bluuebunny/crossref_metadata_2025 huggingface dataset:
Deterioration of nature's information webs in the Anthropocene
Authors: Szymkowiak Jakub , Schmidt Kenneth A.
Published: September 2021

Information use constitutes the key aspect of phenotype–environment interactions for any organism living in a heterogeneous environment, as information increases the chances of making the decisions that match the current perceived state of the world. Information use is ubiquitous in a variety of contexts and organisms throughout their lifetime are inter‐woven into complex information webs, in which information is constantly produced, gained and transmitted among conspecifics and heterospecifics. Due to increasingly disruptive anthropogenic changes to the Earth's support system, this information dimension of individuals' lives is now being increasingly deteriorated by human‐induced rapid environmental changes. Here, we argue that one of the more pressing challenges for the field of the Ecology of Information – the study of how organisms acquire and use information and the ecological significance of informed decision‐making – is to expand the current framework and strengthen its bridge to conservation biology. Building on recent theoretical and empirical advances in the field of Ecology of Information, we first emphasize the far‐reaching ecological ramifications of information use and provide an overview of how individuals' informed decision‐making scales up to affect population and community dynamics. Next, we highlight how recent human‐induced rapid environmental changes deteriorate information acquisition, use and transmission in natural systems, thereby disrupting nature's information webs. The omission of information from conservation actions can have largely detrimental effects. Thus, there is an urgent need for ecologists and conservation biologists to explicitly trace and quantify the flows of information in ecological systems, and the diversity of information sources used by living organisms for decision‐making and to establish collective efforts to preserve nature's information webs.
A prospective observational study on the feasibility of subumbilical laparoscopic procedures under epidural anesthesia in sedated spontaneously breathing infants with a natural airway
Authors: Opfermann Philipp , Marhofer Peter , Springer Alexander , Metzelder Martin , Zadrazil Markus , Schmid Werner
Published: September 2021

Background

Laparoscopic procedures are usually performed under general anesthesia with a secured airway including endotracheal intubation or supraglottic airways.

Aims

This is a prospective study of the feasibility of subumbilical laparoscopic procedures under epidural anesthesia in sedated, spontaneous breathing infants with a natural airway.

Methods

We consecutively enrolled 20 children <3 years old with nonpalpable testes scheduled for diagnostic laparoscopy with or without an ensuing orchidopexy, inguinal revision, or Fowler‐Stephens maneuver. Inhalational induction for venous access was followed by sedation with propofol and ultrasound‐guided single‐shot epidural anesthesia via the caudal or thoracolumbar approach using 1.0 or 0.5 ml kg−1 ropivacaine 0.38%, respectively. The primary outcome measure was block success, defined as no increase in heart rate by >15% or other indicators of pain upon skin incision.

Results

Of the 20 children (median age: 10 months; IQR: 8.3−12), 17 (85%) were anesthetized through a caudal and 3 (15%) through a direct thoracolumbar epidural, 18 (90%) underwent a surgical procedure and 2 (10%) diagnostic laparoscopy only. Five patients (25%) received block augmentation using an intravenous bolus of fentanyl (median dose: 0.9 µg kg−1; IQR: 0.8−0.95) after the initial prick test and before skin incision. There was no additional need for systemic pain therapy in the operating theater or recovery room. No events of respiratory failure or aspiration were observed.

Conclusions

In experienced hands, given our success rate of 100%, epidural anesthesia performed in sedated spontaneously breathing infants with a natural airway can be an alternative strategy for subumbilical laparoscopic procedures.
Peace as Intrinsic Value: The Pacifist Intuition and Intuitive Pacifism
Authors: Fiala Andrew
Published: September 2021

Those who think of peace as an intrinsic value might be called “intuitionist pacifists” or “intuitive pacifists.” For pacifists of this sort, peace functions as an unanalyzable foundational value. The pacifist intuition is often meta‐ethical and not the result of argument or inference. Understanding pacifism in this way helps explain some disputes between pacifism and its critics. The article makes this argument with appeal to historical sources, both in the literature on pacifism and in the literature on intuitionism. It contributes to our understanding of the history of pacifism, while also offering a pacifist contribution to the theory of intuitionism.
Social Public Purchasing: Addressing a Critical Void in Public Purchasing Research
Authors: Hafsa Fatima , Darnall Nicole , Bretschneider Stuart
Published: September 2021

Since governments are the largest buyers globally, they have enormous purchasing power. Government purchasing, therefore, has potential to be leveraged to improve social outcomes, such as helping disadvantaged communities, ensuring labor rights, and minimizing negative environmental impacts. However, as yet, there is little understanding about social public purchasing research in the field of public administration. We provide a theoretical framework for organizing research around social public purchasing. We then survey both the scholarly and practitioner research on social public purchasing in order to develop a clear understanding of the critical knowledge gaps and the potential for important social public purchasing research.
Tests of multivariate copula exchangeability based on Lévy measures
Authors: Bahraoui Tarik , Quessy Jean‐François
Published: September 2021

This paper introduces tests for the symmetry of the copula of random vector. The proposed statistics are based on the copula characteristic function and the weight function that appears naturally in their definition are assumed to belong to the general family of Lévy measures. The proposed test statistics are rank‐based and expresses as weighted ‐norms computed from a vector of empirical copula characteristic functions. Their nondegenerate asymptotic distributions under the null hypothesis and general alternatives, as well as the validity of a multiplier bootstrap for the computation of p‐values, are derived using nonstandard arguments. Extended Monte–Carlo experiments show that the new tests hold their size well and are powerful against a wide range of alternatives, and appear to be more powerful than a Cramér–von Mises test based on empirical copulas.
Long‐term vision outcomes and breed differences of Ahmed Glaucoma Valve implantation in 132 eyes of 122 dogs
Authors: Saito Akihiko , Iwashita Hiroko , Kazama Yoshiyuki , Wakaiki Shinsuke
Published: September 2021

Objective

To evaluate the long‐term vision outcomes of Ahmed glaucoma valve (AGV) implantation in dogs.

