bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic SREK1 decrease in Huntington’s disease lowers TAF1 mimicking X-linked dystonia parkinsonism
Authors: Hernández Ivó H , Cabrera Jorge R , Santos-Galindo María , Sánchez-Martín Manuel , Domínguez Verónica , García-Escudero Ramón , Pérez-Álvarez María J , Pintado Belén , Lucas José J
Published: May 2020

Huntington’s disease and X-linked dystonia parkinsonism are two monogenic basal ganglia model diseases. Huntington’s disease is caused by a polyglutamine-encoding CAG repeat expansion in the Huntingtin (HTT) gene leading to several toxic interactions of both the expanded CAG-containing mRNA and the polyglutamine-containing protein, while X-linked dystonia parkinsonism is caused by a retrotransposon insertion in the TAF1 gene, which decreases expression of this core scaffold of the basal transcription factor complex TFIID. SRSF6 is an RNA-binding protein of the serine and arginine-rich (SR) protein family that interacts with expanded CAG mRNA and is sequestered into the characteristic polyglutamine-containing inclusion bodies of Huntington’s disease brains. Here we report decreased levels of the SRSF6 interactor and regulator SREK1—another SR protein involved in RNA processing—which includes TAF1 as one of its targets. This led us to hypothesize that Huntington’s disease and X-linked dystonia parkinsonism pathogeneses converge in TAF1 alteration. We show that diminishing SRSF6 through RNA interference in human neuroblastoma cells leads to a decrease in SREK1 levels, which, in turn, suffices to cause diminished TAF1 levels. We also observed decreased SREK1 and TAF1 levels in striatum of Huntington’s disease patients and transgenic model mice. We then generated mice with neuronal transgenic expression of SREK1 (TgSREK1 mice) that, interestingly, showed transcriptomic alterations complementary to those in Huntington’s disease mice. Most importantly, by combining Huntington’s disease and TgSREK1 mice we verify that SREK1 overexpression corrects TAF1 deficiency and attenuates striatal atrophy and motor phenotype of Huntington’s disease mice. Our results therefore demonstrate that altered RNA processing upon SREK1 dysregulation plays a key role in Huntington’s disease pathogenesis and pinpoint TAF1 as a likely general determinant of selective vulnerability of the striatum in multiple neurological disorders.
M1 muscarinic acetylcholine receptor dysfunction in moderate Alzheimer’s disease pathology
Authors: Yi Jee Hyun , Whitcomb Daniel J , Park Se Jin , Martinez-Perez Celia , Barbati Saviana A , Mitchell Scott J , Cho Kwangwook
Published: May 2020

Aggregation of amyloid beta and loss of cholinergic innervation in the brain are predominant components of Alzheimer’s disease pathology and likely underlie cognitive impairment. Acetylcholinesterase inhibitors are one of the few treatment options for Alzheimer’s disease, where levels of available acetylcholine are enhanced to counteract the cholinergic loss. However, these inhibitors show limited clinical efficacy. One potential explanation for this is a concomitant dysregulation of cholinergic receptors themselves as a consequence of the amyloid beta pathology. We tested this hypothesis by examining levels of M1 muscarinic acetylcholine receptors in the temporal cortex from seven Alzheimer’s disease and seven non-disease age-matched control brain tissue samples (control: 85 ± 2.63 years old, moderate Alzheimer’s disease: 84 ± 2.32 years old, P-value = 0.721; eight female and six male patients). The samples were categorized into two groups: ‘control’ (Consortium to Establish a Registry for Alzheimer’s Disease diagnosis of ‘No Alzheimer’s disease’, and Braak staging pathology of I–II) and ‘moderate Alzheimer’s disease’ (Consortium to Establish a Registry for Alzheimer’s Disease diagnosis of ‘possible/probable Alzheimer’s disease’, and Braak staging pathology of IV). We find that in comparison to age-matched controls, there is a loss of M1 muscarinic acetylcholine receptors in moderate Alzheimer’s disease tissue (control: 2.17 ± 0.27 arbitrary units, n = 7, Mod-AD: 0.83 ± 0.16 arbitrary units, n = 7, two-tailed t-test, t = 4.248, P = 0.00113). Using a functional rat cortical brain slice model, we find that postsynaptic muscarinic acetylcholine receptor function is dysregulated by aberrant amyloid beta-mediated activation of metabotropic glutamate receptor 5. Crucially, blocking metabotropic glutamate receptor 5 restores muscarinic acetylcholine receptor function and object recognition memory in 5XFAD transgenic mice. This indicates that the amyloid beta-mediated activation of metabotropic glutamate receptor 5 negatively regulates muscarinic acetylcholine receptor and illustrates the importance of muscarinic acetylcholine receptors as a potential disease-modifying target in the moderate pathological stages of Alzheimer’s disease.
Degeneracy and Redundancy in Active Inference
Authors: Sajid Noor , Parr Thomas , Hope Thomas M , Price Cathy J , Friston Karl J
Published: May 2020

