bluuebunny/crossref_metadata_2025 huggingface dataset:
Are cytochrome P4502D6 and apolipoprotein E genotypes associated with long‐term cognitive and functional changes in patients treated with donepezil?
Authors: Pamio Maria V. , Trevisan Caterina , Pigozzo Sabrina , De Rui Marina , Devita Maria , Girardi Agostino , Manzato Enzo , Sergi Giuseppe , Coin Alessandra
Published: April 2020

Aim

We investigated the associations of the single‐nucleotide polymorphism rs1080985 of cytochrome P4502D6 (CYP2D6) and the apolipoprotein E (APOE) genotypes with cognitive and functional changes in patients treated with donepezil.

Methods

Sixty‐five outpatients with Alzheimer's disease or mixed dementia being treated with donepezil were assessed at baseline and over 27 months. Changes in cognitive status, assessed with the Mini‐Mental State Examination, and in functional status, assessed by the Activities of Daily Living Scale and the Instrumental Activities of Daily Living Scale, were evaluated as a function of CYP2D6 and APOE genotypes by using linear mixed models. Multiplicative interactions between the CYP2D6 and APOE genotypes and time were investigated.

Results

Individuals with the mutated CYP2D6 exhibited a slower decline in total Mini‐Mental State Examination scores, orientation, registration, and functional status than those with the wild type. A significant interaction between CYP2D6, APOE, and time was found for changes in the Activities of Daily Living Scale; among the ε4 carriers, those with the mutated CYP2D6 exhibited a slower decline on the Activities of Daily Living Scale than those with the wild type.

Conclusion

The CYP2D6 and APOE genotypes may modulate the effectiveness of donepezil on cognitive and functional status.
A comparative review of intelectins
Authors: Chen Lei , Li Jinyi , Yang Guiwen
Published: April 2020

Intelectin (ITLN) is a new type of glycan‐binding lectin. It has been demonstrated to agglutinate bacteria probably due to its carbohydrate‐binding capacity, suggesting its role in an innate immune response. It is involved not only in many physiological processes but also in some human diseases such as asthma, heart disease, inflammatory bowel disease, chronic obstructive pulmonary disease and cancer. Up to now, intelectin orthologs have been identified in placozoans, urochordatas, cephalochordates and several vertebrates, such as cyclostomata, fish, amphibians and mammals. Although the sequences of intelectins in different species are conserved, their expression patterns, quaternary structures and functions differ considerably among and within species. We summarize the evolution of the intelectin gene family, the tissue distribution, structure and functions of intelectins. We conclude that intelectin plays a role in innate immune response and there are still potential functions of intelectin awaiting discovery.
Pattern of human monocyte subpopulations in health and disease
Authors: Ożańska Agnieszka , Szymczak Donata , Rybka Justyna
Published: April 2020

Monocytes are important cells of the innate system. They are a heterogeneous type of cells consisting of phenotypically and functionally distinct subpopulations, which play a specific role in the control, development and escalation of the immunological processes. Based on the expression of superficial CD14 and CD16 in flow cytometry, they can be divided into three subsets: classical, intermediate and non‐classical. Variation in the levels of human monocyte subsets in the blood can be observed in patients in numerous pathological states, such as infections, cardiovascular and inflammatory diseases, cancer and autoimmune diseases. The aim of this review is to summarize current knowledge of human monocyte subsets and their significance in homeostasis and in pathological conditions.
LncRNA XLOC_003810 promotes T cell activation and inhibits PD‐1/PD‐L1 expression in patients with myasthenia gravis‐related thymoma
Authors: Hu Bo , Niu Li , Jiang Zheng , Xu Shenglin , Hu Yong , Cao Kun
Published: April 2020

This study aimed to investigate the effect of long non‐coding RNA XLOC_003810 on the activation of CD4+ T cells and expression of PD‐1/PD‐L1 in patients with myasthenia gravis‐related thymoma (MG‐T). Thymus specimens and thymic mononuclear cells were obtained from MG and MG‐T patients or cardiac surgery patients undergoing thoracotomy who were selected as negative controls (NC). XLOC_003810 expression was examined using quantitative real‐time PCR (qRT‐PCR). Frequency of CD4+ T cells and proportion of CD4+PD‐1+ T cells and CD14+PD‐L1+ monocytes were quantified by flow cytometry. The release of inflammatory cytokines was measured by qRT‐PCR and enzyme‐linked immunosorbent assay. Compared with the NC group, expression of XLOC_003810, frequency of CD4+ T cells and the production of inflammatory cytokines were increased in patients with MG and MG‐T. XLOC_003810 overexpression significantly increased the frequency of CD4+ T cells, facilitated the production of inflammatory cytokines and decreased the proportion of CD4+PD‐1+ T cells and CD14+PD‐L1+ monocytes in the thymic mononuclear cells. In contrast, XLOC_003810 knockdown exerted the opposite effect. Together, XLOC_003810 promotes T cell activation and inhibits PD‐1/PD‐L1 pathway in patients with MG‐T.
Investigating a Mixed-Initiative Workflow for Digital Mind-Mapping
Authors: Chen Ting-Ju , Krishnamurthy Vinayak R.
Published: April 2020

