bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of elastic thickness non-uniformity on viscoelastic crustal response to magma emplacement: application to the Kutcharo caldera, eastern Hokkaido, Japan
Authors: Yamasaki Tadashi , Takahashi Hiroaki , Ohzono Mako , Wright Tim J , Kobayashi Tomokazu
Published: September 2020

An elastic layer plays an important role in deformation of the crust. At active volcanoes, its thickness would be effectively thinned by a higher geothermal gradient, particularly in a region beneath which magmatic activity is relatively high. This study examines the influence of elastic thickness non-uniformity on viscoelastic crustal deformation by magma emplacement. A 3-D linear Maxwell viscoelastic model is employed, in which an elastic layer underlain by a viscoelastic layer with a spatially uniform viscosity is thinned to be hi in the volcano centre, compared with hi + Δh in the peripheral regions, and a sill-like magma emplacement occurs in the upper layer beneath the centre. It is found that the post-emplacement viscoelastic subsidence is diminished or enhanced by the elastic thickness non-uniformity, depending on whether or not the horizontal width of the magma emplacement (ωs) is greater than the horizontal width (ωe) over which the elastic layer is thinner. The available signature of the non-uniformity is explored by comparison with a model that has a spatially uniform elastic thickness (UET) of hi. If an apparent viscosity (ηa) of the UET model is adjusted so that the difference in post-emplacement subsidence is minimized at the deformation centre, the non-uniformity appears in the overall deformation field as a displacement anomaly over the perimeter of the sill in which viscoelastic subsidence is greater for the non-uniform model. The anomaly is, however, by no more than the magnitude of ∼15 per cent of the maximal syn-emplacement uplift, though ηa is necessarily modified to be ∼0.2–10 times the non-uniform model viscosity (ηc). If ωe is larger than a few times ωs, a weak signature is no longer expected in the deformation field, and ηa is not significantly deviated from ηc. Since the signature appears so faintly in a displacement field, the InSAR data in the Kutcharo caldera for a period from 1993 August 13 to 1998 June 9 do not allow us to capture the non-uniformity. However, it can be concluded that if ωe beneath the caldera is comparable with or greater than the topographic caldera diameter (ωc) as implied by the spatial variation of the geothermal gradient, the non-uniformity has no significant influence. Otherwise, if ωe < ωc, the non-uniformity influences the estimation of the crustal viscosity, but does not affect the overall deformation field. The elastic thickness non-uniformity can be theoretically captured in the deformation field, but in practice, its influence, particularly on estimating crustal viscosity, cannot be properly inferred without other geophysical data such as the geothermal gradient in and around the caldera.
Participant engagement in a community based participatory research study to reduce alcohol use among Latino immigrant men
Authors: Torres Vanessa N , Williams Emily C , Ceballos Rachel M , Donovan Dennis M , Duran Bonnie , Ornelas India J
Published: September 2020

Although Latino immigrant men experience many health disparities, they are underrepresented in research to understand and address disparities. Community Based Participatory Research (CBPR) has been identified to encourage participant engagement and increase representation in health disparities research. The CBPR conceptual model describes how partnership processes and study design impact participant engagement in research. Using this model, we sought to describe how these domains influenced participant engagement in a pilot randomized controlled trial of brief intervention for unhealthy alcohol use (n = 121) among Latino immigrant men. We conducted interviews with a sample of study participants (n = 25) and reviewed logs maintained by ‘promotores’. We identified facilitators of participant engagement, including the relevance of the study topic, alignment with participants’ goals to improve their lives, partnerships with study staff that treated participants respectfully and offered access to resources. Further, men reported that the study time and location were convenient and that they appreciated being compensated for their time. Barriers to participant engagement included survey questions that were difficult to understand and competing demands of work responsibilities. Findings suggest that engaging underserved communities requires culturally responsive and community engagement strategies that promote trust. Future studies should further investigate how CBPR partnership processes can inform intervention research.
Clinical-stage Approaches for Imaging Chronic Inflammation and Fibrosis in Crohn’s Disease
Authors: Greer Mary-Louise C , Cytter-Kuint Ruth , Pratt Li-tal , Soboleski Don , Focht Gili , Castro Denise A
Published: September 2020

The number of imaging-based indices developed for inflammatory bowel disease as research tools, objectively measuring ileocolonic and perianal activity and treatment response, has expanded in the past 2 decades. Created primarily to assess Crohn’s disease (CD), there is increasing adoption of these indices into the clinical realm to guide patient care. This translation has been facilitated by validation in adult and pediatric populations, prompted by simplification of score calculations needed for practical application outside the research environment. The majority of these indices utilize magnetic resonance imaging (MRI), specifically MR enterography (MRE) and pelvic MRI, and more recently ultrasound. This review explores validated indices by modality, anatomic site and indication, including for documentation of the presence and extent of CD, disease progression, complications, and treatment response, highlighting those in clinical use or with the potential to be. As well, it details index imaging features used to quantify chronic inflammatory activity, severity, and to lesser extent fibrosis, in addition to their reference standards and any modifications. Validation in the pediatric population of indices primarily developed in adult cohorts such as the Magnetic Resonance Index of Activity (MaRIA), the Simplified Magnetic Resonance Index of Activity (MARIAs), and the MRE global score (MEGS), together with newly developed pediatric-specific indices, are discussed. Indices that may be predictive of disease course and investigational techniques with the potential to provide future imaging biomarkers, such as multiparametric MRI, are also briefly considered.
Hyperbaric Oxygen Therapy in Chronic Inflammatory Conditions of the Pouch
Authors: Hasan Badar , Yim Yunjoo , Ur Rashid Mamoon , Khalid Rumman A , Sarvepalli Deepika , Castaneda Daniel , Ur Rahman Asad , Palekar Nicole , Charles Roger , Castro Fernando J , Shen Bo
Published: September 2020