The notions of degeneracy and redundancy are important constructs in many areas, ranging from genomics through to network science. Degeneracy finds a powerful role in neuroscience, explaining key aspects of distributed processing and structure–function relationships in the brain. For example, degeneracy accounts for the superadditive effect of lesions on functional deficits in terms of a “many-to-one” structure–function mapping. In this paper, we offer a principled account of degeneracy and redundancy, when function is operationalized in terms of active inference, namely, a formulation of perception and action as belief updating under generative models of the world. In brief, “degeneracy” is quantified by the “entropy” of posterior beliefs about the causes of sensations, while “redundancy” is the “complexity” cost incurred by forming those beliefs. From this perspective, degeneracy and redundancy are complementary: Active inference tries to minimize redundancy while maintaining degeneracy. This formulation is substantiated using statistical and mathematical notions of degenerate mappings and statistical efficiency. We then illustrate changes in degeneracy and redundancy during the learning of a word repetition task. Finally, we characterize the effects of lesions—to intrinsic and extrinsic connections—using in silico disconnections. These numerical analyses highlight the fundamental difference between degeneracy and redundancy—and how they score distinct imperatives for perceptual inference and structure learning that are relevant to synthetic and biological intelligence.
An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019
Authors: Bordoni Veronica , Sacchi Alessandra , Cimini Eleonora , Notari Stefania , Grassi Germana , Tartaglia Eleonora , Casetti Rita , Giancola Maria Letizia , Bevilacqua Nazario , Maeurer Markus , Zumla Alimuddin , Locatelli Franco , De Benedetti Fabrizio , Palmieri Fabrizio , Marchioni Luisa , Capobianchi Maria R , D’Offizi Gianpiero , Petrosillo Nicola , Antinori Andrea , Nicastri Emanuele , Ippolito Giuseppe , Agrati Chiara
Published: May 2020

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.
Case Fatality Risk of the First Pandemic Wave of Coronavirus Disease 2019 (COVID-19) in China
Authors: Deng Xiaowei , Yang Juan , Wang Wei , Wang Xiling , Zhou Jiaxin , Chen Zhiyuan , Li Jing , Chen Yinzi , Yan Han , Zhang Juanjuan , Zhang Yongli , Wang Yan , Qiu Qi , Gong Hui , Wei Xianglin , Wang Lili , Sun Kaiyuan , Wu Peng , Ajelli Marco , Cowling Benjamin J , Viboud Cecile , Yu Hongjie
Published: May 2020

Background

To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals.

Methods

We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from 29 December 2019 to 17 April 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and log-normal distributions to time-to-event data using maximum-likelihood estimation.

Results

We analyzed 82 719 laboratory-confirmed cases reported in mainland China, including 4632 deaths and 77 029 discharges. The estimated CFR was 5.65% (95% confidence interval [CI], 5.50–5.81%) nationally, with the highest estimate in Wuhan (7.71%) and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients and 0.8–10.3-fold higher than that of mild-to-severe patients. Older age (odds ratio [OR], 1.14 per year; 95% CI, 1.11–1.16) and being male (OR, 1.83; 95% CI, 1.10–3.04) were risk factors for mortality. The times from symptom onset to first healthcare consultation, to laboratory confirmation, and to hospitalization were consistently longer for deceased patients than for those who recovered.

Conclusions

Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.
The riskscapes of re/insurance
Authors: Taylor Zac J , Weinkle Jessica L
Published: May 2020

Property catastrophe re/insurance plays a crucial yet underexplored role in the governance of disparate geographies of risk. This article extends the concept of the riskscape to the study of re/insurance in two ways. We first develop a four-part framework for understanding re/insurance markets as a series of conjoined riskscapes. Second, we apply this approach to a case study analysis of Florida’s hurricane wind re/insurance market and its restructuring after the destructive 2004/2005 hurricane seasons. Using this riskscapes framework and the Florida case, we advance a critical geographical understanding of re/insurance markets as conjunctural and open-ended political economic projects.
Clinical Performance of Two SARS-CoV-2 Serologic Assays
Authors: Tang Mei San , Hock Karl G , Logsdon Nicole M , Hayes Jennifer E , Gronowski Ann M , Anderson Neil W , Farnsworth Christopher W
Published: May 2020

Background

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a rapid proliferation of serologic assays. However, little is known about their clinical performance. Here, we compared two commercial SARS-CoV-2 IgG assays.

Methods

103 specimens from 48 patients with PCR-confirmed SARS-CoV-2 infections and 153 control specimens were analyzed using SARS-CoV-2 serologic assays by Abbott and EUROIMMUN (EI). Duration from symptom onset was determined by medical record review. Diagnostic sensitivity, specificity, and concordance were calculated.