Procedures

The medical records of dogs that underwent AGV implantation from January 2010 to December 2019 were reviewed to assess the duration of post‐surgical vision preservation (PVP). The relationship between PVP and the underlying cause of glaucoma, implant placement, and preoperative intraocular pressure was evaluated.

Results

One hundred and thirty‐two eyes of 122 dogs (mean age, 8.3 ± 2.6 years) were included. The mean ± standard error of PVP for all eyes was 57.5 ± 3.9 months. PVP in the dogs with primary acute glaucoma and prior history of cataract surgery was 56.4 ± 4.7 and 59.3 ± 5.9 months, respectively (p = .712). The PVP of the Shiba Inu, American Cocker Spaniel, and other breeds was 63.1 ± 5.5, 33.7 ± 5.3, and 59.1 ± 6.3 months, respectively (p < .05). The PVP in dogs with medial implantation was 61.9 ± 4.7 months, and in those with lateral implantation was 45.4 ± 6.4 months (p = .034). Among the 132 eyes investigated, 48 (36.4%) lost vision by the last follow‐up, and 18 eyes retained vision for more than 5 years. Two of the total number of eyes retained their vision for more than 8 years.

Conclusions

The vision outcomes regarding the use of AGV for the management of canine glaucoma were favorable in dogs.
Humero‐anconeal elbow incongruity in spaniel breed dogs with humeral intracondylar fissure: Arthroscopic findings
Authors: Danielski Alan , Yeadon Russell
Published: September 2021

Objective

To report arthroscopic findings in dogs with humeral intracondylar fissure (HIF) and compare these findings in joints of dogs not affected by HIF on preoperative CT images.

Study design

Controlled clinical study.

Animals

Dogs with HIF (14 dogs, 21 elbows) and dogs without HIF (20 dogs, 31 elbows).

Methods

A caudo‐medial arthroscope portal was used to inspect all elbow joints. Arthroscopic features of 21 joints of dogs with HIF were compared with 31 control elbows of HIF‐ negative dogs.

Results

All elbows with HIF showed a focal cartilage lesion on the caudal aspect of the humeral condyle. The lesions ranged from a simple indentation into the articular surface to a full thickness cartilage erosion. Humero‐anconeal incongruity was identified in all elbows with HIF as absence of joint space at the point of contact between the tip of the anconeal process and the cartilage lesion, with a wider joint space distally within the ulnar trochlear notch. None of the elbows without HIF showed the cartilage lesion or evidence of humero‐anconeal incongruity.

Conclusion

Use of a novel arthroscope portal allowed description of a previously unreported cartilage lesion on the caudal humeral condyle of dogs with HIF. The lesion was found in all dogs with HIF but in no dogs without HIF.

Clinical significance

Humero‐anconeal incongruity and an associated cartilage lesion appear to be present in dogs with HIF. We propose that this lesion may be associated with humero‐anconeal incongruity. This may be considered as a possible future therapeutic target for HIF.
Accommodation of Multishaft Gas Turbine Switching Control Gain Tuning Problem to Inlet Guide Vane Position
Authors: Ma Yujia , Liu Jinfu , Zhu Linhai , Li Qi , Liu Huanpeng , Yu Daren
Published: September 2021

This article aims to discuss the influence of compressor inlet guide vane (IGV) position on gas turbine switching control system gain tuning problem. The distinction between IGV and normally reckoned working conditions is differentiated, and an improved double-layer linear parameter varying (LPV) model is proposed to estimate the protected parameters under various IGV positions. Controller gain tuning is conducted with single and multi-objective intellectual optimization algorithms. Simulation results reveal that normally used multi-objective optimization procedure is unnecessary and time-consuming. While with the comprehensive indicator introduced in this paper, the calculation burden can be greatly eased. This improvement is especially advantageous when tuning work is carried out under multiple IGV positions.
Virtual Gas Turbines Part I: A Top-Down Geometry Modeling Environment for Turbomachinery Application
Authors: Kulkarni Davendu , Lu Gan , Wang Feng , Mare Luca di
Published: September 2021