Background

Pouchitis can be a chronic complication of ileal pouch-anal anastomosis. We aimed to determine the efficacy and safety of hyperbaric oxygen therapy (HBOT) for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch.

Methods

This was a retrospective case series of adults with inflammatory bowel disease (IBD) who underwent ileal pouch-anal anastomosis and then developed CARP and received HBOT between January 2015 and October 2019. A modified Pouchitis Disease Activity Index (mPDAI) score was used to quantify subjective symptoms (0–6) and endoscopic findings (0–6) before and after HBOT.

Results

A total of 46 patients were included, with 23 (50.0%) being males with a mean age of 43.6 ± 12.9 years. The median number of HBOT sessions was 30 (range 10–60). There was a significant reduction in the mean mPDAI symptom subscore from 3.19 to 1.91 after HBOT (P < 0.05). The pre- and post-HBOT mean mPDAI endoscopy subscores for the afferent limb were 2.31 ± 1.84 and 0.85 ± 1.28 (P = 0.006); for the pouch body, 2.34 ± 1.37 and 1.29 ± 1.38 (P < 0.001); and for the cuff, 1.93 ± 1.11 and 0.63 ± 1.12 (P < 0.001), respectively. Transient side effects included ear barotrauma in 5 patients (10.9%) and hyperbaric myopic vision changes in 5 patients (10.9%).

Conclusions

Despite minor adverse events, HBOT was well tolerated in patients with CARP and significantly improved symptoms and endoscopic parameters.
Wavelet-based approximations of pointwise bound constraints in Lebesgue and Sobolev spaces
Authors: Dahlke S , Surowiec T M
Published: September 2020

Many problems in optimal control, PDE-constrained optimization and constrained variational problems include pointwise bound constraints on the feasible controls and state variables. Most well-known approaches for treating such pointwise inequality constraints in numerical methods rely on finite element discretizations and interpolation arguments. We propose an alternative means of discretizing pointwise bound constraints using a wavelet-based discretization. The main results show that the discrete, approximating sets converge in the sense of Mosco to the original sets. In situations of higher regularity, convergence rates follow immediately from the underlying wavelet theory. The approach exploits the fact that one can easily transform between a given multiscale wavelet representation and single-scale representation with linear complexity. This allows, for example, a direct treatment of variational problems involving fractional operators, without the need for lifting techniques. We demonstrate this fact with several numerical examples of fractional obstacle problems.
Restoring Legitimacy: Public Diplomacy Campaigns during Civil Wars
Authors: Mattiacci Eleonora , Jones Benjamin T
Published: September 2020

Governments involved in civil wars often gain a strategic advantage from intentionally killing civilians. However, targeting civilians might also tarnish perceptions of the government’s legitimacy abroad, increasing the risk of foreign actors punishing the government. How can governments attempt to navigate this dilemma? Focusing on the United States as one of the most frequent interveners in civil wars after the Cold War, we examine one particular strategy governments might employ: public diplomacy campaigns (PDCs) targeting both the public and elites in the United States. PDCs can help governments restore perceptions of their legitimacy abroad in the face of civilian targeting by mobilizing coalitions of support and undermining critics. When governments can achieve plausible deniability for civilian deaths via militias, PDCs enable governments to reduce the damage to foreign perceptions of their legitimacy. When rebels engage in civilian targeting, PDCs allow governments to publicize these actions. We compile data PDCs in the United States by governments engaged in civil wars. Our results have important implications for current understandings of civil war combatant foreign policies, foreign interventions, and international human rights laws and norms.
The Testament politique of Nicholas I? Monarchical propaganda and the birth of a national collection
Authors: Sopo Elina
Published: September 2020

This article explores the symbolic function of ritual and collecting during the political rule of Tsar Nichol- as I through a close reading of the unpublished letters of the protégés of the emperor who played decisive roles in the Society for the Encouragement of the Culture of the Fine Arts in Finland. It explores how long-established aspects of the psychology of authority and monarchical propaganda were performed and expressed, and how they were deployed in the image creation and governance of the empire. Also addressed are questions about the degree to which the government’s view of Romantic nationalism was ambivalent, and how the essentially ancien régime outlook of an enlightened autocrat came to be reconciled with the radical views of the nationalists.
Microsatellites for the Neotropical Ant, Odontomachus chelifer (Hymenoptera: Formicidae)
Authors: Lemos Alessandra S M , Azevedo-Silva Marianne , Gonçalves-Neto Salatiel , Souza Anete P , Oliveira Paulo S
Published: September 2020

