in the ILCD group. The time to oral drinking was significantly shorter in the ILCD group (p = 0.0365). Six patients in the conventional group (40%) and one patient in the ILCD group (4.3%) had Clavien-Dindo IIIb or higher complications, indicating a significantly lower rate in the ILCD group (p = 0.0096).

Conclusion

The ILCD as first-line therapy is a minimally invasive treatment that effectively prevents exacerbation of leakage after subtotal esophagectomy.
Family Law Concentrate
Authors: Heenan Susan , Heenan Anna
Published: September 2020

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. Family Law Concentrate is supported by extensive online resources to take your learning further. It has been written by experts and covers all the key topics so that you can approach your exams with confidence. The clear, succinct coverage enables you to quickly grasp the fundamental principles of this area of law and helps you to succeed in exams. This guide has been rigorously reviewed and is endorsed by students and lecturers for level of coverage, accuracy, and exam advice. It is clear, concise, and easy to use, helping you get the most out of your revision. After an introduction, the book covers: families, civil partnerships, and cohabitation; nullity; divorce, dissolution, and judicial separation; domestic abuse; financial provision on divorce or dissolution; Children—private law; Children—public law; adoption; and child abduction. This, the fifth edition, has been fully updated in light of recent developments in the law, including the extension of civil partnerships to heterosexual couples, the Law Commission reviews of the law of surrogacy and marriage and proposals to reform the law of divorce and domestic abuse.
Equity & Trusts Concentrate
Authors: McDonald Iain , Street Anne
Published: September 2020

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. Equity & Trusts Concentrate covers all aspects of equity and trusts. Chapters look at the history and development of equity. The second chapter looks at the concept of a trust. The book also examines charitable, non-charitable purpose, secret, and implied trusts. Finally, issues relating to breach of trust and liabilities are covered. This edition has been updated to include: recent developments in the law and new case coverage.
English Legal System Concentrate
Authors: Thomas Mark , McGourlay Claire
Published: September 2020

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. English Legal Systems Concentrate starts with an introduction to the English legal system (ELS). It then looks at sources of law: domestic legislation, case law, and the effect of EU and international law. The text also examines the court structure. It then looks at personnel of the ELS. It moves on to consider the criminal justice system and the civil justice system. After that, it looks at funding access to the ELS. Finally, it looks to the future of the ELS.
A Granulocytic Signature Identifies COVID-19 and Its Severity
Authors: Vitte Joana , Diallo Aïssatou Bailo , Boumaza Asma , Lopez Alexandre , Michel Moïse , Allardet-Servent Jérôme , Mezouar Soraya , Sereme Youssouf , Busnel Jean-Marc , Miloud Tewfik , Malergue Fabrice , Morange Pierre-Emmanuel , Halfon Philippe , Olive Daniel , Leone Marc , Mege Jean-Louis
Published: September 2020

Background

An unbiased approach to SARS-CoV-2–induced immune dysregulation has not been undertaken so far. We aimed to identify previously unreported immune markers able to discriminate COVID-19 patients from healthy controls and to predict mild and severe disease.

Methods

An observational, prospective, multicentric study was conducted in patients with confirmed mild/moderate (n = 7) and severe (n = 19) COVID-19. Immunophenotyping of whole-blood leukocytes was performed in patients upon hospital ward or intensive care unit admission and in healthy controls (n = 25). Clinically relevant associations were identified through unsupervised analysis.

Results

Granulocytic (neutrophil, eosinophil, and basophil) markers were enriched during COVID-19 and discriminated between patients with mild and severe disease. Increased counts of CD15+CD16+ neutrophils, decreased granulocytic expression of integrin CD11b, and Th2-related CRTH2 downregulation in eosinophils and basophils established a COVID-19 signature. Severity was associated with emergence of PD-L1 checkpoint expression in basophils and eosinophils. This granulocytic signature was accompanied by monocyte and lymphocyte immunoparalysis. Correlation with validated clinical scores supported pathophysiological relevance.

Conclusions

Phenotypic markers of circulating granulocytes are strong discriminators between infected and uninfected individuals as well as between severity stages. COVID-19 alters the frequency and functional phenotypes of granulocyte subsets with emergence of CRTH2 as a disease biomarker.
Alzheimer Disease Pathogenesis: The Role of Autoimmunity
Authors: Lim Bryant , Prassas Ioannis , Diamandis Eleftherios P
Published: September 2020

Background

In addition to deposits of amyloid β (Aβ) plaques and neurofibrillary tangles, growing evidence demonstrates that complex and multifaceted biological processes can arise during Alzheimer disease (AD) pathogenesis. The recent failures of clinical trials based on the amyloid hypothesis and the presence of Aβ plaques in cognitively healthy elderly persons without AD point toward a need to explore novel pathobiological mechanisms of AD.