In this paper, we report on our investigation of human-AI collaboration for mind-mapping. We specifically focus on problem exploration in pre-conceptualization stages of early design. Our approach leverages the notion of query expansion—the process of refining a given search query for improving information retrieval. Assuming a mind-map as a network of nodes, we reformulate its construction process as a sequential interaction workflow wherein a human user and an intelligent agent take turns to add one node to the network at a time. Our contribution is the design, implementation, and evaluation of algorithm that powers the intelligent agent (IA). This paper is an extension of our prior work (Chen et al., 2019, “Mini-Map: Mixed-Initiative Mind-Mapping Via Contextual Query Expansion,” AIAA Scitech 2020 Forum, p. 2347) wherein we developed this algorithm, dubbed Mini-Map, and implemented a web-based workflow enabled by ConceptNet (a large graph-based representation of “commonsense” knowledge). In this paper, we extend our prior work through a comprehensive comparison between human-AI collaboration and human-human collaboration for mind-mapping. We specifically extend our prior work by: (a) expanding on our previous quantitative analysis using established metrics and semantic studies, (b) presenting a new detailed video protocol analysis of the mind-mapping process, and (c) providing design implications for digital mind-mapping tools.
Sensitivity of the human auditory cortex and reward network to reverberant musical stimuli
Authors: Lawless Martin S. , Vigeant Michelle C.
Published: April 2020

A room's acoustics can alter subjective impressions of music, including preference. However, little research has characterized the brain's response to room conditions. Functional magnetic resonance imaging (fMRI) was used to investigate the auditory and reward responses to concert hall stimuli. Before the fMRI testing, 18 participants rated their preferences to a solo-instrumental passage and an orchestral motif simulated in eight room acoustic conditions outside an MRI scanner to identify their most liked and disliked conditions. In the MRI, the most-liked (reverberation time, RT = 1.0–2.8 s) and most-disliked (RT = 7.2 s) conditions, along with the [anechoic and scrambled versions] anechoic and scrambled versions of the musical passages were presented. The auditory cortex was found to be sensitive to the temporal coherence of the stimuli as it exhibited stronger activations for simpler stimuli, i.e., the solo-instrumental and anechoic conditions, than for stimuli containing temporally incoherent auditory objects—the orchestral and reverberant conditions. In contrasts between liked and disliked reverberant stimuli, a reward response in the basal ganglia was detected in a region of interest analysis using a temporal derivative model of the hemodynamic response function. This response may indicate differences in preference between subtle variations in room acoustics applied to the same musical passage.
Sex drives T
regs
into fat
Authors: Habrylo Ireneusz , Rosenblum Michael D.
Published: April 2020

Androgens promote inflammation in visceral adipose tissue (VAT), leading to the expansion of a distinct IL-33 producing stromal population and recruitment of T
regs
.
The Novel Immunosuppressive Agent Mycophenolate Mofetil Markedly Potentiates the Antiherpesvirus Activities of Acyclovir, Ganciclovir, and Penciclovir In Vitro and In Vivo
Authors: Neyts Johan , Andrei Graciela , De Clercq Erik
Published: April 2020

The immunosuppressive agent mycophenolate mofetil (MMF) has been approved for use in kidney transplant recipients and may thus be used concomitantly for the treatment of intercurrent herpesvirus infections with drugs such as acyclovir (ACV), ganciclovir (GCV), and penciclovir (PCV). We found that MMF and its parent compound mycophenolic acid (at concentrations that are attainable in plasma) strongly potentiate the antiherpesvirus (herpes simplex virus [HSV] type 1 [HSV-1], HSV-2, thymidine kinase-deficient [TK
−
] HSV-1, both wild-type and TK
−
varicella-zoster virus, and human cytomegalovirus) activities of ACV, PCV, and GCV (up to 350-fold increases in their activities). The mechanism of potentiation was found to reside in the depletion of endogenous dGTP pools, which favored the inhibitory effect of the triphosphate of ACV, GCV, or PCV on the viral DNA polymerase. The combination of topically applied 5% MMF with 0.1% ACV strongly protected against HSV-1-induced cutaneous lesions in hairless mice, whereas therapy with either compound used singly had no protective effect. Interestingly, the combination of topically applied 5% MMF with 5% ACV was also highly effective in protecting against TK
−
HSV-2-induced cutaneous lesions (that were refractory to ACV treatment) in athymic nude mice. Topical therapy with MMF was very well tolerated, and no signs of irritation were observed. When given perorally at 200 mg/kg of body weight/day, MMF potentiated to some extent the growth retardation induced by GCV in young NMRI mice. These observations may have clinical implications (i) for those transplant recipients who receive both MMF and either ACV, GCV, or PCV and (ii) for the treatment of ACV-resistant mucocutaneous HSV infections.
Amino Acid Substitutions in the Cytochrome P-450 Lanosterol 14α-Demethylase (CYP51A1) from Azole-Resistant
Candida albicans
Clinical Isolates Contribute to Resistance to Azole Antifungal Agents
Authors: Sanglard Dominique , Ischer Françoise , Koymans Luc , Bille Jacques
Published: April 2020