Results

The Abbott SARS-CoV-2 assay had a diagnostic specificity of 99.4% (95% CI; 96.41–99.98%), and sensitivity of 0.0% (95% CI; 0.00–26.47%) at <3 days post symptom onset, 30.0% (95% CI; 11.89–54.28) at 3–7d, 47.8% (95% CI; 26.82–69.41) at 8–13d and 93.8% (95% CI; 82.80–98.69) at ≥14d. Diagnostic specificity on the EI assay was 94.8% (95% CI; 89.96–97.72) if borderline results were considered positive and 96.7% (95% CI; 92.54–98.93) if borderline results were considered negative. The diagnostic sensitivity was 0.0% (95% CI; 0.00–26.47%) at <3d, 25.0% (95% CI; 8.66–49.10) at 3–7d, 56.5% (95% CI; 34.49–76.81) at 3–7d and 85.4% (95% CI; 72.24–93.93) at ≥14d if borderline results were considered positive. The qualitative concordance between the assays was 0.83 (95% CI; 0.75–0.91).

Conclusion

The Abbott SARS-CoV-2 assay had fewer false positive and false negative results than the EI assay. However, diagnostic sensitivity was poor in both assays during the first 14 days of symptoms.
QoS Enhancement In VoD Systems: Load Management And Replication Policy Optimization Perspectives
Authors: Alaya Bechir , Khan Rehanullah
Published: May 2020

The amount of online video content is exponentially increasing, which spurs its access demands. Providing optimal quality of service (QoS) for this ever-increasing video data is a challenging task due to the number of QoS constraints. The system resources, the distributed system platform and the transport protocol thus all need to collaborate to guarantee an acceptable level of QoS for the optimal video streaming process. In this paper, we present a comprehensive survey on QoS management for the video-on-demand systems. First, we focus on load management and replication algorithms in content delivery networks and peer-to-peer (P2P) networks for their shortcomings. We also address the problem of admission control and resource allocation with the objectives of congestion avoidance and frame-loss reduction. Besides, we introduce and discuss various replication schemes. For both the client–server architecture and P2P networks, we highlight the need for a specific storage management policy to preserve system reliability and content availability. We also focus on content distribution and streaming protocols scaling. We deduce that content availability is linked to the characteristics and the performance of the streaming protocols. Finally, we create a comparison table that presents the different contributions of the discussed approaches as well as their limitations. We believe that such a comprehensive survey provides useful insights and contributes to the related domains.
Safety and Optimal Timing of BCG Vaccination in Infants Born to Mothers Receiving Anti-TNF Therapy for Inflammatory Bowel Disease
Authors: Park Sang Hyoung , Kim Hyo Jong , Lee Chang Kyun , Song Eun Mi , Kang Sang-Bum , Jang Byung Ik , Kim Eun Soo , Kim Kyeong Ok , Lee Yoo Jin , Kim Eun Young , Jung Yun Jin , Park Soo-Kyung , Park Dong Il , Ye Byong Duk , Jung Sung-Ae , Yang Suk-Kyun
Published: May 2020

Backgrounds and Aims

We aimed to evaluate the safety of Bacille Calmette–Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease.

Methods

Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30.

Results

After receiving BCG vaccination at a median age of 6 months [range, 0.25–11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death.

Conclusions

BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero.
VALIDation of the IBD-Disk Instrument for Assessing Disability in Inflammatory Bowel Diseases in a French Cohort: The VALIDate Study
Authors: Le Berre Catherine , Flamant Mathurin , Bouguen Guillaume , Siproudhis Laurent , Dewitte Marie , Dib Nina , Cesbron-Metivier Elodie , Goronflot Thomas , Hanf Matthieu , Gourraud Pierre-Antoine , Kerdreux Elise , Poinas Alexandra , Bourreille Arnaud , Trang-Poisson Caroline
Published: May 2020

Background and Aims

Inflammatory bowel diseases [IBD] are disabling disorders. The IBD-Disability Index [IBD-DI] was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk and to assess the clinical factors associated with a change in the score and its variability over time.

Methods

From May 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3–12 month intervals. Validation included concurrent validity, reproducibility, and internal consistency. Mean IBD-Disk scores were compared according to clinical factors. Variability was assessed by comparing scores between baseline and follow-up visits.

Results

A total of 447 patients [71% Crohn’s disease, 28% ulcerative colitis] were included in the analysis at baseline and 265 at follow-up. There was a good correlation between IBD-Disk and IBD-DI [r = 0.75, p <0.001]. Reproducibility was excellent [intra-class correlation coefficient = 0.90], as well as internal consistency [Cronbach’s α = 0.89]. The IBD-Disk was not influenced by IBD type but was associated with female gender and physician global assessment. Extra-intestinal manifestations, history of resection, elevated C-reactive protein and faecal calprotectin also tended to be associated with higher disability. The IBD-Disk score decreased in patients becoming inactive over time.