Content

In the search for alternative AD mechanisms, numerous genome-wide association studies and mechanistic discoveries suggest a potential immunologic component of the disease. However, new experimental tools are needed to uncover these immunogenic components. The current methods, such as ELISAs or protein microarrays, have limitations of low throughput and/or sensitivity and specificity. In this article, we briefly discuss evidence of potential autoimmune contributions to AD pathobiology, describe the current methods for identifying autoantibodies in patient fluids, and outline our own efforts to develop new techniques for novel autoantibody biomarker discovery.

Uncovering the putative autoimmune components of AD may be crucial in paving the way to new concepts for pathogenesis, diagnosis, and therapy.

Impact Statement

In addition to deposits of amyloid β plaques and neurofibrillary tangles, growing evidence demonstrates that complex and multifaceted biological processes can arise during Alzheimer disease (AD) pathogenesis. Numerous research directions, including genome-wide association, clinical correlation, and mechanistic studies, have pointed to a potential autoimmunologic contribution to AD pathology. We present research suggesting the association between autoimmunity and AD and demonstrate the need for new laboratory techniques to further characterize potential brain antigen-specific autoantibodies. Uncovering the putative autoimmune components of AD may be crucial in paving the way to new concepts for pathogenesis, diagnosis, and therapy.
Patient interest in and barriers to telemedicine video visits in a multilingual urban safety-net system
Authors: Khoong Elaine C , Butler Blythe A , Mesina Omar , Su George , DeFries Triveni B , Nijagal Malini , Lyles Courtney R
Published: September 2020

Objective

To determine interest in and barriers to video visits in safety-net patients with diverse age, racial/ethnic, or linguistic background.

Materials and Methods

We surveyed patients in an urban safety-net system to assess: interest in video visits; ability to successfully complete test video visits; and barriers to successful completion of test video visits.

Results

Among 202 participants, of which 177 (87.6%) were persons of color and 113 (55.9%) preferred non-English languages, 132 (65.3%) were interested in and 109 (54.0%) successfully completed a test video visit. Younger age, non-English preference, and prior smartphone application use were associated with interest. Over half (n = 112) reported barriers to video visits; Internet/data access was the most common barrier (n = 50, 24.8%).

Conclusion

Safety-net patients are interested in video visits and able to successfully complete test visits. Internet or mobile data access is a common barrier in even urban safety-net settings and may impact equitable telemedicine access.
Validation of the SafTest Percent Fat for the Measurement of the Fat Content of Meat Meals, Fish Meal, and Potato Chips, Crackers, and Other and Grain-Based Snack Products: AOAC Performance Tested MethodSM #082004
Authors: Gordon Virginia C , Rainey Christopher C , Studmire Willainia C
Published: September 2020

Background

The Official American Oil Chemists Society (AOCS) Standard Procedure Aa 4–38, AOCS Standard Procedure Am 5–04, ISO 11085:2015, and similar methods are based on extraction of fats from food products using organic solvents. These methods require large volumes of organic solvents and up to 18-hour extractions. The SafTest Percent Fat measures fat content as “total triglycerides” in solubilized snack products and meals using micro-analytical and membrane separation principles.

Objective

The study objective is to validate the SafTest Percent Fat in an internal study and an independent laboratory study.

Method

Comparability to AOCS Standard Procedure Aa 4–38 or AOCS Standard Procedure Am 5–04, LOQ, selectivity, robustness, stability, and consistency were determined.

Results

Mean recoveries from replicate analyses of SafTest control samples at three concentrations yielded 101 to 103%. The relative standard deviations of repeatability (RSDr) were below 5%. Studies of meat meals and snacks analyzed using the SafTest Percent Fat demonstrated RSDr of 2.3 to 5.6% compared to 2.6 to 4.9% for AOCS Aa 4–38. The method demonstrated average recoveries ranging from 88.8 to 116.2% compared to the AOCS methods results performed in two contract laboratory studies and an independent laboratory validation.

Conclusions

The SafTest Percent Fat test can determine fat content in meals and snack matrices with accuracy and precision comparable to results from AOCS Aa 4–38 and AOCS Am 5–04.

Highlights

The SafTest Percent Fat test uses small reagent volumes, instrumental analysis, easy-to-use standardized procedures, and rapid analysis times for fat content determination.
Practical implementation of high-resolution electron ptychography and comparison with off-axis electron holography
Authors: Blackburn Arthur M , McLeod Robert A
Published: September 2020