The gas turbine engine design involves multidisciplinary, multifidelity iterative design-analysis processes. These highly intertwined processes are nowadays incorporated in automated design frameworks to facilitate high-fidelity, fully coupled, large-scale simulations. The most tedious and time-consuming step in such simulations is the construction of a common geometry database that ensures geometry consistency at every step of the design iteration, is accessible to multidisciplinary solvers, and allows system-level analysis. This paper presents a novel design-intent-driven geometry modeling environment that is based on a top-down feature-based geometry model generation method. The geometry features in this modeling environment are organized in a turbomachinery feature taxonomy. They produce a tree-like logical structure representing the engine geometry, wherein abstract features outline the engine architecture, while lower-level features define the detailed geometry. This top-down flexible feature-tree arrangement enables the design intent to be preserved throughout the design process, allows the design to be modified freely, and supports the design intent variations to be propagated throughout the geometry model automatically. The application of the proposed feature-based geometry modeling environment is demonstrated by generating a whole-engine computational geometry model. This geometry modeling environment provides an efficient means of rapidly populating complex turbomachinery assemblies. The generated engine geometry is fully scalable, easily modifiable, and is re-usable for generating the geometry models of new engines or their derivatives. This capability also enables fast multifidelity simulation and optimization of various gas turbine systems.
Optoelectronic performance characterization of MoS2 photodetectors for low frequency sensing applications
Authors: Ki Seungjun , Chen Mingze , Liang Xiaogan
Published: September 2021

The specific advantages of implementing MoS2 and other layered semiconductors for optoelectronic biosensing and other relevant photodetection applications remain unclear. In this work, we investigate the photoresponsivity and noise characteristics of in-plane MoS2 photodetectors. This work indicates that MoS2 photodetectors exhibit lower noise equivalent power (NEP) and detectivity (D*) in comparison with commercial CdS photodetectors. In addition, the low-frequency NEP and D* values of MoS2 photodetectors exhibit a prominent dependence on the MoS2 photoactive layer thickness. We have identified the optimal MoS2 thickness in the range of 8–30 nm. We also study the photoresponse characteristics of optimized MoS2 photodetectors at several different wavelengths that are important for clinical colorimetry assays. Such an optimized photodetector shows a maximum photoresponsivity of 164.3 A/W and a minimum NEP of 3.99 × 10−17 W/Hz1/2 (and a D* of 5.01 × 1010 J) with relative variance less than 14%. This work provides a useful guideline for optimizing the photoresponse characteristics of MoS2-based optoelectronic devices, which is critical to practical low-frequency optoelectronic biosensing applications.
Toothed whale auditory brainstem responses measured with a non-invasive, on-animal tag
Authors: Smith Adam B. , Madsen Peter T. , Johnson Mark , Tyack Peter , Wahlberg Magnus
Published: September 2021

Empirical measurements of odontocete hearing are limited to captive individuals, constituting a fraction of species across the suborder. Data from more species could be available if such measurements were collected from unrestrained animals in the wild. This study investigated whether electrophysiological hearing data could be recorded from a trained harbor porpoise (Phocoena phocoena) using a non-invasive, animal-attached tag. The results demonstrate that auditory brainstem responses to external and self-generated stimuli can be measured from a stationary odontocete using an animal-attached recorder. With additional development, tag-based electrophysiological platforms may facilitate the collection of hearing data from freely swimming odontocetes in the wild.
SIRPα sequesters SHP-2 to promote IL-4 and IL-13 signaling and the alternative activation of macrophages
Authors: Shi Lei , Kidder Koby , Bian Zhen , Chiang Samantha Kuon Ting , Ouellette Corbett , Liu Yuan
Published: September 2021

SIRPα enhances macrophage alternative activation by preventing a phosphatase from acting on cytokine receptors.
Hypermodified DNA in Viruses of E.coli and Salmonella
Authors: Hutinet Geoffrey , Lee Yan-Jiun , de Crécy-Lagard Valérie , Weigele Peter R.
Published: September 2021

The DNA in bacterial viruses collectively contains a rich, yet relatively underexplored, chemical diversity of nucleobases beyond the canonical adenine, guanine, cytosine, and thymine. Herein, we review what is known about the genetic and biochemical basis for the biosynthesis of complex DNA modifications, also called DNA hypermodifications, in the DNA of tailed bacteriophages infecting
Escherichia coli
and
Salmonella enterica
.
Across Functional Boundaries: Making Nonneutralizing Antibodies To Neutralize HIV-1 and Mediate Fc-Mediated Effector Killing of Infected Cells
Authors: Richard Jonathan , Nguyen Dung N. , Tolbert William D. , Gasser Romain , Ding Shilei , Vézina Dani , Yu Gong Shang , Prévost Jérémie , Gendron-Lepage Gabrielle , Medjahed Halima , Gottumukkala Suneetha , Finzi Andrés , Pazgier Marzena
Published: September 2021

Highly conserved epitopes within the coreceptor binding site (CoRBS) and constant region 1 and 2 (C1-C2 or cluster A) are only available for antibody recognition after the HIV-1 Env trimer binds host cell CD4; therefore, they are not accessible on virions and infected cells, where the expression of CD4 is downregulated. Here, we have developed new antibody fusion molecules in which domains 1 and 2 of soluble human CD4 are linked with monoclonal antibodies of either the CoRBS or cluster A specificity.
Microbial Ecology and Evolution Are Essential for Understanding Pandemics
Authors: Frederickson Megan E. , Reese Aspen T.
Published: September 2021