Odontomachus chelifer (Latreille) (Ponerinae) is a ground-dwelling, predominantly carnivorous ant whose colonies may contain multiple egg-laying queens and are potentially susceptible to border effects in the Brazilian savanna known as Cerrado. The ecology and natural history of O. chelifer is well studied, but very little is known about the genetic diversity of O. chelifer colonies. In this study, we developed microsatellite markers for the study of genetic variation in O. chelifer. We created a microsatellite-enriched library that resulted in the development and characterization of 22 markers, of which 18 were found to be polymorphic in the population studied. The mean expected heterozygosity was 0.59, whereas the mean rarified allelic richness was determined as 4.27 alleles per locus. The polymorphism level detected was similar to genetic diversity estimates found in other poneromorph ant species. The microsatellites developed here are likely to be useful for the investigation of colony structure, functional polygyny, breeding system, and population genetics in O. chelifer. Moreover, the description of O. chelifer’s genetic diversity is crucial for its conservation and maintenance of its ecological role in the Cerrado savanna.
Genetic diversity and conservation of the endemic tuco-tucoCtenomys ibicuiensis(Rodentia: Ctenomyidae)
Authors: Medeiros Mayara Delagnelo , Galiano Daniel , Kubiak Bruno Busnello , Roratto Paula Angélica , de Freitas Thales Renato Ochotorena
Published: September 2020

Endemic, small range species are susceptible to environmental changes and landscape modification. Understanding genetic diversity and distributional patterns is important for implementation of effective conservation measures. In this context, genetic diversity was evaluated to update the conservation status of an endemic tuco-tuco, Ctenomys ibicuiensis. Phylogeographic and population genetic analyses of mitochondrial DNA and microsatellite loci were carried out using 46 individuals sampled across the species’ distribution. Ctenomys ibicuiensis presented moderate to high genetic diversity and highly structured populations with low levels of gene flow and isolation by distance. Anthropogenic landscape changes threaten this restricted-range tuco-tuco. Considering its limited geographic distribution and highly structured populations with low gene flow, we consider C. ibicuiensis to be at significant risk of extinction.
Military Innovation and Technological Determinism: British and US Ways of Carrier Warfare, 1919–1945
Authors: Kuo Kendrick
Published: September 2020

Major theories of military innovation suggest that military organizations will converge on the proper employment of new weapons if they are responsive to strategic threats and overcome cultural, bureaucratic, and material constraints. Using a comparison of British and US interwar carrier programs, I show how these standard intuitions about military innovation wrongly assume that there is a predetermined performance trajectory embedded in new technology. The Royal Navy employed carrier technology differently from its American counterpart, not because of cultural biases, bureaucratic parochialism, or resource scarcity, but because the British possessed in-theater military bases and faced the threat of land-based enemy aircraft in the North Sea, the Mediterranean, and the Far East. British carrier warfare, which the field of military innovation studies roundly criticizes as non-innovative and ineffective, was in fact a creative solution for Britain's geostrategic challenges that proved effective for the first couple of years of World War II. Since carrier warfare is a canonical case for military innovation studies, revising our understanding of Britain's interwar carrier program has significant implications for the way scholars conceptualize military innovation and its relationship to wartime military performance.
Between contestation and collaboration: The internal dynamics of multidisciplinary accounting firm responses to institutional pressures
Authors: Taminiau Yvette , Heusinkveld Stefan
Published: September 2020

The colonization of adjacent professional fields has been considered as crucial to understand the success and influence of large accounting firms, such as the Big 4. Yet, given the complexities of managing different professional groups, remarkably little is known about the internal dynamics behind large multidisciplinary accounting firms’ external responses to institutional pressures. In this article, we show how exogenous coercive pressure, such as regulation (in this case Dutch accountancy regulations), not only affect the day-to-day work of accountants, but also that of non-accountants such as tax advisors. From the perception of the tax advisors who confront regulations which are not ‘theirs’, we show how their internal responses evolve and tread a fine line between contestation and collaboration with their colleague accountants/auditors. Using a boundary work perspective, we examine this shift in responses and explain how tensions between professional groups may be reduced. Overall, our study not only furthers our insights into the internal dynamics behind professional service firms’ external responses, but also sheds light on why professional groups stay on board despite unfavorable internal conditions.
Neural-network assisted study of nitrogen atom dynamics on amorphous solid water – I. adsorption and desorption
Authors: Molpeceres Germán , Zaverkin Viktor , Kästner Johannes
Published: September 2020