Ptychography is a coherent diffractive imaging technique that can determine how an electron wave is transmitted through an object by probing it in many small overlapping regions and processing the diffraction data obtained at each point. The resulting electron transmission model describes both phase and amplitude changes to the electron wave. Ptychography has been adopted in transmission electron microscopy in recent years following advances in high-speed direct electron detectors and computer algorithms which now make the technique suitable for practical applications. Its ability to retrieve quantitative phase information at high spatial resolution makes it a plausible alternative or complement to electron holography. Furthermore, unlike off-axis electron holography, it can provide phase information without an electron bi-prism assembly or the requirement of a minimally structured region adjacent to the region of interest in the object. However, it does require a well-calibrated scanning transmission electron microscope and a well-managed workflow to manage the calibration, data acquisition and reconstruction process to yield a practical technique. Here we detail this workflow and highlight how this is greatly assisted by acquisition management software. Through experimental data and modelling we also explore the similarities and differences between high-resolution ptychography and electron holography. Both techniques show a dependence of the recovered phase on the crystalline orientation of the material which is attributable to dynamical scattering. However, the exact nature of the variation differs reflecting fundamental expectations, but nonetheless equally useful information is obtained from electron holography and the ptychographically determined object transmission function.
Carrot hairy roots: factories for secondary metabolite production
Authors: Pedreño María A , Almagro Lorena
Published: September 2020

This article comments on:

Barba-Espín G, Chen S-T, Agnolet S, Hegelund JN, Stanstrup J, Christensen JH, Müller R, Lütken H. 2020. Ethephon-induced changes in antioxidants and phenolic compounds in anthocyanin-producing black carrot hairy root cultures. Journal of Experimental Botany 71, 7030–7045.
On the lineage of Aspergillus fumigatus isolates in common laboratory use
Authors: Bertuzzi Margherita , van Rhijn Norman , Krappmann Sven , Bowyer Paul , Bromley Michael J , Bignell Elaine M
Published: September 2020

The origin of isolates routinely used by the community of Aspergillus fumigatus researchers is periodically a matter of intense discussion at our centre, as the construction of recombinant isolates have sometimes followed convoluted routes, the documentation describing their lineages is fragmented, and the nomenclature is confusing. As an aide memoir, not least for our own benefit, we submit the following account and tabulated list of strains (Table 1) in an effort to collate all of the relevant information in a single, easily accessible document. To maximise the accuracy of this record we have consulted widely amongst the community of Medical Mycologists using these strains. All the strains described are currently available from one of these organisations, namely the Fungal Genetics Stock Centre (FGSC), FungiDB, Ensembl Fungi and The National Collection of Pathogenic Fungi (NCPF) at Public Health England. Display items from this manuscript are also featured on FungiDB.

Lay abstract

We present a concise overview on the definition, origin and unique genetic makeup of the Aspergillus fumigatus isolates routinely in use by the fungal research community, to aid researchers to describe past and new strains and the experimental differences observed more accurately.
The neutral hydrogen distribution in large-scale haloes from 21-cm intensity maps
Authors: Tramonte Denis , Ma Yin-Zhe
Published: September 2020

We detect the neutral hydrogen (H i) radial brightness temperature profile in large-scale haloes by stacking 48 430 galaxies selected from the 2dFGRS catalogue on to a set of 21-cm intensity maps obtained with the Parkes radio telescope, spanning a total area of ∼1300 deg2 on the sky and covering the redshift range 0.06 ≲ z ≲ 0.10. Maps are obtained by removing both 10 and 20 foreground modes in the principal component analysis. We perform the stack at the map level and extract the profile from a circularly symmetrized version of the halo emission. We detect the H i halo emission with the significance 12.5σ for the 10-mode and 13.5σ for the 20-mode removed maps at the profile peak. We jointly fit for the observed halo mass Mv and the normalization $c_{0,\rm H\, \small{I}}$ for the H i concentration parameter against the reconstructed profiles, using functional forms for the H i halo abundance proposed in the literature. We find $\log _{10}{(M_{\rm v}/\text{M}_{\odot })}= 16.1^{+0.1}_{-0.2}$, $c_{0,\rm H\, \small{I}}=3.5^{+0.7}_{-1.0}$ for the 10-mode and $\log _{10}{(M_{\rm v}/\text{M}_{\odot })}= 16.5^{+0.1}_{-0.2}$, $c_{0,\rm H\, \small{I}}=5.3^{+1.1}_{-1.7}$ for the 20-mode removed maps. These estimates show the detection of the integrated contribution from multiple galaxies located inside very massive haloes. We also consider subsamples of 13 979 central and 34 361 satellite 2dF galaxies separately, and obtain marginal differences suggesting satellite galaxies are H i-richer. This work shows for the first time the feasibility of testing theoretical models for the H i halo content directly on profiles extracted from 21-cm maps and opens future possibilities for exploiting upcoming H i intensity-mapping data.
How do central and satellite galaxies quench? – Insights from spatially resolved spectroscopy in the MaNGA survey
Authors: Bluck Asa F L , Maiolino Roberto , Piotrowska Joanna M , Trussler James , Ellison Sara L , Sánchez Sebastian F , Thorp Mallory D , Teimoorinia Hossen , Moreno Jorge , Conselice Christopher J
Published: September 2020