Conclusions

This study validated the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability for both CD and UC.
Applications of Beauveria bassiana (Hypocreales: Cordycipitaceae) to Control Populations of Spotted Lanternfly (Hemiptera: Fulgoridae), in Semi-Natural Landscapes and on Grapevines
Authors: Clifton Eric H , Hajek Ann E , Jenkins Nina E , Roush Richard T , Rost John P , Biddinger David J
Published: May 2020

Spotted lanternfly, Lycorma delicatula (White), is an invasive Asian insect that was initially found in Berks County, Pennsylvania, in 2014. As of early 2020, this pest had been found in five more eastern states and it is expected to continue to expand its geographical range. Lycorma delicatula is highly polyphagous but seems to prefer tree-of-heaven, Ailanthus altissima. However, grape growers in Pennsylvania have reported significant damage and loss of vines caused by L. delicatula adults. In fall 2018, two fungal entomopathogens (Beauveria bassiana and Batkoa major) drove localized collapses in L. delicatula populations in Berks County, Pennsylvania. In 2019, we tested applications of a commercialized mycoinsecticide based on B. bassiana strain GHA on L. delicatula populations in a public park in southeastern Pennsylvania. A single application of B. bassiana reduced fourth instar nymphs by 48% after 14 d. Applications of B. bassiana to L. delicatula adults in the same park resulted in 43% mortality after 14 d. Beauveria bassiana spores remained viable on foliage for 5–7 d after spraying. We also conducted semi-field bioassays with B. bassiana GHA (formulated as BoteGHA and Aprehend) and another mycoinsecticide containing Isaria fumosorosea Apopka Strain 97 against L. delicatula adults feeding on potted grapes. All the mycoinsecticides killed ≥90% of adults after 9 d using direct applications. Aprehend killed 99% of adults after 9 d with exposure to residues on sprayed grapes. These data show that fungal entomopathogens can help to suppress populations of L. delicatula in agroecosystems and natural areas.
‘Primary’ Factors in Intergenerational Class Mobility in Europe: Results from the Application of a Topological Model
Authors: Bukodi Erzsébet , Goldthorpe John H
Published: May 2020

There is little consensus in past research regarding the sources of cross-national variation in relative rates of intergenerational class mobility. We argue for the importance of distinguishing between ‘primary’ factors that explain why inequalities in relative chances of mobility exist in the first place, and ‘secondary’ factors that explain variation in these chances. Our main aim is to identify primary factors. We follow Erikson and Goldthorpe in developing a topological model of the endogenous mobility regime which we then apply to class mobility tables for 30 European nations. The model claims that inequalities in relative class mobility chances derive from three kinds of effect: those of class hierarchy, class inheritance and status affinity. When applied to all nations together, the model accounts for the very large part of the total association between class origins and destinations. Clear differences, however, show up between the mobility regimes of men and of women: gender is a secondary factor. When the model is applied separately to nations in the high fluidity and low fluidity sets that we distinguish, we find that the effects of the primary factors identified by our model strengthen in a consistent way from the former set to the latter, although it seems likely that different secondary factors may operate in offsetting ways. Finally, when the model is applied to the groups of nations that we distinguish within the high and low fluidity sets, few differences in the strengths of the various effects show up, but those that do are highly concentrated in post-socialist nations and can be related to secondary factors of a specific kind associated with particular features of their transitions to some form of capitalist democracy.
Defining the normal QT interval in newborns: the natural history and reference values for the first 4 weeks of life
Authors: Pærregaard Maria Munk , Hvidemose Sara Osted , Pihl Christian , Sillesen Anne-Sophie , Parvin Solmaz Bagheri , Pietersen Adrian , Iversen Kasper Karmark , Bundgaard Henning , Christensen Alex Hørby
Published: May 2020

Aims

Evaluation of the neonatal QT interval is important to diagnose arrhythmia syndromes and evaluate side effects of drugs. We aimed at describing the natural history of the QT interval duration during the first 4 weeks of life and to provide reference values from a large general population sample.

Methods and results

The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation of newborns. Eight-lead electrocardiograms were obtained and analysed with a computerized algorithm with manual validation. We included 14 164 newborns (52% boys), aged 0–28 days, with normal echocardiograms. The median values (ms, 2–98%ile) for the corrected intervals QTc (Bazett), QTc (Hodges), QTc (Fridericia), and QTc (Framingham) were 419 (373–474), 419 (373–472), 364 (320–414), and 363 (327–405). During the 4 weeks, we observed a small decrease of QTcFramingham, and an increase of QTcHodges (both P < 0.01), while QTcBazett and QTcFridericia did not change (P > 0.05). Applying published QT interval cut-off values resulted in 5–25% of the newborns having QT prolongation. Uncorrected QT intervals decreased linearly with increasing heart rate (HR). Sex and infant size did not affect the QT interval and the gestational age (GA) only showed an effect when comparing the extreme low- vs. high GA groups (≤34 vs. ≥42 weeks, P = 0.021).

Conclusion

During the 4 weeks QTcFramingham and QTcHodges showed minor changes, whereas QTcBazett and QTcFridericia were stable. The QT interval was unaffected by sex and infant size and GA only showed an effect in very premature newborns. Reference values for HR-specific uncorrected QT intervals may facilitate a more accurate diagnosis of newborns with abnormal QT intervals.
Efficacy of high-power and short-duration ablation in patients with atrial fibrillation: a prospective randomized controlled trial
Authors: Shin Dong Geum , Ahn Jinhee , Han Sang-Jin , Lim Hong Euy
Published: May 2020

Aims

The formation of radiofrequency lesions depends on the power and duration of ablation, and the contact force (CF). Although high power (HP) creates continuous and transmural lesions, most centres still use 25–30 W for 30–40 s for safety reasons. We evaluated the clinical efficacy and safety of a HP and short-duration (HPSD) strategy for atrial fibrillation (AF) ablation.