Dynamics of adsorption and desorption of (4S)-N on amorphous solid water are analysed using molecular dynamic simulations. The underlying potential energy surface was provided by machine-learned interatomic potentials. Binding energies confirm the latest available theoretical and experimental results. The nitrogen sticking coefficient is close to unity at dust temperatures of 10 K but decreases at higher temperatures. We estimate a desorption time-scale of 1 μs at 28 K. The estimated time-scale allows chemical processes mediated by diffusion to happen before desorption, even at higher temperatures. We found that the energy dissipation process after a sticking event happens on the picosecond time-scale at dust temperatures of 10 K, even for high energies of the incoming adsorbate. Our approach allows the simulation of large systems for reasonable time-scales at an affordable computational cost and ab initio accuracy. Moreover, it is generally applicable for the study of adsorption dynamics of interstellar radicals on dust surfaces.
Sex-Specific Selection Drives the Evolution of Alternative Splicing in Birds
Authors: Rogers Thea F , Palmer Daniela H , Wright Alison E
Published: September 2020

Males and females of the same species share the majority of their genomes, yet they are frequently exposed to conflicting selection pressures. Gene regulation is widely assumed to resolve these conflicting sex-specific selection pressures, and although there has been considerable focus on elucidating the role of gene expression level in sex-specific adaptation, other regulatory mechanisms have been overlooked. Alternative splicing enables different transcripts to be generated from the same gene, meaning that exons which have sex-specific beneficial effects can in theory be retained in the gene product, whereas exons with detrimental effects can be skipped. However, at present, little is known about how sex-specific selection acts on broad patterns of alternative splicing. Here, we investigate alternative splicing across males and females of multiple bird species. We identify hundreds of genes that have sex-specific patterns of splicing and establish that sex differences in splicing are correlated with phenotypic sex differences. Additionally, we find that alternatively spliced genes have evolved rapidly as a result of sex-specific selection and suggest that sex differences in splicing offer another route to sex-specific adaptation when gene expression level changes are limited by functional constraints. Overall, our results shed light on how a diverse transcriptional framework can give rise to the evolution of phenotypic sexual dimorphism.
Sex-specific epigenetic profile of inner cell mass of mice conceived in vivo or by IVF
Authors: Ruggeri Elena , Lira-Albarrán Saúl , Grow Edward J , Liu Xiaowei , Harner Royce , Maltepe Emin , Ramalho-Santos Miguel , Donjacour Annemarie , Rinaudo Paolo
Published: September 2020

The preimplantation stage of development is exquisitely sensitive to environmental stresses, and changes occurring during this developmental phase may have long-term health effects. Animal studies indicate that IVF offspring display metabolic alterations, including hypertension, glucose intolerance and cardiac hypertrophy, often in a sexual dimorphic fashion. The detailed nature of epigenetic changes following in-vitro culture is, however, unknown. This study was performed to evaluate the epigenetic (using whole-genome bisulfite sequencing (WGBS) and assay for transposase-accessible chromatin using sequencing (ATAC-seq)) and transcriptomic changes (using RNA-seq) occurring in the inner cell mass (ICM) of male or female mouse embryos generated in vivo or by IVF. We found that the ICM of IVF embryos, compared to the in-vivo ICM, differed in 3% of differentially methylated regions (DMRs), of which 0.1% were located on CpG islands. ATAC-seq revealed that 293 regions were more accessible and 101 were less accessible in IVF embryos, while RNA-seq revealed that 21 genes were differentially regulated in IVF embryos. Functional enrichment analysis revealed that stress signalling (STAT and NF-kB signalling), developmental processes and cardiac hypertrophy signalling showed consistent changes in WGBS and ATAC-seq platforms. In contrast, male and female embryos showed minimal changes. Male ICM had an increased number of significantly hyper-methylated DMRs, while only 27 regions showed different chromatin accessibility and only one gene was differentially expressed. In summary, this study provides the first comprehensive analysis of DNA methylation, chromatin accessibility and RNA expression changes induced by IVF in male and female ICMs. This dataset can be of value to all researchers interested in the developmental origin of health and disease (DOHaD) hypothesis and might lead to a better understanding of how early embryonic manipulation may affect adult health.
SilencerDB: a comprehensive database of silencers
Authors: Zeng Wanwen , Chen Shengquan , Cui Xuejian , Chen Xiaoyang , Gao Zijing , Jiang Rui
Published: September 2020

Gene regulatory elements, including promoters, enhancers, silencers, etc., control transcriptional programs in a spatiotemporal manner. Though these elements are known to be able to induce either positive or negative transcriptional control, the community has been mostly studying enhancers which amplify transcription initiation, with less emphasis given to silencers which repress gene expression. To facilitate the study of silencers and the investigation of their potential roles in transcriptional control, we developed SilencerDB (http://health.tsinghua.edu.cn/silencerdb/), a comprehensive database of silencers by manually curating silencers from 2300 published articles. The current version, SilencerDB 1.0, contains (1) 33 060 validated silencers from experimental methods, and (ii) 5 045 547 predicted silencers from state-of-the-art machine learning methods. The functionality of SilencerDB includes (a) standardized categorization of silencers in a tree-structured class hierarchy based on species, organ, tissue and cell line and (b) comprehensive annotations of silencers with the nearest gene and potential regulatory genes. SilencerDB, to the best of our knowledge, is the first comprehensive database at this scale dedicated to silencers, with reliable annotations and user-friendly interactive database features. We believe this database has the potential to enable advanced understanding of silencers in regulatory mechanisms and to empower researchers to devise diverse applications of silencers in disease development.
Survival, Dependency, and Health-Related Quality of Life in Patients With Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial
Authors: Hua Xinyang , Gray Alastair , Wolstenholme Jane , Clarke Philip , Molyneux Andrew J , Kerr Richard S C , Clarke Alison , Sneade Mary , Rivero-Arias Oliver
Published: September 2020

BACKGROUND

Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on clinical outcomes after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling.