We investigate how star formation quenching proceeds within central and satellite galaxies using spatially resolved spectroscopy from the SDSS-IV MaNGA DR15. We adopt a complete sample of star formation rate surface densities (ΣSFR), derived in Bluck et al. (2020), to compute the distance at which each spaxel resides from the resolved star forming main sequence (ΣSFR − Σ* relation): ΔΣSFR. We study galaxy radial profiles in ΔΣSFR, and luminosity weighted stellar age (AgeL), split by a variety of intrinsic and environmental parameters. Via several statistical analyses, we establish that the quenching of central galaxies is governed by intrinsic parameters, with central velocity dispersion (σc) being the most important single parameter. High mass satellites quench in a very similar manner to centrals. Conversely, low mass satellite quenching is governed primarily by environmental parameters, with local galaxy overdensity (δ5) being the most important single parameter. Utilizing the empirical MBH − σc relation, we estimate that quenching via AGN feedback must occur at $M_{\rm BH} \ge 10^{6.5-7.5} \, \mathrm{M}_{\odot }$, and is marked by steeply rising ΔΣSFR radial profiles in the green valley, indicating ‘inside-out’ quenching. On the other hand, environmental quenching occurs at overdensities of 10–30 times the average galaxy density at z∼ 0.1, and is marked by steeply declining ΔΣSFR profiles, indicating ‘outside-in’ quenching. Finally, through an analysis of stellar metallicities, we conclude that both intrinsic and environmental quenching must incorporate significant starvation of gas supply.
How many components? Quantifying the complexity of the metallicity distribution in the Milky Way bulge with APOGEE
Authors: Rojas-Arriagada Alvaro , Zasowski Gail , Schultheis Mathias , Zoccali Manuela , Hasselquist Sten , Chiappini Cristina , Cohen Roger E , Cunha Katia , Fernández-Trincado José G , Fragkoudi Francesca , García-Hernández D A , Geisler Doug , Gran Felipe , Lian Jianhui , Majewski Steven , Minniti Dante , Monachesi Antonela , Nitschelm Christian , Queiroz Anna B A
Published: September 2020

We use data of ∼13 000 stars from the Sloan Digital Sky Survey/Apache Point Observatory Galactic Evolution Experiment survey to study the shape of the bulge metallicity distribution function (MDF) within the region |ℓ| ≤ 11° and |b| ≤ 13°, and spatially constrained to RGC ≤ 3.5 kpc. We apply Gaussian mixture modelling and non-negative matrix factorization decomposition techniques to identify the optimal number and the properties of MDF components. We find that the shape and spatial variations of the MDF (at [Fe/H] ≥ −1 dex) are well represented as a smoothly varying contribution of three overlapping components located at [Fe/H] = +0.32, −0.17, and −0.66 dex. The bimodal MDF found in previous studies is in agreement with our trimodal assessment once the limitations in sample size and individual measurement errors are taken into account. The shape of the MDF and its correlations with kinematics reveal different spatial distributions and kinematical structure for the three components co-existing in the bulge region. We confirm the consensus physical interpretation of metal-rich stars as associated with the secularly evolved disc into a boxy/peanut X-shape bar. On the other hand, metal-intermediate stars could be the product of in-situ formation at high redshift in a gas-rich environment characterized by violent and fast star formation. This interpretation would help us to link a present-day structure with those observed in formation in the centre of high-redshift galaxies. Finally, metal-poor stars may correspond to the metal-rich tail of the population sampled at lower metallicity from the study of RR Lyrae stars. Conversely, they could be associated with the metal-poor tail of the early thick disc.
OH maser towards IRAS 06056+2131: polarization parameters and evolution status
Authors: Darwish M S , Richards A M S , Etoka S , Edris K A , Saad S M , Beheary M M , Fuller G A
Published: September 2020

We present high-angular resolution observations of OH maser emission towards the high-mass star-forming region IRAS 06056+2131. The observations were carried out using the UK radio interferometer array, Multi-Element Radio Linked Interferometer Network (MERLIN) in the OH main lines at 1665 and 1667 MHz, in addition to the OH satellite line at 1720 MHz. The results of this study reveal the small upper limit to the size of emission in the 1665-MHz line with an estimated total intensity of ∼4 Jy. We did not detect any emission from the 1667 and 1720-MHz lines. The full polarization mode of MERLIN enables us to investigate the magnetic field in the OH maser region. In this transition, a Zeeman pair is identified from which a magnetic strength of ∼−1.5 mG is inferred. Our results show that IRAS 06056+2131 is highly polarized, with ∼ 96 ${{\ \rm per\ cent}}$ circular polarization and ∼6 ${{\ \rm per\ cent}}$ linear polarization. The linear polarization angle is ∼29°, implying a magnetic field which could be aligned with the outflow direction detected towards this region, but the actual magnetic field direction has an uncertainty of up to 110° due to the possible effects of Faraday rotation. The star-forming evolutionary status of the embedded protostellar object is discussed.
Stellar velocity dispersion and initial mass function gradients in dissipationless galaxy mergers
Authors: Nipoti Carlo , Cannarozzo Carlo , Calura Francesco , Sonnenfeld Alessandro , Treu Tommaso
Published: September 2020