Ecology and evolution, especially of microbes, have never been more relevant than in our global fight against SARS-CoV-2, the virus that causes COVID-19. Understanding how populations of SARS-CoV-2 grow, disperse, and evolve is of critical importance to managing the COVID-19 pandemic, and these questions are fundamentally ecological and evolutionary in nature.
Streptococcus pyogenes Forms Serotype- and Local Environment-Dependent Interspecies Protein Complexes
Authors: Chowdhury Sounak , Khakzad Hamed , Bergdahl Gizem Ertürk , Lood Rolf , Ekstrom Simon , Linke Dirk , Malmström Lars , Happonen Lotta , Malmström Johan
Published: September 2021

Streptococcus pyogenes
(group A
Streptococcus
[GAS]), is a human-specific Gram-positive bacterium. Each year, the bacterium affects 700 million people globally, leading to 160,000 deaths.
Agricultural Management Affects the Active Rhizosphere Bacterial Community Composition and Nitrification
Authors: Bay Guillaume , Lee Conard , Chen Chiliang , Mahal Navreet K. , Castellano Michael J. , Hofmockel Kirsten S. , Halverson Larry J.
Published: September 2021

Crops in simplified, low-diversity agroecosystems assimilate only a fraction of the inorganic nitrogen (N) fertilizer inputs. Much of this N fertilizer is lost to the environment as N oxides, which degrade water quality and contribute to climate change and loss of biodiversity.
BiG-MAP: an Automated Pipeline To Profile Metabolic Gene Cluster Abundance and Expression in Microbiomes
Authors: Pascal Andreu Victória , Augustijn Hannah E. , van den Berg Koen , van der Hooft Justin J. J. , Fischbach Michael A. , Medema Marnix H.
Published: September 2021

Microbes play an increasingly recognized role in determining host-associated phenotypes by producing small molecules that interact with other microorganisms or host cells. The production of these molecules is often encoded in syntenic genomic regions, also known as gene clusters.
Periodically Disturbing the Spatial Structure of Biofilms Can Affect the Production of an Essential Virulence Factor in
Pseudomonas aeruginosa
Authors: Quinn Rebecca J. , Barraza Ivana , García-Diéguez Laura , Pajon Camryn , Krausfeldt Lauren E. , Ibrahim Kerollos , Enzinna Laura A. , Thorn Morgan E. , Eldakar Omar Tonsi , Craddock Travis J. A. , Smith Robert P.
Published: September 2021

Virulence factors are required to cause infections. Previous work has shown that the spatial organization of a population, such as a biofilm, can increase the production of some virulence factors, including pyoverdine, which is produced by
Pseudomonas aeruginosa
.
COVID-19 Pandemic and Exercise (COPE) trial: a multigroup pragmatic randomised controlled trial examining effects of app-based at-home exercise programs on depressive symptoms
Authors: Puterman Eli , Hives Benjamin , Mazara Nicole , Grishin Nikol , Webster Joshua , Hutton Stacey , Koehle Michael Stephen , Liu Yan , Beauchamp Mark R
Published: September 2021

Background

The number of adults across the globe with significant depressive symptoms has grown substantially during the COVID-19 pandemic. The extant literature supports exercise as a potent behaviour that can significantly reduce depressive symptoms in clinical and non-clinical populations.

Objective

Using a suite of mobile applications, at-home exercise, including high intensity interval training (HIIT) and/or yoga, was completed to reduce depressive symptoms in the general population in the early months of the pandemic.

Methods

A 6-week, parallel, multiarm, pragmatic randomised controlled trial was completed with four groups: (1) HIIT, (2) Yoga, (3) HIIT+yoga, and (4) waitlist control (WLC). Low active, English-speaking, non-retired Canadians aged 18–64 years were included. Depressive symptoms were measured at baseline and weekly following randomisation.

Results

A total of 334 participants were randomised to one of four groups. No differences in depressive symptoms were evident at baseline. The results of latent growth modelling showed significant treatment effects in depressive symptoms for each active group compared with the WLC, with small effect sizes (ESs) in the community-based sample of participants. Treatment groups were not significantly different from each other. Effect sizes were very large (eg, week 6 ES range=−2.34 to −2.52) when restricting the analysis only to participants with high depressive symptoms at baseline.

Conclusions

At-home exercise is a potent behaviour to improve mental health in adults during the pandemic, especially in those with increased levels of depressive symptoms. Promotion of at-home exercise may be a global public health target with important personal, social and economic implications as the world emerges scathed by the pandemic.

Trial registration number

NCT04400279.
Social determinants of health impacting adherence to diabetic retinopathy examinations
Authors: Cai Cindy X , Li Yixuan , Zeger Scott L , McCarthy Melissa L
Published: September 2021

Introduction

This study evaluates the association of multidimensional social determinants of health (SDoH) with non-adherence to diabetic retinopathy examinations.

Research design and methods

This was a post-hoc subgroup analysis of adults with diabetes in a prospective cohort study of enrollees in the Washington, DC Medicaid program. At study enrollment, participants were given a comprehensive SDoH survey based on the WHO SDoH model. Adherence to recommended dilated diabetic retinopathy examinations, as determined by qualifying Current Procedural Terminology codes in the insurance claims, was defined as having at least one eye examination in the 2-year period following study enrollment.