The cytochrome P-450 lanosterol 14α-demethylase (CYP51A1) of yeasts is involved in an important step in the biosynthesis of ergosterol. Since CYP51A1 is the target of azole antifungal agents, this enzyme is potentially prone to alterations leading to resistance to these agents. Among them, a decrease in the affinity of CYP51A1 for these agents is possible. We showed in a group of
Candida albicans
isolates from AIDS patients that multidrug efflux transporters were playing an important role in the resistance of
C. albicans
to azole antifungal agents, but without excluding the involvement of other factors (D. Sanglard, K. Kuchler, F. Ischer, J.-L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents Chemother. 39:2378–2386, 1995). We therefore analyzed in closer detail changes in the affinity of CYP51A1 for azole antifungal agents. A strategy consisting of functional expression in
Saccharomyces cerevisiae
of the
C. albicans CYP51A1
genes of sequential clinical isolates from patients was designed. This selection, which was coupled with a test of susceptibility to the azole derivatives fluconazole, ketoconazole, and itraconazole, enabled the detection of mutations in different cloned
CYP51A1
genes, whose products are potentially affected in their affinity for azole derivatives. This selection enabled the detection of five different mutations in the cloned
CYP51A1
genes which correlated with the occurrence of azole resistance in clinical
C. albicans
isolates. These mutations were as follows: replacement of the glycine at position 129 with alanine (G129A), Y132H, S405F, G464S, and R467K. While the S405F mutation was found as a single amino acid substitution in a
CYP51A1
gene from an azole-resistant yeast, other mutations were found simultaneously in individual
CYP51A1
genes, i.e., R467K with G464S, S405F with Y132H, G129A with G464S, and R467K with G464S and Y132H. Site-directed mutagenesis of a wild-type
CYP51A1
gene was performed to estimate the effect of each of these mutations on resistance to azole derivatives. Each single mutation, with the exception of G129A, had a measurable effect on the affinity of the target enzyme for specific azole derivatives. We speculate that these specific mutations could combine with the effect of multidrug efflux transporters in the clinical isolates and contribute to different patterns and stepwise increases in resistance to azole derivatives.
A Rapid Method for Simultaneous Detection of Phenotypic Resistance to Inhibitors of Protease and Reverse Transcriptase in Recombinant Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Antiretroviral Drugs
Authors: Hertogs Kurt , de Béthune Marie-Pierre , Miller Veronica , Ivens Tania , Schel Patricia , Van Cauwenberge Anja , Van den Eynde Christel , van Gerwen Veerle , Azijn Hilde , van Houtte Margriet , Peeters Frank , Staszewski Schlomo , Conant Marcus , Bloor Stuart , Kemp Sharon , Larder Brendan , Pauwels Rudi
Published: April 2020

Combination therapy with protease (PR) and reverse transcriptase (RT) inhibitors can efficiently suppress human immunodeficiency virus (HIV) replication, but the emergence of drug-resistant variants correlates strongly with therapeutic failure. Here we describe a new method for high-throughput analysis of clinical samples that permits the simultaneous detection of HIV type 1 (HIV-1) phenotypic resistance to both RT and PR inhibitors by means of recombinant virus assay technology. HIV-1 RNA is extracted from plasma samples, and a 2.2-kb fragment containing the entire HIV-1 PR- and RT-coding sequence is amplified by nested reverse transcription-PCR. The pool of PR-RT-coding sequences is then cotransfected into CD4
+
T lymphocytes (MT4) with the pGEMT3ΔPRT plasmid from which most of the PR (codons 10 to 99) and RT (codons 1 to 482) sequences are deleted. Homologous recombination leads to the generation of chimeric viruses containing PR- and RT-coding sequences derived from HIV-1 RNA in plasma. The susceptibilities of the chimeric viruses to all currently available RT and/or PR inhibitors is determined by an MT4 cell–3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based cell viability assay in an automated system that allows high sample throughput. The profile of resistance to all RT and PR inhibitors is displayed graphically in a single PR-RT-Antivirogram. This assay system facilitates the rapid large-scale phenotypic resistance determinations for all RT and PR inhibitors in one standardized assay.
Inhibitory Effect of 2′-Fluoro-5-Methyl-β-
l
-Arabinofuranosyl-Uracil on Duck Hepatitis B Virus Replication
Authors: Aguesse-Germon Stéphanie , Liu Shwu-Huey , Chevallier Michèle , Pichoud Christian , Jamard Catherine , Borel Christelle , Chu Chung K. , Trépo Christian , Cheng Yung-Chi , Zoulim Fabien
Published: April 2020

The antiviral activity of 2′-fluoro-5-methyl-β-
l
-arabinofuranosyluracil (
l
-FMAU), a novel
l
-nucleoside analog of thymidine known to be an inhibitor of hepatitis B virus (HBV) replication in hepatoma cells (2.2.1.5 cell line), was evaluated in the duck HBV (DHBV) model. Short-term oral administration (5 days) of
l
-FMAU (40 mg/kg of body weight/day) to experimentally infected ducklings induced a significant decrease in the level of viremia. This antiviral effect was sustained in animals when therapy was prolonged for 8 days. The histological study showed no evidence of liver toxicity in the
l
-FMAU-treated group. By contrast, microvesicular steatosis was found in the livers of dideoxycytidine-treated animals.
l
-FMAU administration in primary duck hepatocyte cultures infected with DHBV induced a dose-dependent inhibition of both virion release in culture supernatants and intracellular viral DNA synthesis, without clearance of viral covalently closed circular DNA. By using a cell-free system for the expression of an enzymatically active DHBV reverse transcriptase, it was shown that
l
-FMAU triphosphate exhibits an inhibitory effect on the incorporation of dAMP in the viral DNA primer. Thus, our data demonstrate that
l
-FMAU inhibits DHBV replication in vitro and in vivo. Long-term administration of
l
-FMAU for the eradication of viral infection in animal models of HBV infection should be evaluated.
Alterations in the GyrA Subunit of DNA Gyrase and the ParC Subunit of DNA Topoisomerase IV Associated with Quinolone Resistance in
Enterococcus faecalis
Authors: Kanematsu Emiko , Deguchi Takashi , Yasuda Mitsuru , Kawamura Takeshi , Nishino Yoshinori , Kawada Yukimichi
Published: April 2020