The stellar initial mass function (IMF) is believed to be non-universal among early-type galaxies (ETGs). Parametrizing the IMF with the so-called IMF mismatch parameter αIMF, which is a measure of the stellar mass-to-light ratio of an ensemble of stars and thus of the ‘heaviness’ of its IMF, one finds that for ETGs αe (i.e. αIMF integrated within the effective radius Re) increases with σe (the line-of-sight velocity dispersion σlos integrated within Re) and that, within the same ETG, αIMF tends to decrease outwards. We study the effect of dissipationless (dry) mergers on the distribution of the IMF mismatch parameter αIMF in ETGs using the results of binary major and minor merging simulations. We find that dry mergers tend to make the αIMF profiles of ETGs shallower, but do not alter significantly the shape of the distributions in the spatially resolved σlos–αIMF space. Individual galaxies undergoing dry mergers tend to decrease their αe, due to erosion of αIMF gradients and mixing with stellar populations with lighter IMF. Their σe can either decrease or increase, depending on the merging orbital parameters and mass ratio, but tends to decrease for cosmologically motivated merging histories. The αe–σe relation can vary with redshift as a consequence of the evolution of individual ETGs: based on a simple dry-merging model, ETGs of given σe are expected to have higher αe at higher redshift, unless the accreted satellites are so diffuse that they contribute negligibly to the inner stellar distribution of the merger remnant.
Preclinical and first-in-human-brain-cancer applications of [18F]poly (ADP-ribose) polymerase inhibitor PET/MR
Authors: Young Robert J , Demétrio De Souza França Paula , Pirovano Giacomo , Piotrowski Anna F , Nicklin Philip J , Riedl Christopher C , Schwartz Jazmin , Bale Tejus A , Donabedian Patrick L , Kossatz Susanne , Burnazi Eva M , Roberts Sheryl , Lyashchenko Serge K , Miller Alexandra M , Moss Nelson S , Fiasconaro Megan , Zhang Zhigang , Mauguen Audrey , Reiner Thomas , Dunphy Mark P
Published: September 2020

Background

We report preclinical and first-in-human-brain-cancer data using a targeted poly (ADP-ribose) polymerase 1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment-related changes.

Methods

We applied a glioma model in p53-deficient nestin/tv-a mice, which were injected with [18F]PARPi and then sacrificed 1 h post-injection for brain examination. We also prospectively enrolled patients with brain cancers to undergo dynamic [18F]PARPi acquisition on a dedicated positron emission tomography/magnetic resonance (PET/MR) scanner. Lesion diagnosis was established by pathology when available or by Response Assessment in Neuro-Oncology (RANO) or RANO-BM response criteria. Resected tissue also underwent PARPi-FL staining and PARP1 immunohistochemistry.

Results

In a preclinical mouse model, we illustrated that [18F]PARPi crossed the blood–brain barrier and specifically bound to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment-related changes independent of blood–brain barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancerous than in noncancerous tissue. Specificity was also corroborated by blocking fluorescent tracer uptake with an excess unlabeled PARP inhibitor in patient cancer biospecimen.

Conclusions

Although larger studies are necessary to confirm and further explore this tracer, we describe the promising performance of [18F]PARPi as a diagnostic tool to evaluate patients with brain cancers and possible treatment-related changes.
COVID-19 mortality among Indigenous people in Brazil: a nationwide register-based study
Authors: Santos Victor Santana , Souza Araújo Adriano Antunes , de Oliveira Jarbas Ribeiro , Quintans-Júnior Lucindo José , Martins-Filho Paulo Ricardo
Published: September 2020

Coronavirus disease 2019 (COVID-19) has disproportionately affected Black people and minority ethnic groups, but there are limited data regarding the impact of disease on Indigenous people. Herein, we investigated the burden of COVID-19 on the Indigenous population in Brazil. We performed a populational-based study including all cases and deaths from COVID-19 among Brazilian Indigenous people from 26 February to 28 August 2020. Data were obtained from official Brazilian information systems. We calculated incidence, mortality and fatality rates for the Indigenous population for each of the five Brazilian regions. Brazil had an incidence and a mortality rate of 3546.4 cases and 65.0 deaths per 100 000 population, respectively. The case fatality rate (CFR) was 1.8%. The Central-West had the higher estimates of disease burden among Brazilian Indians (incidence rate: 3135.0/100 000; mortality rate: 101.2/100 000 and CFR: 3.2%) followed by the North region (incidence rate: 5664.4/100 000; mortality rate: 92.2/100 000 and CFR: 1.6%). Governmental actions should guarantee the isolation, monitoring and testing capabilities of Indigenous people and rapidly to provide social protection and health facilities.
Lord Burrows on Legislative Intention, Statutory Purpose, and the ‘Always Speaking’ Principle
Authors: Goldsworthy Jeffrey
Published: September 2020