Results

Of the 8943 participants enrolled in the prospective study, 1492 (64% female, 91% non-Hispanic Black) were included in this post-hoc subgroup analysis. 47.7% (n=712) were adherent to the recommended biennial diabetic eye examinations. Not having a regular provider (eg, a primary care physician) and having poor housing conditions (eg, overcrowded, inadequate heating) were associated with decreased odds of adherence to diabetic eye examinations (0.45 (95% CI 0.31 to 0.64) and 0.70 (95% CI 0.53 to 0.94), respectively) in the multivariate logistic regression analysis controlling for age, sex, race/ethnicity, overall health status using the Chronic Disability Payment System, diabetes severity using the Diabetes Complications Severity Index, history of eye disease, and history of diabetic eye disease treatment.

Conclusions

A multidimensional evaluation of SDoH revealed barriers that impact adherence to diabetic retinopathy examinations. Having poor housing conditions and not having a regular provider were associated with poor adherence. A brief SDoH assessment could be incorporated into routine clinical care to identify social risks and connect patients with the necessary resources to improve adherence to diabetic retinopathy examinations.
Excess deaths reveal unequal impact of COVID-19 in Ecuador
Authors: Cuéllar Leticia , Torres Irene , Romero-Severson Ethan , Mahesh Riya , Ortega Nathaniel , Pungitore Sarah , Ke Ruian , Hengartner Nicolas
Published: September 2021

Latin America has struggled to control the transmission of COVID-19. Comparison of excess death (ED) rates during the pandemic reveals that Ecuador is among the highest impacted countries. In this analysis, we update our previous findings with the most complete all-cause mortality records available for 2020, disaggregated by sex, age, ethnicity and geography. Our study shows that in 2020, Ecuador had a 64% ED rate (95% CI 63% to 65%) or 64% more deaths than expected. Men had a higher ED rate, 75% (95% CI 73% to 76%), than women’s 51% (95% CI 49% to 52%), and this pattern of higher EDs for men than women held for most age groups. The only exception was the 20–29 age group, where women had 19% more deaths, compared to 10% more deaths for men, but that difference is not statistically significant. The analysis provides striking evidence of the lack of COVID-19 diagnostic testing in Ecuador: the confirmed COVID-19 deaths in 2020 accounted for only 21% of total EDs. Our significant finding is that indigenous populations, who typically account for about 5% of the deaths, show almost four times the ED rate of the majority mestizo group. Indigenous women in each age group have higher ED rates than the general population and, in ages between 20 and 49 years, they have higher ED rates than indigenous men. Indigenous women in the age group 20–29 years had an ED rate of 141%, which is commensurate to the ED rate of indigenous women older than 40 years.
The role of trained champions in sustaining and spreading nutrition care improvements in hospital: qualitative interviews following an implementation study
Authors: Laur Celia , Bell Jack , Valaitis Renata , Ray Sumantra , Keller Heather
Published: September 2021

Background

Many patients are already malnourished when admitted to hospital. Barriers and facilitators to nutrition care in hospital have been identified and successful interventions developed; however, few studies have explored how to sustain and spread improvements. The More-2-Eat phase 1 study involved five hospitals across Canada implementing nutrition care improvements, while phase 2 implemented a scalable model using trained champions, audit and feedback, a community of practice with external mentorship and an implementation toolkit in 10 hospitals (four continuing from phase 1). Process measures showed that screening and assessment from phase 1 were sustained for at least 4 years. The objective of this study was to help explain how these nutrition care improvements were sustained and spread by understanding the role of the trained champions, and to confirm and expand on themes identified in phase 1.

Methods

Semistructured telephone interviews were conducted with champions from each phase 2 hospital and recordings transcribed verbatim. To explore the champion role, transcripts were deductively coded to the 3C model of Concept, Competence and Capacity. Phase 2 transcripts were also deductively coded to themes identified in phase 1 interviews and focus groups.

Results

Ten interviews (n=14 champions) were conducted. To sustain and spread nutrition care improvements, champions needed to understand theConceptsof change management, implementation, adaptation, sustainability and spread in order to embed changes into routine practice. Champions also needed theCompetence, including the skills to identify, support and empower new champions, thus sharing the responsibility.Capacity, including time, resources and leadership support, was the most important facilitator for staying engaged, and the most challenging. All themes identified in qualitative interviews in phase 1 were applicable 4 years later and were mentioned by new phase 2 hospitals. There was increased emphasis on audit and feedback, and the need for standardisation to support embedding into current practice.

Conclusion

Trained local champions were required for implementation. By understanding key concepts, with appropriate and evolving competence and capacity, champions supported sustainability and spread of nutrition care improvements. Understanding the role of champions in supporting implementation, spread and sustainability of nutrition care improvements can help other hospitals when planning for and implementing these improvements.

Trial registration number

NCT02800304,NCT03391752.
Molecular characterisation of pancreatic ductal adenocarcinoma withNTRKfusions and review of the literature
Authors: Allen Michael J , Zhang Amy , Bavi Prashant , Kim Jaeseung C , Jang Gun Ho , Kelly Deirdre , Perera Sheron , Denroche Rob E , Notta Faiyaz , Wilson Julie M , Dodd Anna , Ramotar Stephanie , Hutchinson Shawn , Fischer Sandra E , Grant Robert C , Gallinger Steven , Knox Jennifer J , O'Kane Grainne M
Published: September 2021

Aims

The majority of pancreatic ductal adenocarcinomas (PDACs) harbour oncogenic mutations inKRASwith variants inTP53,CDKN2AandSMAD4also prevalent. The presence of oncogenic fusions includingNTRKfusions are rare but important to identify. Here we ascertain the prevalence ofNTRKfusions and document their genomic characteristics in a large series of PDAC.