The
gyrA
and
parC
genes of 31 clinical isolates of
Enterococcus faecalis
, including fluoroquinolone-resistant isolates, were partially sequenced and analyzed for target alterations. Topoisomerase IV may be a primary target in
E. faecalis
, but high-level fluoroquinolone resistance was associated with simultaneous alterations in both GyrA and ParC.
Cytophaga hutchinsonii
gldN
, Encoding a Core Component of the Type IX Secretion System, Is Essential for Ion Assimilation, Cellulose Degradation, and Cell Motility
Authors: Gao Lijuan , Guan Zhiwei , Gao Peng , Zhang Weican , Qi Qingsheng , Lu Xuemei
Published: April 2020

The widespread Gram-negative bacterium
Cytophaga hutchinsonii
uses a novel but poorly understood strategy to utilize crystalline cellulose. Recent studies showed that a T9SS exists in
C. hutchinsonii
and is involved in cellulose degradation and motility. However, the main components of the
C. hutchinsonii
T9SS and their functions are still unclear. Our study characterized the function of GldN, which is a core component of the T9SS. GldN was proved to play vital roles in cellulose degradation and cell motility. Notably, GldN is essential for the acquisition of Ca
2+
and Mg
2+
ions under Ca
2+
- and Mg
2+
-deficient conditions, revealing a link between the T9SS and the metal ion transport system. The outer membrane abundance of CHU_2807, which is essential for Ca
2+
and Mg
2+
uptake in PY6 medium, was affected by the deletion of GldN. This study demonstrated that the
C. hutchinsonii
T9SS has extensive functions, including cellulose degradation, motility, and metal ion assimilation, and contributes to further understanding of the function of the T9SS in the phylum
Bacteroidetes
.
A Molecular Determinant of West Nile Virus Secretion and Morphology as a Target for Viral Attenuation
Authors: Basset Justine , Burlaud-Gaillard Julien , Feher Maxence , Roingeard Philippe , Rey Félix A. , Pardigon Nathalie
Published: April 2020

West Nile virus (WNV) is a worldwide (re)emerging mosquito-transmitted
Flavivirus
causing fatal neurological diseases in humans. However, no human vaccine has been yet approved. One of the most effective live-attenuated vaccines was empirically obtained by serial passaging of wild-type yellow fever
Flavivirus
. However, such an approach is not acceptable nowadays, and the development of a rationally designed vaccine is necessary. Generating molecular infectious clones and mutating specific residues known to be involved in
Flavivirus
virulence constitute a powerful tool to promote viral attenuation. WNV membrane glycoprotein is thought to carry such essential determinants. Here, we identified two residues of this protein whose substitutions are key to the full and stable attenuation of WNV
in vivo
, most likely through inhibition of secretion and possible alteration of morphology. Applied to other flaviviruses, this approach should help in designing new vaccines against these viruses, which are an increasing threat to global human health.
Complete Chromosomal Sequences of Two Borrelia miyamotoi Samples Obtained from Ixodes ricinus Eggs in Czechia
Authors: Janeček Jan , Nováková Markéta , Oppelt Jan , Pospíšilová Petra , Cunha Anita , Silva Ana Catarina , Dantong Li , Šmajs David
Published: April 2020

Here, we present complete chromosome sequences of
Borrelia miyamotoi
samples CZ-F1E and CZ-F190E, which were obtained from
Ixodes ricinus
eggs from Czechia. The chromosome sequences, assembled from Illumina and Sanger sequencing data, had average coverage values of 647× and 3,216×, respectively. They belong to the European genotype, distinct from the Asian and American strains.
Arc-to-craton: Devonian air-fall tephras in the eastern United States
Authors: Ver Straeten* C.A. , Over* D.J. , Baird* G.C.
Published: April 2020