In his 2017 Hamlyn Lectures, Professor (now Lord) Burrows set out his opinions about statutory interpretation. Given his recent appointment to the UK Supreme Court, these opinions now have more practical importance than those of most academic theorists. One of his main theses is that the modern approach to statutory interpretation, which focuses on text, context and purpose, should not include any reference to legislative intention. He dismisses this as ‘an unhelpful fiction or mask that should be avoided altogether’. I show that this thesis is mistaken, internally inconsistent, and might in practice undermine sound interpretation based on fundamental constitutional principles.
Perfluorooctanesulfonic Acid and Perfluorohexanesulfonic Acid Alter the Blood Lipidome and the Hepatic Proteome in a Murine Model of Diet-Induced Obesity
Authors: Pfohl Marisa , Ingram Lishann , Marques Emily , Auclair Adam , Barlock Benjamin , Jamwal Rohitash , Anderson Dwight , Cummings Brian S , Slitt Angela L
Published: September 2020

Perfluoroalkyl substances (PFAS) represent a family of environmental toxicants that have infiltrated the living world. This study explores diet-PFAS interactions and the impact of perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic (PFHxS) on the hepatic proteome and blood lipidomic profiles. Male C57BL/6J mice were fed with either a low-fat diet (10.5% kcal from fat) or a high fat (58% kcal from fat) high carbohydrate (42 g/l) diet with or without PFOS or PFHxS in feed (0.0003% wt/wt) for 29 weeks. Lipidomic, proteomic, and gene expression profiles were determined to explore lipid outcomes and hepatic mechanistic pathways. With administration of a high-fat high-carbohydrate diet, PFOS and PFHxS increased hepatic expression of targets involved in lipid metabolism and oxidative stress. In the blood, PFOS and PFHxS altered serum phosphatidylcholines, phosphatidylethanolamines, plasmogens, sphingomyelins, and triglycerides. Furthermore, oxidized lipid species were enriched in the blood lipidome of PFOS and PFHxS treated mice. These data support the hypothesis that PFOS and PFHxS increase the risk of metabolic and inflammatory disease induced by diet, possibly by inducing dysregulated lipid metabolism and oxidative stress.
Advantages of Maggot Debridement Therapy for Chronic Wounds: A Bibliographic Review
Authors: Moya-López José , Costela-Ruiz Victor , García-Recio Enrique , Sherman Ronald A. , De Luna-Bertos Elvira
Published: September 2020

Maggot debridement therapy (MDT) is effective for ulcer debridement, achieving it in less time than other therapies. It offers a benefit to healing. However, it is unclear whether maggots reduce treatment time and there is considerable controversy around the treatment's potential antimicrobial action and cost-effectiveness. Nevertheless, it can be effective in preventing amputations and reducing the need for systemic antibiotics. This bibliographic review assesses the advantages of MDT as a treatment for chronic wounds through the review of several larval properties. The review was carried out by consulting biomedical databases including CINAHL, MEDLINE (PubMed), and Scopus, and concludes that MDT is an effective debridement and potential technique to facilitate healing. However, more data is needed on the wound type application frequency and the efficacy of treatment.

GENERAL PURPOSE

To present an overview of the advantages of maggot debridement therapy as a treatment for chronic wounds through the review of several larval properties.

TARGET AUDIENCE

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES

After participating in this educational activity, the participant will be able to:

1. Summarize the use, process, and precautions for maggot debridement to treat chronic wounds.

2. Synthesize the results of the bibliographic review of the use of maggot debridement to treat chronic wounds.
Milrinone Acts as a Vasodilator But Not an Inotrope in Children After Cardiac Surgery—Insights From Wave Intensity Analysis
Authors: Rahiman Sarfaraz , Kowalski Remi , Kwok Sit Yee , Matha Sunit , Jones Bryn , Smolich Joseph J. , Mynard Jonathan P. , Butt Warwick , Millar Johnny
Published: September 2020

Objectives:

Milrinone is an inodilator widely used in the postoperative management of children undergoing cardiac surgery. The literature supporting its inotropic effect is sparse. We sought to study the effect of milrinone on the vasculature and its effects on the ventricular function using wave intensity analysis. We also intended to evaluate the feasibility of using wave intensity analysis by the bedside.

Design:

prospective single-center observational study.

Setting:

PICU of a tertiary children’s hospital.

Patients:

Children (< 18 yr) admitted to PICU following cardiac surgery who required to be commenced on a milrinone infusion.