Methods

Whole genome sequencing and RNAseq were performed on a series of patients with resected or locally advanced/metastatic PDAC collected between 2008 and 2020 at a single institution. A subset of specimens underwent immunohistochemistry (IHC) analysis. Clinical and molecular characterisation and IHC sensitivity and specificity were evaluated.

Results

400 patients were included (resected n=167; locally advanced/metastatic n=233). Three patients were identified as harbouring anNTRKfusion, twoEML4-NTRK3(KRAS-WT) and a single novelKANK1-NTRK3fusion. The latter occurring in the presence of a subclonalKRASmutation. Typical PDAC drivers were present including mutations inTP53andCDKN2A. Substitution base signatures and tumour mutational burden were similar to typical PDAC. The prevalence ofNTRKfusions was 0.8% (3/400), while inKRASwild-type tumours, it was 6.25% (2/32). DNA prediction alone documented six false-positive cases. RNA analysis correctly identified the in-frame fusion transcripts. IHC analysis was negative in theKANK1-NTRK3fusion but positive in aEML4-NTRK3case, highlighting lower sensitivity of IHC.

Conclusion

NTRKfusions are rare; however, with emerging therapeutic options targeting these fusions, detection is vital. Reflex testing forKRASmutations and subsequent RNA-based screening could help identify these cases in PDAC.
Frequency of microsatellite instability (MSI) in upper tract urothelial carcinoma: comparison of the Bethesda panel and the Idylla MSI assay in a consecutively collected, multi-institutional cohort
Authors: Kullmann Friederike , Strissel Pamela L , Strick Reiner , Stoehr Robert , Eckstein Markus , Bertz Simone , Wullich Bernd , Sikic Danijel , Wach Sven , Taubert Helge , Olbert Peter , Heers Hendrik , Lara María Fernanda , Macias Maria Luisa , Matas-Rico Elisa , Lozano Maria José , Prieto Daniel , Hierro Isabel , van Doeveren Thomas , Bieche Ivan , Masliah-Planchon Julien , Beaurepere Romane , Boormans Joost L , Allory Yves , Herrera-Imbroda Bernardo , Hartmann Arndt , Weyerer Veronika
Published: September 2021

Aims

Upper tract urothelial carcinoma (UTUC) is a rare malignancy with a poor prognosis which occurs sporadically or in few cases results from a genetic disorder called Lynch syndrome. Recently, examination of microsatellite instability (MSI) has gained importance as a biomarker: MSI tumours are associated with a better response to immunomodulative therapies. Limited data are known about the prevalence of MSI in UTUC. New detection methods using the fully automated Idylla MSI Assay facilitate analysis of increased patient numbers.

Methods

We investigated the frequency of MSI in a multi-institutional cohort of 243 consecutively collected UTUC samples using standard methodology (Bethesda panel), along with immunohistochemistry of mismatch repair (MMR) proteins. The same tumour cohort was retested using the Idylla MSI Assay by Biocartis.

Results

Using standard methodology, 230/243 tumours were detected as microsatellite stable (MSS), 4/243 tumours as MSI and 9/243 samples as invalid. In comparison, the Idylla MSI Assay identified four additional tumours as MSS, equalling 234/243 tumours; 4/243 were classified as MSI and only 5/243 cases as invalid. At the immunohistochemical level, MSI results were supported in all available cases with a loss in MMR proteins. The overall concordance between the standard and the Idylla MSI Assay was 98.35%. Time to result differed between 3 hours for Idylla MSI Assay and 2 days with the standard methodology.

Conclusion

Our data indicate a low incidence rate of MSI tumours in patients with UTUC. Furthermore, our findings highlight that Idylla MSI Assay can be applied as an alternative method of MSI analysis for UTUC.
Homelessness in early adulthood and biomedical risk factors by middle-age: the 1970 British Cohort Study
Authors: White James W , Hamer Mark , Batty G David
Published: September 2021

Background

Homelessness has been linked to premature mortality but the relationship with biomedical risk factors is uncertain.

Methods

We analysed data from 8581 participants in the 1970 British Birth Cohort Study. Homelessness and type of experience were self-reported at 30 years of age. Nine biomarkers outcomes were collected at 46 years of age: body mass index (BMI), blood pressure, total and high-density cholesterol, triglycerides, glycated haemoglobin, C-reactive protein (CRP), insulin-like growth factor 1 and we computed the 10-year risk for coronary heart disease.

Results

By 30 years of age, 5.8% of participants had been homeless with sofa surfing the most common experience (4.3%). Homelessness was associated with socioeconomic disadvantage, mental health problems and substance use in early adulthood, but these differences were not expressed in biomarkers. After accounting for early adulthood characteristics, residing in a bed and breakfast was associated with a higher BMI (0.59, 95% CI 0.13 to 1.05) and CRP (0.16, 95% CI 0.04 to 0.29), squatting with a lower BMI (−1.69, 95% CI –3.08 to −0.21) and rough sleeping with a higher 10-year risk of coronary heart disease (0.03, 95% CI 0.01 to 0.05).