OBJECTIVE

To evaluate the long-term quality-adjusted life years (QALYs) gained of endovascular coiling compare to neurosurgical clipping in the UK cohort of ISAT.

METHODS

Between September 12, 1994 and May 1, 2002, patients with ruptured intracranial aneurysms who were assumed treatment equipoise were randomly allocated to either neurosurgical clipping or endovascular coiling. We followed-up 1644 patients in 22 UK neurosurgical centers for a minimum of 10 yr. Health-related quality of life (HRQoL) was collected through yearly questionnaires, measured by utilities calculated from the EQ-5D-3L. We compared HRQoL between the 2 treatment groups over a period of 10 yr. In all, 1-yr, 5-yr, and 10-yr QALYs were estimated by combining utility and survival information.

RESULTS

Higher average utility values were found in the endovascular group throughout the follow-up period, with mean differences between groups statistically significant in most years. The 10-yr QALYs were estimated to be 6.68 (95% CI: 6.45-6.90) in the coiling group and 6.32 (95% CI: 6.10-6.55) in the clipping group, respectively, a significant mean difference of 0.36 (95% CI: 0.04-0.66). A third of this mean QALYs gain was estimated to derive solely from HRQoL differences.

CONCLUSION

HRQoL after treatment of a ruptured intracranial aneurysm was better after endovascular coiling compared to neurosurgical clipping, which contributed significantly to the QALYs gained over a 10-yr period.
A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes
Authors: Hanson Derek , Hoffman Lindsey M , Nagabushan Sumanth , Goumnerova Liliana C , Rathmann Allison , Vogel Timothy , Ziegler David S , Chi Susan
Published: September 2020

Background

Embryonal tumor with multilayer rosettes (ETMR) is a rare CNS malignancy affecting young children that carries a very poor prognosis. Treatment with intensive surgical resection, radiotherapy, and high-dose chemotherapy is insufficient treatment in the vast majority of cases. Effective, biologically based therapies for this tumor are therefore desperately needed. The Dana-Farber Cancer Institute–modified IRS-III protocol incorporates preclinically active agents, such as doxorubicin and actinomycin D, into the treatment regimen for ETMR and may improve patient outcomes.

Methods

The authors present a case series of 5 children with ETMR treated with an IRS-III-based chemotherapy backbone.

Results

All 5 patients received a gross-total tumor resection. Patients received between 12 and 51 weeks of IRS-III therapy at the discretion of their treating physician. Four patients received focal radiation therapy, with the fifth patient instead receiving a cycle of high-dose chemotherapy with autologous stem cell rescue. Four patients have progression-free survival of more than 18 months. Chemotherapy treatment was reasonably tolerated by all 5 patients with one case of mild sinusoidal obstructive syndrome and one case of Grade 3 peripheral neuropathy.

Conclusions

The patient outcomes in this small cohort are far better than would be expected based on the historical survival for this tumor. Given the tremendous need for effective therapy for ETMR, further investigation of this approach is warranted. An international consensus protocol based on the IRS-III regimen has been developed and will be available through a multicenter clinical trial and a global treatment registry.
Adjusting for protein quality by food source may affect nutrient density metrics
Authors: Drewnowski Adam
Published: September 2020

Methods to assess nutrient density of foods, commonly known as nutrient profiling (NP), typically include protein as a component. In this study, the goal was to apply a correction for protein quality by food source to selected NP algorithms. Analyses of 378 component foods of the Fred Hutch food frequency questionnaire showed that animal-source foods (ie, meat, eggs, and dairy) along with some soy products and nuts were the only foods that provided > 20% of the daily value (DV) of protein per 100 g or per 100 kcal. Most beans, pulses, legumes, grains, and vegetables provided <10% DV of protein per 100 g or per 100 kcal. Adjusting for protein quality using a simplified Protein Digestibility Corrected Amino Acid Score (PDCAAS) had consequences for point-based NP models (namely, Nutri-Score) and for continuous nutrient density scores (namely, Nutrient Rich Foods). Quantitative methods that use protein content to capture nutrient density may require a protein-quality adjustment, especially when adapted for use in low- and middle-income countries where protein quality is an issue of public health concern.
Financial, Food, and Housing Insecurity Due to Coronavirus Disease 2019 Among At-Risk People With Human Immunodeficiency Virus in a Nonurban Ryan White HIV/AIDS Program Clinic
Authors: Sherbuk Jacqueline E , Williams Brooke , McManus Kathleen A , Dillingham Rebecca
Published: September 2020