Interventions:

Echocardiography and Doppler ultrasound assessments for wave intensity analysis were performed prior to commencing milrinone and 4–6 hours after milrinone infusion.

Measurements and Main Results:

Wave intensity analysis was successfully performed and analyzed in 15 of 16 patients (94%). We identified three waves—a forward compression wave, backward compression wave, and forward decompression wave. The waves were described with their cumulative intensity and wave-related pressure change. There was a 26% reduction in backward compression wave cumulative intensity following the introduction of milrinone. Other variables (backward compression wave cumulative intensity/forward compression wave cumulative intensity ratio, backward compression wave wave-related pressure change, backward compression wave wave-related pressure change/forward compression wave wave-related pressure change ratio) consistent with vasodilation also decreased after milrinone. It also decreased the vascular wavespeed by 7.1% and increased the distensibility of the vessels by 14.6%. However, it did not increase forward compression wave cumulative intensity, a variable indicating the systolic force generated by the ventricle. Forward decompression wave cumulative intensity indicating ventricular early diastolic relaxation also did not change.

Conclusions:

In a cohort of children recovering in PICU after having undergone cardiac surgery, we found that milrinone acted as a vasodilator but did not demonstrate an improvement in the contractility or an improved relaxation of the left ventricle as assessed by wave intensity analysis. We were able to demonstrate the feasibility and utility of wave intensity analysis to further understand ventriculo-vascular interactions in an intensive care setting.
Effects of combined 17β-estradiol and progesterone on weight and blood pressure in postmenopausal women of the REPLENISH trial
Authors: Black Denise R. , Minkin Mary Jane , Graham Shelli , Bernick Brian , Mirkin Sebastian
Published: September 2020

Objective:

To examine the impact of a single-capsule 17β-estradiol (E2)/progesterone (P4) on weight and blood pressure (BP) when treating moderate to severe vasomotor symptoms in postmenopausal women with a uterus.

Methods:

Healthy postmenopausal women with a uterus (aged 40-65, body mass index ≤34 kg/m2, BP ≤140/90 mm Hg) were randomized to daily E2/P4 (mg/mg; 1/100, 0.5/100, 0.5/50, 0.25/50) or placebo in the phase 3 REPLENISH trial (NCT01942668). Changes in weight and BP from baseline to month 12 were evaluated. Potentially clinically important changes were defined as increases or decreases from baseline in weight by ≥15% and ≥11.3 kg, systolic BP by ≥20 mm Hg (absolute value ≥160 or ≤90 mm Hg), and diastolic BP by ≥15 mm Hg (absolute value ≥90 or ≤60 mm Hg).

Results:

Overall mean changes in weight and BP from baseline to month 12 with E2/P4 were modest and generally not statistically or clinically significant versus placebo. Incidence of potentially clinically important changes was low for weight (E2/P4 vs placebo: 1.1-2.6% vs 2.2%), systolic BP (0.3-1.1% vs 1.1%), and diastolic BP (1.4-4.2% vs 3.2%). A small number of women had treatment-related, treatment-emergent adverse events of weight gain (1.4-2.6% vs 1.3%) or hypertension (0.2-1.2% vs 0%). Few women who discontinued E2/P4 had weight gain (1.6%) or hypertension (0.6%) as a primary reason. Efficacy profile on VMS was consistent with previous findings and not modified by body mass index.

Conclusions:

Twelve-month use of E2/P4 had no clinically meaningful impact on weight or BP in postmenopausal women of the REPLENISH study.
The Role of Sexually Transmitted Infections in Police as Clients Among Street-Based Female Sex Workers in Baltimore City
Authors: Sherman Susan G. , Nestadt Danielle Friedman , Silberzahn Bradley E. , Decker Michele , Park Ju Nyeong , Footer Katherine H.A.
Published: September 2020

Background

Research among street-based female sex workers (FSWs) has documented many harms caused by police. One harm that has received little attention is that of police as clients. We examined this interaction in a 12-month longitudinal cohort study of street-based FSWs in Baltimore, MD.

Methods

We explored longitudinal bivariate and multivariate associations between having police clients and independent variables that focused on sexually transmitted infections (STIs), as well as demographic, structural, substance use, police interaction, and violence-related factors.

Results

Mean participant age was 35.8 years, 65.9% were White, and more than half (53.3%) had less than a high school education. Most (70.3%) used heroin daily, and 24.8% reported having police as clients over the study period. In a multivariate model, factors independently associated with recent police clients were recent arrest (adjusted odds ratio [aOR], 1.76; 95% confidence interval [CI], 1.03–2.99; P = 0.037), coerced or forced sex by police (aOR, 4.47; 95% CI, 1.79–11.12; P = 0.001), higher number of egregious police practices experienced (aOR, 1.77; 95% CI, 1.38–2.29; P < 0.001), and prevalent STI infection (aOR, 2.43; 95% CI, 1.46–4.04; P = 0.001).