Conclusions

Exposure to homelessness in early adulthood was essentially unrelated to biomarkers in middle age. Inconsistent links were found for specific types of experience.
Longitudinal thalamic white and grey matter changes associated with visual hallucinations in Parkinson’s disease
Authors: Zarkali Angeliki , McColgan Peter , Leyland Louise Ann , Lees Andrew John , Weil Rimona Sharon
Published: September 2021

Objective

Visual hallucinations are common in Parkinson’s disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical in controlling cortical networks, structural thalamic changes could underlie network dysfunction in PD hallucinations.

Methods

We used whole-brain fixel-based analysis and cortical thickness measures to examine longitudinal white and grey matter changes in 76 patients with PD (15 hallucinators, 61 non-hallucinators) and 26 controls at baseline, and after 18 months. We compared white matter and cortical thickness, adjusting for age, gender, time-between-scans and intracranial volume. To assess thalamic changes, we extracted volumes for 50 thalamic subnuclei (25 each hemisphere) and mean fibre cross-section (FC) for white matter tracts originating in each subnucleus and examined longitudinal change in PD-hallucinators versus non-hallucinators.

Results

PD hallucinators showed white matter changes within the corpus callosum at baseline and extensive posterior tract involvement over time. Less extensive cortical thickness changes were only seen after follow-up. White matter connections from the right medial mediodorsal magnocellular thalamic nucleus showed reduced FC in PD hallucinators at baseline followed by volume reductions longitudinally. After follow-up, almost all thalamic subnuclei showed tract losses in PD hallucinators compared with non-hallucinators.

Interpretation

PD hallucinators show white matter loss particularly in posterior connections and in thalamic nuclei, over time with relatively preserved cortical thickness. The right medial mediodorsal thalamic nucleus shows both connectivity and volume loss in PD hallucinations. Our findings provide mechanistic insights into the drivers of network imbalance in PD hallucinations and potential therapeutic targets.
Ventricular–vascular coupling is predictive of adverse clinical outcome in paediatric pulmonary arterial hypertension
Authors: Dufva Melanie J , Ivy Dunbar , Campbell Kristen , Lam Aimee , Rauff Adam , Breeman Karel T N , Douwes Johannes M , Berger Rolf M F , Kheyfets Vitaly Oleg , Hunter Kendall
Published: September 2021

Aims

Ventricular–vascular coupling, the ratio between the right ventricle’s contractile state (Ees) and its afterload (Ea), may be a useful metric in the management of paediatric pulmonary arterial hypertension (PAH). In this study we assess the prognostic capacity of the ventricular–vascular coupling ratio (Ees/Ea) derived using right ventricular (RV) pressure alone in children with PAH.

Methods

One hundred and thirty paediatric patients who were diagnosed with PAH via right heart catheterisation were retrospectively reviewed over a 10-year period. Maximum RV isovolumic pressure and end-systolic pressure were estimated using two single-beat methods from Takeuchiet al(Ees/Ea_(Takeuchi)) and from Kindet al(Ees/Ea_(Kind)) and used with an estimate of end-systolic pressure to compute ventricular–vascular coupling from pressure alone. Patients were identified as either idiopathic/hereditary PAH or associated PAH (IPAH/HPAH and APAH, respectively). Haemodynamic data, clinical functional class and clinical worsening outcomes—separated into soft (mild) and hard (severe) event categories—were assessed. Adverse soft events included functional class worsening, syncopal event, hospitalisation due to a proportional hazard-related event and haemoptysis. Hard events included death, transplantation, initiation of prostanoid therapy and hospitalisation for atrial septostomy and Pott’s shunt. Cox proportional hazard modelling was used to assess whether Ees/Eawas predictive of time-to-event.

Results

In patients with IPAH/HPAH, Ees/Ea_(Kind) and Ees/Ea_(Takeuchi) were both independently associated with time to hard event (p=0.003 and p=0.001, respectively) and when adjusted for indexed pulmonary vascular resistance (p=0.032 and p=0.013, respectively). Neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to soft event. In patients with APAH, neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to hard event or soft event.

Conclusions

Ees/Eaderived from pressure alone is a strong independent predictor of adverse outcome and could be a potential powerful prognostic tool for paediatric PAH.
District-scale numerical analysis of settlements related to groundwater lowering in variable soil conditions
Authors: Peduto Dario , Prosperi Alfonso , Nicodemo Gianfranco , Korff Mandy
Published: September 2021

This study presents a novel framework in which numerical modelling contributes to the performance of district-scale, subsidence-induced damage assessment in cities where ground settlements affect entire quarters. Therein, the implementation of expeditious procedures offers geotechnical engineers the possibility of contributing beyond the typical site scale. For this purpose, several “typified” hydro-geomechanical-loading (HGL) models, which represent (simplified) scenarios of masonry buildings undergoing settlements, were set up to account for different predisposing or triggering factors (i.e., soil heterogeneity, loading conditions, and groundwater variations) of settlement occurrence in built-up areas. These models exploit multi-source, wide-area input datasets encompassing the hydro-mechanical properties of geomaterials, in situ investigations and measurements (e.g., groundwater levels in wells), and innovative remote sensing data (i.e., DInSAR techniques). With reference to a district in Rotterdam City (the Netherlands), which was built on “soft soils”, the numerical simulations of different scenarios (i) provide an overview of the comparative role of predisposing or triggering factors on settlement occurrence and (ii) allow assessments of the expected induced damage to masonry buildings over 30 years with the exploitation of fragility curves. Considering the widespread diffusion of such geohazards, the proposed approach could help prioritise (rather expensive) maintenance work to the built heritage within sustainable strategies for subsidence risk mitigation.
The Relationship between Product Complexity and Exchange Rate Elasticities: Evidence from the People’s Republic of China’s Manufacturing Industries
Authors: THORBECKE WILLEM , CHEN CHEN , SALIKE NIMESH
Published: September 2021