More than 100 air-fall volcanic tephra beds are currently documented from Devonian strata in the eastern United States. These beds act as key sources of various geological data. These include within-basin to basin-to-basin correlation, globally useful geochronologic age dates, and a relatively detailed, if incomplete, record of Acadian–Neoacadian silicic volcanism. The tephras occur irregularly through the vertical Devonian succession, in clusters of several beds, or scattered as a few to single beds. In this contribution, their vertical and lateral distribution and recent radiometric dates are reviewed. Current unresolved issues include correlation of the classic Eifelian-age (lower Middle Devonian) Tioga tephras and dates related to the age of the Onondaga-Marcellus contact in the Appalachian Basin. Here, we used two approaches to examine the paleovolcanic record of Acadian–Neoacadian silicic magmatism and volcanism. Reexamination of volcanic phenocryst distribution maps from the Tioga tephras indicates not one but four or more volcanic sources along the orogen, between southeastern Pennsylvania and northern North Carolina. Finally, radiometric and relative ages of the sedimentary basin tephras are compared and contrasted with current radiometric ages of igneous rocks from New England. Despite data gaps and biases in both records, their comparisons provide insights into Devonian silicic igneous activity in the eastern United States, and into various issues of recognition, deposition, and preservation of tephras in the sedimentary rock record.
Infliximab in acute severe colitis: getting the right dose
Authors: Fiske Joseph , Conley Thomas , Sebastian Shaji , Subramanian Sreedhar
Published: April 2020

Acute severe colitis is a medical emergency and requires prompt treatment with intravenous steroids. Infliximab is typically used as rescue therapy in those who fail to respond to corticosteroids. This article outlines the altered pharmacokinetics of infliximab in acute severe UC and summarised the latest published data surrounding accelerated infliximab dosing.
BowelScope: Accuracy of Detection Using Endocuff Optimisation of Mucosal Abnormalities (the B-ADENOMA Study): a multicentre, randomised controlled flexible sigmoidoscopy trial
Authors: Rees Colin J , Brand Andrew , Ngu Wee Sing , Stokes Clive , Hoare Zoe , Totton Nicola , Bhandari Pradeep , Sharp Linda , Bastable Alexandra , Rutter Matthew D , Verma Ajay Mark , Lee Thomas J , Walls Martin
Published: April 2020

Objectives

Adenoma detection rate (ADR) is an important quality marker at lower GI endoscopy. Higher ADRs are associated with lower postcolonoscopy colorectal cancer rates. The English flexible sigmoidoscopy (FS) screening programme (BowelScope), offers a one-off FS to individuals aged 55 years. However, variation in ADR exists. Large studies have demonstrated improved ADR using Endocuff Vision (EV) within colonoscopy screening, but there are no studies within FS. We sought to test the effect of EV on ADR in a national FS screening population.

Design

BowelScope: Accuracy of Detection Using ENdocuff Optimisation of Mucosal Abnormalities was a multicentre, randomised controlled trial involving 16 English BowelScope screening centres. Individuals were randomised to Endocuff Vision-assisted BowelScope (EAB) or Standard BowelScope (SB). ADR, polyp detection rate (PDR), mean adenomas per procedure (MAP), polyp characteristics and location, participant experience, procedural time and adverse events were measured. Comparison of ADR within the trial with national BowelScope ADR was also undertaken.

Results

3222 participants were randomised (53% male) to receive EAB (n=1610) or SB (n=1612). Baseline demographics were comparable between arms. ADR in the EAB arm was 13.3% and that in the SB arm was 12.2% (p=0.353). No statistically significant differences were found in PDR, MAP, polyp characteristics or location, participant experience, complications or procedural characteristics. ADR in the SB control arm was 3.1% higher than the national ADR.

Conclusion

EV did not improve BowelScope ADR when compared with SB. ADR in both arms was higher than the national ADR. Where detection rates are already high, EV is unable to improve detection further.

Trial registration numbers

NCT03072472,ISRCTN30005319and CPMS ID 33224.
Treating traumatic injuries of canine teeth in cats
Authors: Oxford Matthew
Published: April 2020

Background

Cats frequently suffer dental trauma to their canine teeth, as a result of road traffic accidents, falls or fights with other animals. However, there is limited veterinary literature about the incidence and treatment options for such injuries.

Aim of the article

This article outlines how to treat traumatic injuries of canine teeth in cats by using endodontic or extraction techniques.
Influence of thrombectomy volume on non-physician staff burnout and attrition in neurointerventional teams
Authors: Fargen Kyle M , Ansari Sameer A , Spiotta Alejandro , Dabus Guilherme , Mokin Maxim , Brown Patrick , Wolfe Stacey Q , Kittel Carol , Kan Peter , Baxter Blaise W , De Leacy Reade , Milburn James , Munich Stephan A , Ducruet Andrew F , Reeves Alan , Fraser Justin F , Starke Robert M , Jadhav Ashutosh P , Mack William J , Arthur Adam S , Pride Lee , Sheth Sunil A , Rai Ansaar T , Leslie-Mazwi Thabele , Hirsch Joshua A
Published: April 2020

Background

Burnout takes a heavy toll on healthcare providers. We sought to assess the prevalence and risk factors for burnout among neurointerventional (NI) non-physician procedural staff (nurses and technologists) given increasing thrombectomy demands.

Methods

A 41-question online survey containing questions including the Maslach Burnout Inventory-Human Services Survey for Medical Personnel was distributed to NI nurses and radiology technologists at 20 US endovascular capable stroke centers.

Results

244 responses were received (64% response rate). Median (IQR) composite scores for emotional exhaustion were 25 (15–35), depersonalization 6 (2–11), and personal accomplishment 39 (35–43). Fifty-one percent of respondents met established criteria for burnout. There was no significant relationship between hospital thrombectomy volume, call frequency, call cases covered, or length of commute. On multiple logistic regression analysis, feeling under-appreciated by hospital leadership (OR 4.1; P<0.001) and working with difficult/unpleasant physicians (OR 1.2; P=0.05) were strongly associated with burnout. At participating centers, nurse and technologist attrition was 25% over the previous year. Over 50% of respondents indicated they had strongly considered leaving their position over the last 2 years.