Conclusions

The study uniquely documents both the frequency with which street-based FSWs take police as clients and the role of egregious police practices and prevalent STIs in association with police as clients. Results indicate the police-as-client association as a form of “everyday violence,” which both normalizes and legitimizes police power and structural violence. Alongside the urgent need for decriminalization of sex work and STI prevention programs tailored for this complex population, prompt investigation and harsher penalties for police officers who engage in sex with FSW could help shift police culture away from abuse.
Changes in Scleral Tonometry and Anterior Chamber Angle after Short-term Scleral Lens Wear
Authors: Obinwanne Chukwuemeka Junior , Echendu Damian C. , Agbonlahor Osazee , Dike Stella
Published: September 2020

SIGNIFICANCE

Scleral lens wear can alter aqueous fluid and anterior chamber angle dynamics, leading to changes in intraocular pressure (IOP). However, there is limited information supporting this relationship between scleral lens wear, anterior chamber angle (ACA), and IOP changes in an black African population.

PURPOSE

The purpose of this study was to compare scleral IOP and ACA before, during, and after 4 hours of scleral lens wear in healthy neophyte scleral lens wearers from an black African population.

METHODS

This was a prospective study involving 20 eyes of 20 subjects with a mean ± standard deviation age of 28.7 ± 4.3 years. The study was divided into a screening and experimental phase. Scleral lenses from a diagnostic trial set were fit on a randomly selected eye. Scleral IOP was measured using a Schiotz tonometer (Winters, Jungingen, Germany) (weight, 7.5 g) on the superior-temporal sclera, and ACA was assessed using anterior segment optical coherence tomography on the temporal angle before scleral lens wear; at 10 minutes, 2 hours, and 4 hours during wear; and 10 minutes after scleral lens removal.

RESULTS

The mean ± standard deviation base curve of the scleral lens fit in the study eye was 43.4 ± 1.3 D with average tear reservoir thickness of 288.1 ± 122.0 μm at 4 hours. The mean scleral IOP before lens wear was 17.2 ± 3.5 mmHg, decreased to 16.4 ± 4.5 mmHg at 4 hours of scleral lens wear, and was 16.6 ± 3.5 mmHg 10 minutes after lens removal. The temporal ACA before scleral lens application was 43.0 ± 6.6° and varied during the 4 hours of scleral lens wear, ultimately increasing to 45.0 ± 5.4° at 10 minutes after scleral lens removal. The change in IOP and ACA was not statistically significant (F= 0.501,P= .74; andF= 2.399,P= .09, respectively).

CONCLUSIONS

Results suggest that 4 hours of nonfenestrated scleral lens wear did not have a significant impact on IOP or ACA in most of our study population.
Mechanisms of immune suppression by myeloid-derived suppressor cells: the role of interleukin-10 as a key immunoregulatory cytokine
Authors: Yaseen Mahmoud Mohammad , Abuharfeil Nizar Mohammad , Darmani Homa , Daoud Ammar
Published: September 2020

Chronic immune activation and inflammation are unwanted consequences of many pathological conditions, since they could lead to tissue damage and immune exhaustion, both of which can worsen the pathological condition status. In fact, the immune system is naturally equipped with immunoregulatory cells that can limit immune activation and inflammation. However, chronic activation of downregulatory immune responses is also associated with unwanted consequences that, in turn, could lead to disease progression as seen in the case of cancer and chronic infections. Myeloid-derived suppressor cells (MDSCs) are now considered to play a pivotal role in the pathogenesis of different inflammatory pathological conditions, including different types of cancer and chronic infections. As a potent immunosuppressor cell population, MDSCs can inhibit specific and non-specific immune responses via different mechanisms that, in turn, lead to disease persistence. One such mechanism by which MDSCs can activate their immunosuppressive effects is accomplished by secreting copious amounts of immunosuppressant molecules such as interleukin-10 (IL-10). In this article, we will focus on the pathological role of MDSC expansion in chronic inflammatory conditions including cancer, sepsis/infection, autoimmunity, asthma and ageing, as well as some of the mechanisms by which MDSCs/IL-10 contribute to the disease progression in such conditions.
Identification of putative calorie restriction mimetics using mammalian gene expression profiles
Authors: Vazquez Alexei
Published: September 2020

Obesity is a risk factor for cardiovascular diseases, diabetes and cancer. In theory, the obesity problem could be solved by the adherence to a calorie-restricted diet, but that is not generally achieved in practice. An alternative is a pharmacological approach, using compounds that trigger the same metabolic changes associated with calorie restriction. Here, I expand in the pharmacological direction by identifying compounds that induce liver gene signature profiles that mimic those induced by calorie restriction. Using gene expression profiles from mice and rat, I identify corticosteroids, PPAR agonists and some antibacterial/antifungal as candidate compounds mimicking the response to calorie restriction in the liver gene signatures.