Coronavirus disease 2019 negatively impacts social determinants of health that contribute to disparities for people with human immunodeficiency virus (HIV). Insecurity of food, housing, and employment increased significantly in April 2020 among patients with lower incomes at a Ryan White HIV/AIDS program clinic in the Southern United States.
Science rules! A qualitative study of scientists’ approaches to grant lottery
Authors: Philipps Axel
Published: September 2020

Using peer review to assess the validity of research proposals has always had its fair share of critics, including a more-than-fair-share of scholars. The debate about this method of assessing these proposals now seems trivial when compared with assessing the validity for granting funding by lottery. Some of the same scholars have suggested that the way grant lottery was being assessed has made random allocation seem even-handed, less biased and more supportive of innovative research. But we know little of what researchers actually think about grant lottery and even less about the thoughts of those scientists who rely on funding. This paper examines scientists’ perspectives on selecting grants by ‘lots’ and how they justify their support or opposition. How do they approach something scientifically that is, in itself, not scientific? These approaches were investigated with problem-centered interviews conducted with natural scientists in Germany. The qualitative interviews for this paper reveal that scientists in dominated and dominating field positions are, more or less, open to the idea of giving a selection process by lots a try. Nonetheless, they are against pure randomization because from their point of view it is incompatible with scientific principles. They rather favor a combination of grant lottery and peer review processes, assuming that only under these conditions could randomly allocated funding be an integral and legitimate part of science.
Adverse effects related to methotrexate polyglutamate levels: adjudicated results from the cardiovascular inflammation reduction trial
Authors: Xu Chang , Selhub Jacob , Jacques Paul , Paynter Nina P , MacFadyen Jean G , Glynn Robert J , Ridker Paul M , Solomon Daniel H
Published: September 2020

Objectives

Methotrexate is widely used at low dosages (LD-MTX) for non-oncologic indications and is associated with a variety of adverse effects (AEs). We sought to determine whether concentrations of the active metabolite, MTX polyglutamates (MTX-PGs) 1–5, correlate with AEs.

Method

We examined data from the LD-MTX arm of the randomized double-blind Cardiovascular Inflammation Reduction Trial (CIRT). All AEs were blindly adjudicated and monitoring laboratories were tested centrally. The MTX-PGs 1–5 were assessed in one reference laboratory using liquid chromatography–tandem mass spectrometry. Based on prior literature, MTX-PGs 3–5 were chosen as the exposure of interest and quartiles of MTX-PGs 3–5 were assessed for their relationship with all AEs and each pre-specified category of AE using adjusted Cox proportional hazards regression.

Results

Of the 2391 subjects randomized to LD-MTX, MTX-PG levels were available for 1319 subjects (median dosage 16.1 mg/week) from the 8 month visit. We followed these subjects for a median of 2.2 years [interquartile range (IQR) 1.5–2.9]. Higher MTX-PG3–5 levels were related to an increased risk of anaemia [compared with quartile 1 (Q1); hazard ratio (HR) for Q4 1.27 (95% CI 0.98, 1.65), P for trend = 0.05] and a decreased risk of thrombocytopenia [HR for Q4 0.52 (95% CI 0.32, 0.84), P for trend = 0.05]. MTX-PG3–5 levels >134 nmol/l were associated with an increased risk of liver abnormalities [HR 1.36 (95% CI 1.08, 1.72)].

Conclusions

Higher MTX- PG3–5 levels were modestly associated with LD-MTX AEs, including anaemia and liver function abnormalities, but a reduced risk of thrombocytopenia and haemorrhage.

Clinical trial registration

NCT 01594333.
Identification of White Matter Networks Engaged in Object (Face) Recognition Showing Differential Responses to Modulated Stimulus Strength
Authors: Li Muwei , Ding Zhaohua , Gore John C
Published: September 2020

Blood-oxygenation-level-dependent (BOLD) signals in magnetic resonance imaging indirectly reflect neural activity in cortex, but they are also detectable in white matter (WM). BOLD signals in WM exhibit strong correlations with those in gray matter (GM) in a resting state, but their interpretation and relationship to GM activity in a task are unclear. We performed a parametric visual object recognition task designed to modulate the BOLD signal response in GM regions engaged in higher order visual processing, and measured corresponding changes in specific WM tracts. Human faces embedded in different levels of random noise have previously been shown to produce graded changes in BOLD activation in for example, the fusiform gyrus, as well as in electrophysiological (N170) evoked potentials. The magnitudes of BOLD responses in both GM regions and selected WM tracts varied monotonically with the stimulus strength (noise level). In addition, the magnitudes and temporal profiles of signals in GM and WM regions involved in the task coupled strongly across different task parameters. These findings reveal the network of WM tracts engaged in object (face) recognition and confirm that WM BOLD signals may be directly affected by neural activity in GM regions to which they connect.
Determinants of dengue virus dispersal in the Americas
Authors: Allicock Orchid M , Sahadeo Nikita , Lemey Philippe , Auguste Albert J , Suchard Marc A , Rambaut Andrew , Carrington Christine V F
Published: September 2020