More complex products are less substitutable in international trade and may therefore have lower price elasticities. We investigate this issue using 960 types of manufactured exports from the People’s Republic of China (PRC) to 190 partner economies disaggregated at the Harmonized System 4-digit level. We measure complexity using Hidalgo and Hausmann’s (2009) product complexity index. We find that price elasticities are lower for more complex goods. These results imply that the PRC can reduce its exporters’ exposure to tariffs, trade wars, and exchange rate volatility by upgrading its export basket.
On the Two Catching-Up Mechanisms in Asian Development
Authors: KUNIEDA TAKUMA , OKADA KEISUKE , SAWADA YASUYUKI , SHIBATA AKIHISA
Published: September 2021

Existing studies identify two major underlying mechanisms behind East and Southeast Asia’s miraculous economic performance in the past 5 decades: accumulation and technological catching-up. This study investigates empirically the relative importance of these two mechanisms in Asian development based on a unified framework. Using canonical cross-economy panel data, the study arrives at three important findings. First, while the process of catching-up through capital accumulation played an important role worldwide, this mechanism was more salient in Asia than in other economies around the globe, especially during the region’s early phase of growth and development. Second, human capital formation had a significant positive effect on the technological catching-up process worldwide. In particular, human capital formation promoted technology adoption more strongly in Asia than in the rest of the world. Third, innovation has also been critical in facilitating recent growth in Asian economies. These results suggest that Asia’s capital-accumulation-driven growth in the early phase induced human capital formation and international technological transfers at later phases, with strong complementarities between these two types of capital. Asian economies likely went through three phases of catching-up, that is, capital accumulation, technological imitation, and then innovation. The experiences of these Asian economies in the last several decades provide critical lessons for latecomer growth and development.
Constructing a Coincident Economic Indicator for India: How Well Does It Track Gross Domestic Product?
Authors: BHADURY SOUMYA , GHOSH SAURABH , KUMAR PANKAJ
Published: September 2021

In India, the first official estimate of quarterly gross domestic product (GDP) is released approximately 7–8 weeks after the end of the reference quarter. To provide an early estimate of current quarter GDP growth, we construct Coincident Economic Indicators for India (CEIIs) using a sequentially expanding list of 6, 9, and 12 high-frequency indicators. These indicators represent various sectors, display high contemporaneous correlation with GDP, and track GDP turning points well. CEII-6 includes domestic economic activity indicators, while CEII-9 incorporates indicators of trade and services and CEII-12 adds financial indicators in the model. We include a financial block in CEII-12 to reflect the growing influence of the financial sector on economic activity. CEIIs are estimated using a dynamic factor model which extracts a common trend underlying the high-frequency indicators. The extracted trend provides a real-time assessment of the state of the economy and helps identify sectors contributing to economic fluctuations. Furthermore, GDP nowcasts using CEIIs show considerable gains in both in-sample and out-of-sample accuracy. In particular, we observe that our GDP growth nowcast closely tracks the recent slowdown in the Indian economy.
A brief review of binary-driven hypernova
Authors: Rueda Jorge A. , Ruffini Remo , Moradi Rahim , Wang Yu
Published: September 2021

Binary-driven hypernova (BdHN) models long gamma-ray burst (GRB) as occurring in the binary systems involving a carbon–oxygen core (CO[Formula: see text]) and a companion neutron star (NS) or a black hole (BH). This model, first proposed in 2012, succeeds and improves upon the fireshell model and the induced gravitational collapse (IGC) paradigm. After nearly a decade of development, the BdHN model has reached a nearly complete structure, giving explanation to all the observables of long bursts into its theoretical framework, and has given a refined classification of long GRB according to the original properties of the progenitors. In this paper, we present a summary of the BdHN model and the physical processes at work in each of the envisaged Episodes during its occurrence and lifetime, duly contextualized in the framework of GRB observations.
Noncanonical scalar fields and the primeval thermal bath
Authors: Lima José Ademir Sales , Almeida Pedro Eleutério Mendonça
Published: September 2021

In this paper, we show that a smooth dynamic evolution from an initial unstable de Sitter stage to the standard radiation phase can analytically be described by a dominant noncanonical scalar field. For all practical purposes, at the end of the vacuum decaying process, the remaining potential energy density is completely stored in the kinetic part of the field satisfying the radiation equation of state. In this model, the early universe is nonsingular, free of horizon and different from many inflationary variants none post-inflationary reheating is required since the formation of the thermal bath is concomitant with inflation. The thermodynamic evolution of the thermal bath is determined. It is also shown that the resulting noncanonical cosmology can be rigorously interpreted as a dynamical [Formula: see text]-model (vacuum fluid) whose spontaneous decaying process into radiation may be the origin of the primeval thermal bath.