Methods and results

One hundred and fifty patients [58.2 ± 10.0 years, 48% with paroxysmal AF (PAF)] scheduled for index AF ablation using a CF-sensing catheter were randomly assigned to three groups [30 W, 40 W, and 50 W at ablation sites of anterior, roof, and inferior segments of pulmonary vein (PV) antra and roof line between each upper PV]. In 25–30 W for ≤20 s was applied at posterior wall ablation site in all subjects. Compared with the 30 W and 40 W groups, procedure (P < 0.001) and ablation times (P < 0.001) were shorter and ablation number for PV isolation (P < 0.001) was smaller in the 50 W group. There were no significant differences in the CF and ablation index (AI) among the three groups. There were no significant differences in the procedure-related complication rates. During the 12-month follow-up, AF recurred in 24 (16%) patients with no significant difference among the groups (P = 0.769). In the multivariate analysis, non-PAF [hazard ratio (HR) 2.836, P = 0.045] and AI (HR 0.983, P = 0.001) were independent risk factors for AF recurrence.

Conclusion

Radiofrequency ablation with HPSD is a safe and effective strategy with reduced ablation number and shortened procedure time compared to conventional ablation.
Costs and effects of conventional vision screening and photoscreening in the Dutch preventive child health care system
Authors: Van der Ploeg Catharina P B , Grevinga Manon , Eekhout Iris , Vlasblom Eline , Lanting Caren I , van Minderhout H M (Ellen) , van Dijk – van der Poel Jolande , van den Akker-van Marle M Elske , Verkerk Paul H
Published: May 2020

Background

Little is known about costs and effects of vision screening strategies to detect amblyopia. Aim of this study was to compare costs and effects of conventional (optotype) vision screening, photoscreening or a combination in children aged 3–6 years.

Methods

Population-based, cross-sectional study in preventive child health care in The Hague. Children aged 3 years (3y), 3 years and 9 months (3y9m) or 5–6 years (5/6y) received the conventional chart vision screening and a test with a photoscreener (Plusoptix S12C). Costs were based on test duration and additional costs for devices and diagnostic work-up.

Results

Two thousand, one hundred and forty-four children were included. The estimated costs per child screened were €17.44, €20.37 and €6.90 for conventional vision screening at 3y, 3y9m and 5/6y, respectively. For photoscreening, these estimates were €6.61, €7.52 and €9.40 and for photoscreening followed by vision screening if the result was unclear (combination) €9.32 (3y) and €9.33 (3y9m). The number of children detected with amblyopia by age were 9, 14 and 5 (conventional screening), 6, 13 and 3 (photoscreening) and 10 (3y) and 15 (3y9m) (combination), respectively. The estimated costs per child diagnosed with amblyopia were €1500, €1050 and €860 for conventional vision screening, €860, €420 and €1940 for photoscreening and €730 (3y) and €450 (3y9m) for the combination.

Conclusions

Combining photoscreening with vision screening seems promising to detect amblyopia in children aged 3y/3y9m, whereas conventional screening seems preferable at 5/6y. As the number of study children with amblyopia is small, further research on the effects of these screening alternatives in detecting children with amblyopia is recommended.
Is impending or actual death of a spouse with dementia bad for mental health? Antidepressant use surrounding widowhood
Authors: Einiö Elina , Metsä-Simola Niina , Saarioja Saska , Martikainen Pekka , Korhonen Kaarina
Published: May 2020

Background

Previous studies have shown that the risk of death is elevated after the death of a spouse. Limited evidence is available on changes in mental health before and after bereavement among individuals whose spouse dies of dementia.

Methods

We analyzed changes in the 3-month prevalence of antidepressant use for 5 years before and 3 years after widowhood for individuals whose spouses died of either dementia or other causes. The study used data of 41 855 widowed individuals and repeated-measures logistic regression analyses. Antidepressant use was based on the prescription register of Finland in 1995–2007.

Results

Five years before widowhood, the 3-month prevalence for antidepressant use was 4% among widowing men and 6–7% among widowing women, regardless of whether the spouse died of dementia or other causes. Further changes in antidepressant use depended on a spouse’s cause of death. Women whose spouses died of dementia experienced large increase in antidepressant use starting from 3 to 4 years prior to widowhood, whereas other widows did not experience large increase until after widowhood. The trajectories for men were similar. Antidepressant use following the death of a spouse with dementia stayed at a new heightened level after widowhood.