Dengue viruses (DENVs) are classified into four serotypes, each of which contains multiple genotypes. DENV genotypes introduced into the Americas over the past five decades have exhibited different rates and patterns of spatial dispersal. In order to understand factors underlying these patterns, we utilized a statistical framework that allows for the integration of ecological, socioeconomic, and air transport mobility data as predictors of viral diffusion while inferring the phylogeographic history. Predictors describing spatial diffusion based on several covariates were compared using a generalized linear model approach, where the support for each scenario and its contribution is estimated simultaneously from the data set. Although different predictors were identified for different serotypes, our analysis suggests that overall diffusion of DENV-1, -2, and -3 in the Americas was associated with airline traffic. The other significant predictors included human population size, the geographical distance between countries and between urban centers and the density of people living in urban environments.
Evaluating the effectiveness of the PA Foundation's Mental Health Outreach fellowship
Authors: Forbes Jennifer , Pierce Caroline , Sappe-Watkins Lynette
Published: September 2020

Objectives:

Mental Health First Aid (MHFA) is designed to help the general public acquire the knowledge and skills needed to respond to a person in a mental health emergency and offer support to someone in emotional distress. Through the PA Foundation's Mental Health Outreach Fellowship, 16 physician assistants (PAs) were selected to become MHFA instructors and teach the course to members of their local communities over 1 year.

Methods:

MHFA course evaluations, completed by course participants, were reviewed to determine the effectiveness of the PA fellows as instructors.

Results:

The fellows' mean evaluation instructor presentation score was 4.82 and the mean course content score was 4.75. The national mean for instructor presentation was 4.72 for presentation and 4.66 for course content. The maximum possible score in each category was a 5.

Conclusions:

The PAs selected for the Mental Health Outreach Fellowship were effective MHFA instructors. Benefits to having a PA serve as the instructor include positively affecting communities by increasing the public's mental health literacy, reducing the stigma associated with mental illness, increasing visibility and promotion of the PA profession, and enhancement of a PA's individual career through education and service.
Impact of Skin Suture Pattern on Incision Perfusion Using Intraoperative Laser Angiography: A Randomized Clinical Trial of Patients With Ankle Fractures
Authors: Shorten Peter , Haimes Mark , Nesbit Robert , Bartlett Craig , Schottel Patrick
Published: September 2020

Objectives:

To assess which skin suture pattern—simple, vertical mattress, horizontal mattress, Allgöwer–Donati (AD), or running subcuticular—enables the greatest degree of perfusion as measured by indocyanine green laser angiography after ankle fracture surgery.

Design:

Prospective, randomized.

Setting:

Level 1 Academic Trauma Center.

Patients/Participants:

Seventy-five patients undergoing ankle fracture surgery were prospectively randomized to 1 of 5 skin suture patterns (n = 15 per cohort). Patient demographics and operative parameters were similar between groups.

Main Outcome Measurements:

Skin perfusion was assessed intraoperatively after skin closure using indocyanine green laser angiography and quantified in fluorescence units. Two perfusion values were collected: (1) mean incision perfusion was the mean of 10 points along the incision and (2) mean perfusion impairment was the perfusion difference between the incision and the skin adjacent to it. We also collected a postoperative patient scar assessment score.

Results:

Running subcuticular closure had significantly better mean incision perfusion than all other closure patterns. Mean perfusion impairment also favored running subcuticular closure, which was significantly lower than all other suture patterns except AD. We found no patient perceived cosmetic differences between the 5 suture pattern types.

Conclusions:

Running subcuticular suture pattern resulted in the greatest incision perfusion than simple, horizontal mattress, vertical mattress, and AD techniques after ankle fracture fixation.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Fate of the Uninsured Ankle Fracture: Significant Delays in Treatment Result in an Increased Risk of Surgical Site Infection
Authors: Zelle Boris A. , Johnson Taylor R. , Ryan James C. , Martin Case W. , Cabot John H. , Griffin Leah P. , Bullock Travis S. , Ahmad Farhan , Brady Christina I. , Shah Kush
Published: September 2020

Objective:

To examine the impact of insurance status on access to orthopaedic care and incidence of surgical site complications in patients with closed unstable ankle fractures.

Design:

Retrospective chart review.

Setting:

Certified Level-1 urban trauma center and county facility.

Participants:

Four hundred eighty-nine patients with closed unstable ankle fractures undergoing open reduction and internal fixation between 2014 and 2016.

Intervention:

Open reduction and internal fixation of unstable ankle fracture.

Main Outcome Measures:

Time from injury to presentation, time from injury to surgery, rate of surgical site infections, and loss to follow-up.

Results:

A total of 489 patients (70.5% uninsured vs. 29.5% insured) were enrolled. Uninsured patients were more likely to be present to an outside hospital first (P = 0.004). Time from injury to presentation at our hospital was significantly longer in uninsured patients (4.5 ± 7.6 days vs. 2.3 ± 5.5 days, P < 0.001). Time from injury to surgery was significantly longer in uninsured patient (9.4 ± 8.5 days vs. 7.3 ± 9.1 days, P < 0.001). Uninsured patients were more likely to be lost to postoperative follow-up care (P = 0.002). A logistic regression analysis demonstrated that delayed surgical timing was directly associated with an increased risk of postoperative surgical site infection (P = 0.002).