Conclusions

This survey of US NI non-physician procedural staff demonstrates a self-reported burnout prevalence of 51%. This was driven more by interaction with leadership and physician staff than by thrombectomy procedural volume and stroke call. Attrition among NI non-physician procedural staff is high.
African–American and Caucasian mortalities are the same after traumatic injury: pair matched analysis from a national data
Authors: Ahmed Nasim , Kountz David , Kuo Yenhong
Published: April 2020

Background

African–Americans have worse outcomes than Caucasians in many clinical conditions studied, including trauma. We sought to analyze if mortality is different in these groups through analysis of a national data set.

Methods

Recent data from the national Trauma Quality Improvement Program were assessed with analysis, including all African–American or Caucasian patients who were brought to level I or level II trauma centers for care. Propensity scores were calculated for each African–American patient using age, sex, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), injury type, insurance information and American College of Surgeons trauma level. The primary outcome of this study was in-hospital mortality, and the secondary outcomes were hospital length of stay and discharge disposition.

Results

A total of 82 150 (13.65%) out of 601 768 patients who qualified for the inclusion in the study were African–American. The remaining 519 618 (86.35%) were Caucasian. The median age (IQR) of the patients was 54 (33 to 72) years old, and approximately two-thirds of the patients were male. The median ISS and GCS score were 12 (9 to 17) and 15 (15 to 15), respectively. More than 90% of patients sustained blunt injuries. Overall, there was no significant difference found in overall in-hospital mortality between Caucasians and African–American patients (3% vs. 2.9%, p=0.2); however, the median (95% CI) hospital length of stay was 1 day longer in African–American patients compared with Caucasian patients (5 (5.5) vs. 4 (4.4), p<0.001). When the discharged destinations between the two groups were compared, a higher proportion of Caucasians were discharged to home without services (66% vs. 33%).

Conclusion

Our study showed that trauma mortalites among African–American and Caucasians are the same. Efforts to mitigate the ethnic and racial biases in the delivery of healthcare should continue, and these results (no differences in mortality) should be validated in other clinical settings.

Level of evidence

Level II.
Variability in anuran advertisement call: a multi-level study with 15 species of monkey tree frogs (Anura, Phyllomedusidae)
Authors: Röhr David L. , Camurugi Felipe , Paterno Gustavo B. , Gehara Marcelo , Juncá Flora A. , Álvares Guilherme F.R. , Brandão Reuber A. , Garda Adrian A.
Published: April 2020

Understanding the variability of acoustic signals is a first important step for the comprehension of the evolutionary processes that led to current diversity. Herein, we evaluate the variability of the advertisement call of the phyllomedusid species from the genera Phyllomedusa Wagler, 1830 and Pithecopus Cope, 1866 at different levels: intra-individual, intra-population, inter-population, intra-species, and inter-specific. An analysis of coefficients of variation showed a continuum of variability between the acoustic parameters analyzed, from static to highly dynamic. The majority of the variation was attributed to the inter-specific level, while call parameters at the intra-individual level varied the least. However, each parameter behaved differently with call interval being the most variable across all levels. Most temporal acoustic parameters were affected by environmental temperature, while pulse rate and dominant frequency were strongly influenced by body size. Only pulse rate was correlated to the geographic distance between populations, while all parameters presented a significant phylogenetic signal. Based on these results, we discuss the possible importance of different evolutionary forces and the usage of vocalizations for taxonomic purposes.
Chiral symmetry and Heun’s equation
Authors: Choun Yoon-Seok , Sin Sang-Jin
Published: April 2020

We show that the current quark mass should vanish to be consistent with the QCD color confinement: a bag model leads us to Heun’s equation, which requests that not only the energy but also the string tension should be quantized. This is due to the presence of higher-order singularity which requests higher regularity condition demanding that parameters of the theory should be related to one another. As a result, the Hadron spectrum is consistent with the Regge trajectory only when quark mass vanishes. Therefore, in this model, the chiral symmetry is a consequence of the confinement.
Analysis of the Ωb(6316), Ωb(6330), Ωb(6340) and Ωb(6350) with QCD sum rules
Authors: Wang Zhi-Gang
Published: April 2020

In this paper, we introduce an explicit [Formula: see text]-wave to construct three-quark currents to study the [Formula: see text]-wave [Formula: see text] states with the full QCD sum rules. The predicted masses have a hierarchy if the same parameters are chosen and favor assigning the [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] to be the [Formula: see text]-wave [Formula: see text] states with the [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], respectively.
Mapping between different cosmological eras in scale-covariant formalism
Authors: Ribas Marlos O. , Devecchi Fernando P. , Kremer Gilberto M.
Published: April 2020

In this work we consider the scale-covariant formalism proposed by Canuto et al.,[Formula: see text] in order to map different eras of the universe. This technique considers a scale gauge function that can be adjusted by using different arguments like Dirac’s large numbers hypothesis or a restriction on the particle production rate. A Chaplygin constituent shows to be a consistent idea to establish a mapping between an old decelerated–accelerated universe ruled by Einstein equations and an early universe, where a new equation of state appears together with a modified general relativity theory and a de Sitter universe then emerges. These properties are a direct consequence of the use of the scale-covariant formalism. Besides, a new discussion and remarks are presented related to the well-known barotropic constituent case.
Custom Processing
Authors: Vizard Michael , Hofstee Peter
Published: April 2020