Conclusions

The trajectories of antidepressant use indicate that the process of losing a spouse to dementia is bad for mental health, already a few years prior to widowhood. There are no clear improvements in mental health after the death of a spouse with dementia. Support services for individuals whose spouses’ dementia progresses are needed.
Beyond the dual revolution: revisiting capitalism in modern France
Authors: Yates Alexia , Vause Erika
Published: May 2020

Abstract—

What communication has there been—and should there be—between the history of modern France and the new history of capitalism? In this introduction to a special issue, the authors trace the recent development of a new scholarly interest in the history of capitalism, outlining the ways that this field intersects with existing research on the history of economic life in nineteenth-century France and suggesting how historians of France can push this scholarship into new directions. In particular, French history’s global turn, the strength of historiography on consumerism and marketization, the place of (revolutionary) property in law and culture and the significance of cultural history represent particular vectors through which the history of nineteenth-century France and the new history of capitalism can develop.
The Land of Cockaigne: The German Art Market and the First World War*
Authors: Alvi Maddalena
Published: May 2020

This article reconstructs changes in the German art market during the First World War on the basis of an art-price index for the years 1910 to 1918. The art market during the war was closely tied to the monetary deterioration of the German economy, which undermined trust in paper money. Through an analysis of prices and auction reports, this article shows that from 1916 onwards, the public invested in art, evidence that the pattern of expenditure for tangible assets more commonly associated with postwar hyperinflation had already taken off during the war. At the same time, the First World War precipitated the disintegration of a bourgeois milieu of collectors, marking a transition from the traditional market into a modern and rational auction more open to speculative incentives. The inflow of new buyers shook the hierarchies and conventions of the market. Reports published in the auction journal Der Kunstmarkt provide insight into the reactions of insiders from Germany’s Bildungsbürgertum to this transformation. The more visible the monetary value of art, the bigger these insiders’ contempt for newcomers, whom they found guilty of overthrowing the rules of patronage of the old market. Derogatory depictions of new buyers as either investors or war profiteers were a means for insiders to define their own socio-cultural standing at a time of crisis, establishing a pattern that would subsequently characterize many postwar debates on both politics and culture.
What Can We Learn From the Past About the Future of Gerontology: Using Natural Language Processing to Examine the Field of Gerontology
Authors: Ayalon Liat , Lev Sagit , Lev Gil
Published: May 2020

Objectives

We thematically classified all titles of eight top psychological and social gerontology journals over a period of six decades, between 1961 and February 2020. This was done in order to provide a broad overview of the main topics that interest the scientific community over time and place.

Method

We used natural language processing in order to analyze the data. In order to capture the diverse thematic clusters covered by the journals, a cluster analysis, based on “topic detection” was conducted.

Results

A total of 15,566 titles were classified into 38 thematic clusters. These clusters were then compared over time and geographic location. The majority of titles fell into a relatively small number of thematic clusters and a large number of thematic clusters were hardly addressed. The most frequently addressed thematic clusters were (a) Cognitive functioning, (b) Long-term care and formal care, (c) Emotional and personality functioning, (d) health, and (e) Family and informal care. The least frequently addressed thematic clusters were (a) Volunteering, (b) Sleep, (c) Addictions, (d) Suicide, and (e) Nutrition. There was limited variability over time and place with regard to the most frequently addressed themes.

Discussion

Despite our focus on journals that specifically address psychological and social aspects of gerontology, the biomedicalization of the field is evident. The somewhat limited variability of themes over time and place is disconcerting as it potentially attests to slow progress and limited attention to contextual/societal variations.
Tomographic filtering via the generalized inverse: a way to account for seismic data uncertainty
Authors: Freissler Roman , Zaroli Christophe , Lambotte Sophie , Schuberth Bernhard S A
Published: May 2020

Tomographic-geodynamic model comparisons are a key component in studies of the present-day state and evolution of Earth’s mantle. To account for the limited seismic resolution, ‘tomographic filtering’ of the geodynamically predicted mantle structures is a standard processing step in this context. The filtered model provides valuable information on how heterogeneities are smeared and modified in amplitude given the available seismic data and underlying inversion strategy. An important aspect that has so far not been taken into account are the effects of data uncertainties. We present a new method for ‘tomographic filtering’ in which it is possible to include the effects of random and systematic errors in the seismic measurements and to analyse the associated uncertainties in the tomographic model space. The ‘imaged’ model is constructed by computing the generalized-inverse projection (GIP) of synthetic data calculated in an earth model of choice. An advantage of this approach is that a reparametrization onto the tomographic grid can be avoided, depending on how the synthetic data are calculated. To demonstrate the viability of the method, we compute traveltimes in an existing mantle circulation model (MCM), add specific realizations of random seismic ‘noise’ to the synthetic data and apply the generalized inverse operator of a recent Backus–Gilbert-type global S-wave tomography. GIP models based on different noise realizations show a significant variability of the shape and amplitude of seismic anomalies. This highlights the importance of interpreting tomographic images in a prudent and cautious manner. Systematic errors, such as event mislocation or imperfect crustal corrections, can be investigated by introducing an additional term to the noise component so that the resulting noise distributions are biased. In contrast to Gaussian zero-mean noise, this leads to a bias in model space; that is, the mean of all GIP realizations also is non-zero. Knowledge of the statistical properties of model uncertainties together with tomographic resolution is crucial for obtaining meaningful estimates of Earth’s present-day thermodynamic state. A practicable treatment of error propagation and uncertainty quantification will therefore be increasingly important, especially in view of geodynamic inversions that aim at ‘retrodicting’ past mantle evolution based on tomographic images.
3-D joint geodetic and strong-motion finite fault inversion of the 2008 May 12, Wenchuan, China Earthquake
Authors: Ramirez-Guzman Leonardo , Hartzell Stephen
Published: May 2020