Conclusions:

Uninsured patients with ankle fractures requiring surgery experience significant barriers regarding access to health care. Delay of surgical management significantly increases the risk of surgical site infections in closed unstable ankle fractures.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Inpatient Mortality According to Level of Respiratory Support Received for Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019) Infection: A Prospective Multicenter Study
Authors: Palazzuoli Alberto , Ruberto Franco , De Ferrari Gaetano M. , Forleo Giovanni , Secco Gioel G. , Ruocco Gaetano M. , D’Ascenzo Fabrizio , Mojoli Francesco , Monticone Silvia , Paggi Anita , Vicenzi Marco , Corcione Silvia , Palazzo Anna G. , Landolina Maurizio , Taravelli Erika , Tavazzi Guido , Blasi Francesco , Mancone Massimo , Birtolo Lucia I. , Alessandri Francesco , Infusino Fabio , Pugliese Francesco , Fedele Francesco , De Rosa Francesco Giuseppe , Emmett Michael , Schussler Jeffrey M. , McCullough Peter A. , Tecson Kristen M.
Published: September 2020

Objectives:

To describe patients according to the maximum degree of respiratory support received and report their inpatient mortality due to coronavirus disease 2019.

Design:

Analysis of patients in the Coracle registry from February 22, 2020, to April 1, 2020.

Setting:

Hospitals in the Piedmont, Lombardy, Tuscany, and Lazio regions of Italy.

Patients:

Nine-hundred forty-eight patients hospitalized for coronavirus disease 2019.

Interventions:

None.

Measurements and Main Results:

Among 948 patients, 122 (12.87%) received invasive ventilation, 637 (67.19%) received supplemental oxygen only, and 189 (19.94%) received no respiratory support. The median (quartile 1–quartile 3) age was 65 years (54–76.59 yr), and there was evidence of differential respiratory treatment by decade of life (p = 0.0046); patients greater than 80 years old were generally not intubated. There were 606 men (63.9%) in this study, and they were more likely to receive respiratory support than women (p < 0.0001). The rate of in-hospital death for invasive ventilation recipients was 22.95%, 12.87% for supplemental oxygen recipients, and 7.41% for those who received neither (p = 0.0004). A sensitivity analysis of the 770 patients less than 80 years old revealed a lower, but similar mortality trend (18.02%, 8.10%, 5.23%; p = 0.0008) among the 14.42%, 65.71%, and 19.87% of patients treated with mechanical ventilation, supplemental oxygen only, or neither. Overall, invasive ventilation recipients who died were significantly older than those who survived (median age: 68.5 yr [60–81.36 yr] vs 62.5 yr [55.52–71 yr]; p = 0.0145).

Conclusions:

Among patients hospitalized for coronavirus disease 2019, 13% received mechanical ventilation, which was associated with a mortality rate of 23%.
Graph Convolutional Networks-Based Noisy Data Imputation in Electronic Health Record
Authors: Lee Byeong Tak , Kwon O-Yeon , Park Hyunho , Cho Kyung-Jae , Kwon Joon-Myoung , Lee Yeha
Published: September 2020

Objectives:

A deep learning-based early warning system is proposed to predict sepsis prior to its onset.

Design:

A novel algorithm was devised to detect sepsis 6 hours prior to its onset based on electronic medical records.

Setting:

Retrospective cohorts from three separate hospitals are used in this study. Sepsis onset was defined based on Sepsis-3. Algorithms are evaluated based on the score function used in the Physionet Challenge 2019.Patients: Over 60,000 ICU patients with 40 clinical variables (vital signs, laboratory results) for each hour of a patient’s ICU stay were used.

Interventions:

None.

Measurements and Main Results:

The proposed algorithm predicted the onset of sepsis in the preceding n hours (where n = 4, 6, 8, or 12). Furthermore, the proposed method compared how many sepsis patients can be predicted in a short time with other methods. To interpret a given result in a clinical perspective, the relationship between input variables and the probability of the proposed method were presented. The proposed method achieved superior results (area under the receiver operating characteristic curve, area under the precision-recall curve, and score) and predicted more sepsis patients in advance. In official phase, the proposed method showed the utility score of –0.101, area under the receiver operating characteristic curve 0.782, area under the precision-recall curve 0.041, accuracy 0.786, and F-measure 0.046.

Conclusions:

Using Physionet Challenge 2019, the proposed method can accurately and early predict the onset of sepsis. The proposed method can be a practical early warning system in the environment of real hospitals.
Myocardial Infarction With Nonobstructive Coronary Arteries
Authors: Polyak Alexander , Frishman William
Published: September 2020

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is the current term used to describe patients who have a myocardial infarction but have normal, non-obstructed coronary arteries on a coronary angiogram. There is still much debate over the definition, diagnosis, management and treatment of MINOCA. However, MINOCA is not a benign condition; prompt recognition and diagnosis can lead to better management and treatment and thus improve patient outcomes. This review article will update the most recent definition of MINOCA, discuss epidemiology and etiology, and review the diagnostic workup and management options for patients presenting with signs and symptoms of MINOCA.