Today we’re going to talk about system on a chip and some of the design issues that go with that, and more importantly, some of the newer trends, such as the work that IBM is doing around the cell processor to advance the whole system on a chip processor. To that end, we’ve invited Peter Hofstee, Chief Scientist for the cell processor project that is being funded by IBM, Toshiba, and Sony, to talk to us today about how the whole system on a chip marketplace might change in the advent of the invention of the cell processor, and what technology is driving that.
Embedded systems engineering with the AADL
Authors: Gluch David
Published: April 2020

The SAE Architecture Analysis & Design Language (AADL) is an architecture description language for real-time, fault-tolerant, scalable, embedded, modular multiprocessor systems. It enables the development of highly evolvable systems, early and quantitative analyses of a system's architecture, and evolution of an architecture model for continued analysis throughout the lifecycle. In this tutorial, we provide an overview of the AADL; demonstrate the AADL's capabilities in creating and analyzing component-based models of the task and task interaction architectures of embedded software; discuss interfacing to physical devices; highlight AADL capabilities for predictive analyses of operational characteristics such as meeting deadline, response time, and throughput requirements; and describe how the AADL can discover system integration problems early in a development effort.
Service oriented architecture (SOA) concepts and implementations
Authors: Sward Ricky E.
Published: April 2020

This tutorial covers the principles of Service-Oriented Architectures (SOA) including loose coupling, encapsulation, reusability, composibility, etc. The attendee will learn about the Ada Web Server (AWS) and how SOA interfaces, session management, etc. are implemented using AWS. The tutorial will also cover the fundamentals of the Enterprise Service Bus (ESB), a key enabling component of the SOA. Attendees will learn about ESB endpoints, data routing, automatic translations, etc. They will also learn how to connect Ada web services to an ESB, how to expose the web services, and how to use AWS with the ESB through in-class exercises and demonstrations.
Multi-language programming with Ada
Authors: Ochem Quentin
Published: April 2020

Building complex applications often requires putting together pieces of software or requirements that have not been made to work together in the first place. Thinking of a project with a high integrity kernel written in Ada, using a set of low level libraries and drivers written in C or C++, with a graphical interface done in Java and unit tests driven by python is not thinking of sciencefiction anymore. It's actual concrete and day-to-day work. Unfortunately, having all of these technologies talking to each other is not straightforward, and often requires a deep knowledge of both sides of the technology and extensive manual work.

In this tutorial, we'll first study how to interface directly Ada with native languages, such as C or C++. We'll then have a deep look at communications with languages running on virtual machines, such as Java, Python and the .NET framework. Finally, we'll see how Ada can be interfaced with an arbitrary language using a middleware solution, such as SOAP or CORBA We?ll see how the communication can be manually done using low level features and APIs, and how a substantial part of this process can be automated using high level binding generators.
On using Ada to solve problems in computational economics and related disciplines with concurrent, multiagent algorithms
Authors: Barkstrom Bruce R.
Published: April 2020

Multiagent algorithms are widely used in computational economics and other social sciences to solve theoretical and practical problems. Because such algorithms are inherently concurrent and multithreaded, Ada's constructs for handling communications between concurrent processes and avoiding interference between them make the language very well suited to solving these problems, particularly given developments in multi-core CPU chip-making. This paper provides a concrete example of how Ada assists in solving problems in computational economics and related disciplines that work with multiagent systems. Solving a simple problem illustrates visualizing the agents as Ada tasks, using UML use cases and synchronization diagrams to design the communications patterns between agents, and applying protected objects and functions to avoid computational indeterminacy.
Use of SPARK in a resource constrained embedded system
Authors: Loseby Chad , Chapin Peter , Brandon Carl
Published: April 2020

We are constructing a remote sensing buoy that will be deployed on the Arctic sea ice north of Alaska. The buoy will gather environmental data and transmit that data back to home base via the Iridium satellite network. This data will then be used (by others) to refine models of ice movement. To enhance reliability the buoy software was written using SPARK Ada. SPARK was also helpful in reducing the memory footprint of the software to an acceptable level. Note also that the construction of the prototype buoy is a student project. Thus our experience is in an educational context.
A robotics API dialect for type-safe robots
Authors: Mentis Alexander S.
Published: April 2020

In this paper, we present an Ada robotics API designed to be used in teaching undergraduate-level computer science. Our API is inspired by Myro, a Python-based API, but we improve upon Myro's usability, readability, modularity, and documentation by using features of the Ada programming language and the GNAT Programming Studio's documentation generation tool. The encapsulation, abstraction, and data hiding provided by Ada's packages make it easy for beginning programmers to use the API for advanced tasks, while Ada's syntax and readability allow educators to use the underlying code later in a course or curriculum to illustrate more advanced concepts to the same students as their knowledge and experience grow.
The new semantic model in ASIS for Ada 2005
Authors: Rosen Jean-Pierre , Taft Tucker
Published: April 2020