We present a source inversion of the 2008 Wenchuan, China earthquake, using strong-motion waveforms and geodetic offsets together with 3-D synthetic ground motions. We applied the linear multiple time window technique considering geodetic and dynamic Green's functions computed with the finite-element method and the reciprocity and Strain Green's Tensor formalism. All ground motion estimates, valid up to 1 Hz, accounted for 3-D effects, including the topography and the geometry of the Beichuan and Pengguan faults. Our joint inversion has a higher moment (M0) than a purely geodetic inversion and the slip distribution presents differences when compared to 1-D model source inversions. The moment is estimated to be M0 = 1.2 × 1021 N·m, slightly larger than other works. Our results show that considering a complex 3-D structure reduces the size of large areas of 10 m slip or greater by distributing it in wider zones, with reduced slips, in the central portion of the Beichuan and the Pengguan faults. Finally, we compare our source with a relocated aftershock catalogue and conclude that the 4–5 m slip contours approximately bound the absence or presence of aftershocks.
Management of Acute Severe Ulcerative Colitis in a Pregnant Woman With COVID-19 Infection: A Case Report and Review of the Literature
Authors: Rosen Melissa H , Axelrad Jordan , Hudesman David , Rubin David T , Chang Shannon
Published: May 2020

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.
Dwork Crystals II
Authors: Beukers Frits , Vlasenko Masha
Published: May 2020

We give a generalization of $p$-adic congruences for truncated period functions that were originally discovered for a class of hypergeometric functions by Bernard Dwork.
Green Functions for the Pressure of Stokes Systems
Authors: Choi Jongkeun , Dong Hongjie
Published: May 2020

We study Green functions for the pressure of stationary Stokes systems in a (possibly unbounded) domain $\Omega \subset \mathbb{R}^d$, where $d\ge 2$. We construct the Green function when coefficients are merely measurable in one direction and have Dini mean oscillation in the other directions and $\Omega $ is such that the divergence equation is solvable there. We also establish global pointwise bounds for the Green function and its derivatives when coefficients have Dini mean oscillation and $\Omega $ has a $C^{1,\textrm{Dini}}$ boundary. Green functions for the flow velocity of Stokes systems are also considered.
Effect of Interleukin-36β on Activating Autophagy of CD4+CD25+ Regulatory T cells and Its Immune Regulation in Sepsis
Authors: Ge Yun , Huang Man , Dong Ning , Yao Yong-ming
Published: May 2020

Background

CD4+CD25+ regulatory T cells (Tregs) play an essential role in sepsis-induced immunosuppression. How, the effects of interleukin 36 (IL-36) cytokines on CD4+CD25+ Tregs and their underlying mechanism(s) in sepsis remain unknown.

Methods

Our study was designed to investigate the impacts of IL-36 cytokines on murine CD4+CD25+ Tregs in presence of lipopolysaccharide (LPS) and in a mouse model of sepsis induced by cecal ligation and puncture (CLP). IL-36–activated autophagy was evaluated by autophagy markers, autophagosome formation, and autophagic flux.

Results

IL-36α, IL-36β, and IL-36γ were expressed in murine CD4+CD25+ Tregs. Stimulation of CD4+CD25+ Tregs with LPS markedly up-regulated the expression of these cytokines, particularly IL-36β. IL-36β strongly suppressed CD4+CD25+ Tregs under LPS stimulation and in septic mice challenged with CLP, resulting in the amplification of T-helper 1 response and the proliferation of effector T cells. Mechanistic studies revealed that IL-36β triggered autophagy of CD4+CD25+ Tregs. These effects were significantly attenuated in the presence of the autophagy inhibitor 3-methyladenine or Beclin1 knockdown. In addition, early IL-36β administration reduced the mortality rate in mice subjected to CLP. Depletion of CD4+CD25+ Tregs before the onset of sepsis obviously abrogated IL-36β–mediated protection against sepsis.

Conclusions

These findings suggest that IL-36β diminishes the immunosuppressive activity of CD4+CD25+ Tregs by activating the autophagic process, thereby contributing to improvement of the host immune response and prognosis in sepsis.
Towards personalized guidelines: using machine-learning algorithms to guide antimicrobial selection
Authors: Moran Ed , Robinson Esther , Green Christopher , Keeling Matt , Collyer Benjamin
Published: May 2020

Background

Electronic decision support systems could reduce the use of inappropriate or ineffective empirical antibiotics. We assessed the accuracy of an open-source machine-learning algorithm trained in predicting antibiotic resistance for three Gram-negative bacterial species isolated from patients’ blood and urine within 48 h of hospital admission.

Methods

This retrospective, observational study used routine clinical information collected between January 2010 and October 2016 in Birmingham, UK. Patients from whose blood or urine cultures Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa was isolated were identified. Their demographic, microbiology and prescribing data were used to train an open-source machine-learning algorithm—XGBoost—in predicting resistance to co-amoxiclav and piperacillin/tazobactam. Multivariate analysis was performed to identify predictors of resistance and create a point-scoring tool. The performance of both methods was compared with that of the original prescribers.

Results

There were 15 695 admissions. The AUC of the receiver operating characteristic curve for the point-scoring tools ranged from 0.61 to 0.67, and performed no better than medical staff in the selection of appropriate antibiotics. The machine-learning system performed statistically but marginally better (AUC 0.70) and could have reduced the use of unnecessary broad-spectrum antibiotics by as much as 40% among those given co-amoxiclav, piperacillin/tazobactam or carbapenems. A validation study is required.

Conclusions

Machine-learning algorithms have the potential to help clinicians predict antimicrobial resistance in patients found to have a Gram-negative infection of blood or urine. Prospective studies are required to assess performance in an unselected patient cohort, understand the acceptability of such systems to clinicians and patients, and assess the impact on patient outcome.
Linezolid-resistant (Tn6246::fexB-poxtA) Enterococcus faecium strains colonizing humans and bovines on different continents: similarity without epidemiological link
Authors: Freitas Ana R , Tedim Ana P , Duarte Bárbara , Elghaieb Houyem , Abbassi Mohamed S , Hassen Abdennaceur , Read Antónia , Alves Valquíria , Novais Carla , Peixe Luísa
Published: May 2020

Objectives

poxtA is the most recently described gene conferring acquired resistance to linezolid, a relevant antibiotic for treating enterococcal infections. We retrospectively screened for poxtA in diverse enterococci and aimed to characterize its genetic/genomic contexts.

Methods

poxtA was screened by PCR in 812 enterococci from 458 samples (hospitals/healthy humans/wastewater/animals/retail food) obtained in Portugal/Angola/Tunisia (1996–2019). Antimicrobial susceptibility testing was performed for 13 antibiotics (EUCAST/CLSI). poxtA stability (∼500 generations), transfer (filter mating), clonality (SmaI-PFGE) and location (S1-PFGE/hybridization) were tested. WGS (Illumina-HiSeq) was performed for clonal representatives.

Results

poxtA was detected in Enterococcus faecium from six samples (1.3%): a healthy human (rectal swab) in Porto, Portugal (ST32/2001); four farm cows (milk) in Mateur, Tunisia (ST1058/2015); and a hospitalized patient (faeces) in Matosinhos, Portugal (ST1058/2015). All expressed resistance to linezolid (MIC = 8 mg/L), chloramphenicol, tetracycline and erythromycin, with variable resistance to ciprofloxacin and streptomycin. ST1058-poxtA-carrying isolates from Tunisia and Portugal differed by two SNPs and had similar plasmid content. poxtA, located in an IS1216-flanked Tn6246-like element, co-hybridized with fexB on one or more plasmids per isolate (one to three plasmids of 30–100 kb), was stable after several generations and transferred only from ST1058. ST1058 strains carried resistance/virulence genes (Efmqnr/acm) possibly induced under selective quinolone treatment.

Conclusions

poxtA has been circulating in Portugal since at least 2001, corresponding to the oldest description worldwide to date. We also extend the reservoir of poxtA to bovines. The similar linezolid-resistant poxtA-carrying strains colonizing humans and livestock on different continents, and without a noticeable relationship, suggests a recent transmission event or convergent evolution of E. faecium populations in different hosts and geographic regions.
Understanding enterprise data warehouses to support clinical and translational research
Authors: Campion Thomas R , Craven Catherine K , Dorr David A , Knosp Boyd M
Published: May 2020

Objective

Among National Institutes of Health Clinical and Translational Science Award (CTSA) hubs, adoption of electronic data warehouses for research (EDW4R) containing data from electronic health record systems is nearly ubiquitous. Although benefits of EDW4R include more effective, efficient support of scientists, little is known about how CTSA hubs have implemented EDW4R services. The goal of this qualitative study was to understand the ways in which CTSA hubs have operationalized EDW4R to support clinical and translational researchers.

Materials and Methods

After conducting semistructured interviews with informatics leaders from 20 CTSA hubs, we performed a directed content analysis of interview notes informed by naturalistic inquiry.

Results

We identified 12 themes: organization and data; oversight and governance; data access request process; data access modalities; data access for users with different skill sets; engagement, communication, and literacy; service management coordinated with enterprise information technology; service management coordinated within a CTSA hub; service management coordinated between informatics and biostatistics; funding approaches; performance metrics; and future trends and current technology challenges.

Discussion

This study is a step in developing an improved understanding and creating a common vocabulary about EDW4R operations across institutions. Findings indicate an opportunity for establishing best practices for EDW4R operations in academic medicine. Such guidance could reduce the costs associated with developing an EDW4R by establishing a clear roadmap and maturity path for institutions to follow.

Conclusions

CTSA hubs described varying approaches to EDW4R operations that may assist other institutions in better serving investigators with electronic patient data.