Following the new Ada 2005 standard, the ASIS interface has to be upgraded. In addition to supporting the representation of new features, ASIS has been extended with a
semantic
subsystem, where queries support the logical views of entities rather than their syntactic counterparts. This paper describes the new concepts introduced by this new subsystem.
Looking beyond a singularity
Authors: Hunt Galen C.
Published: April 2020

How does one build a truly dependable software system? Seven years ago, Microsoft Research started the Singularity project to answer this question. The premise was to start with the best known software development tools and to build a new kind of operating system from the ground up. The operating system was to be both an output artifact and a laboratory for the research. Portions of the code and ideas have been incorporated into three separate Microsoft operating systems so far. I will give a brief overview of Singularity planned and built, then describe what we learned, both positive and negative. I will speculate on OS futures including current research to build an operating system in which every last assembly instruction has been verified for type safety, a system for truly mobile computation, and new tools for automatically restructuring large software systems.
Energy-efficient storage in virtual machine environments
Authors: Ye Lei , Lu Gen , Kumar Sushanth , Gniady Chris , Hartman John H.
Published: April 2020

Current trends in increasing storage capacity and virtualization of resources combined with the need for energy efficiency put a challenging task in front of system designers. Previous studies have suggested many approaches to reduce hard disk energy dissipation in native OS environments; however, those mechanisms do not perform well in virtual machine environments because a virtual machine (VM) and the virtual machine monitor (VMM) that runs it have different semantic contexts. This paper explores the disk I/O activities between VMM and VMs using trace driven simulation to understand the I/O behavior of the VM system. Subsequently, this paper proposes three mechanisms to address the isolation between VMM and VMs, and increase the burstiness of hard disk accesses to increase energy efficiency of a hard disk. Compared to standard shutdown mechanisms, with eight VMs the proposed mechanisms reduce disk spin-ups, increase the disk sleep time, and reduce energy consumption by 14.8% with only 0.5% increase in execution time. We implemented the proposed mechanisms in Xen and validated our simulation results.
Supporting soft real-time tasks in the xen hypervisor
Authors: Lee Min , Krishnakumar A. S. , Krishnan P. , Singh Navjot , Yajnik Shalini
Published: April 2020

Virtualization technology enables server consolidation and has given an impetus to low-cost green data centers. However, current hypervisors do not provide adequate support for real-time applications, and this has limited the adoption of virtualization in some domains. Soft real-time applications, such as media-based ones, are impeded by components of virtualization including low-performance virtualization I/O, increased scheduling latency, and shared-cache contention. The virtual machine scheduler is central to all these issues. The goal in this paper is to adapt the virtual machine scheduler to be more soft-real-time friendly.

We improve two aspects of the VMM scheduler -- managing scheduling latency as a first-class resource and managing shared caches. We use enterprise IP telephony as an illustrative soft real-time workload and design a scheduler S that incorporates the knowledge of soft real-time applications in
all
aspects of the scheduler to support responsiveness. For this we first define a
laxity
value that can be interpreted as the target scheduling latency that the workload desires. The load balancer is also designed to minimize the latency for real-time tasks. For cache management, we take cache-affinity into account for real time tasks and load-balance accordingly to prevent cache thrashing. We measured cache misses and demonstrated that cache management is essential for soft real time tasks. Although our scheduler S employs a different design philosophy, interestingly enough it can be implemented with simple modifications to the Xen hypervisor's credit scheduler. Our experiments demonstrate that the Xen scheduler with our modifications can support soft real-time guests well, without penalizing non-real-time domains.
Application of model based development to flexible code generation
Authors: Shubert Gary J.
Published: April 2020

This address will present the authors views and perspectives on the past, present and future use of model based development techniques to enable the automated generation of source code and other forms of programming. This address will discuss past and present use of model based development and automated code generation at Lockheed Martin, with special emphasis on NASA's Orion Multi-Purpose Crew Vehicle Program. This address will discuss the advantages and disadvantages, associated with the current state of the practice techniques and tools, used to automatically generate source code from general purpose and domain specific models. This address will discuss the obstacles and enablers, associated with achieving the desired future state of complete and efficient automated generation of programming through transformation of general purpose and domain specific models.
WCET-aware re-scheduling register allocation for real-time embedded systems with clustered VLIW architecture
Authors: Huang Yazhi , Zhao Mengying , Xue Chun Jason
Published: April 2020

Worst-Case Execution Time (WCET) is one of the most important metrics in real-time embedded system design. For embedded systems with clustered VLIW architecture, register allocation, instruction scheduling, and cluster assignment are three key activities to pursue code optimization which have profound impact on WCET. At the same time, these three activities exhibit a phase ordering problem: Independently performing register allocation, scheduling and cluster assignment could have a negative effect on the other phases, thereby generating sub-optimal compiled codes. In this paper, a compiler level optimization, namely
WCET-aware Re-scheduling Register Allocation
(WRRA), is proposed to achieve WCET minimization for real-time embedded systems with clustered VLIW architecture. The novelty of the proposed approach is that the effects of register allocation, instruction scheduling and cluster assignment on the quality of generated code are taken into account for WCET minimization. These three compilation processes are integrated into a single phase to obtain a balanced result. The proposed technique is implemented in Trimaran 4.0. The experimental results show that the proposed technique can reduce WCET effectively, by 33% on average.