bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable selection in microbiome compositional data analysis
Authors: Susin Antoni , Wang Yiwen , Lê Cao Kim-Anh , Calle M Luz
Published: May 2020

Though variable selection is one of the most relevant tasks in microbiome analysis, e.g. for the identification of microbial signatures, many studies still rely on methods that ignore the compositional nature of microbiome data. The applicability of compositional data analysis methods has been hampered by the availability of software and the difficulty in interpreting their results. This work is focused on three methods for variable selection that acknowledge the compositional structure of microbiome data: selbal, a forward selection approach for the identification of compositional balances, and clr-lasso and coda-lasso, two penalized regression models for compositional data analysis. This study highlights the link between these methods and brings out some limitations of the centered log-ratio transformation for variable selection. In particular, the fact that it is not subcompositionally consistent makes the microbial signatures obtained from clr-lasso not readily transferable. Coda-lasso is computationally efficient and suitable when the focus is the identification of the most associated microbial taxa. Selbal stands out when the goal is to obtain a parsimonious model with optimal prediction performance, but it is computationally greedy. We provide a reproducible vignette for the application of these methods that will enable researchers to fully leverage their potential in microbiome studies.
Comparative performance of the BGI and Illumina sequencing technology for single-cell RNA-sequencing
Authors: Senabouth Anne , Andersen Stacey , Shi Qianyu , Shi Lei , Jiang Feng , Zhang Wenwei , Wing Kristof , Daniszewski Maciej , Lukowski Samuel W , Hung Sandy S C , Nguyen Quan , Fink Lynn , Beckhouse Anthony , Pébay Alice , Hewitt Alex W , Powell Joseph E
Published: May 2020

The libraries generated by high-throughput single cell RNA-sequencing (scRNA-seq) platforms such as the Chromium from 10× Genomics require considerable amounts of sequencing, typically due to the large number of cells. The ability to use these data to address biological questions is directly impacted by the quality of the sequence data. Here we have compared the performance of the Illumina NextSeq 500 and NovaSeq 6000 against the BGI MGISEQ-2000 platform using identical Single Cell 3′ libraries consisting of over 70 000 cells generated on the 10× Genomics Chromium platform. Our results demonstrate a highly comparable performance between the NovaSeq 6000 and MGISEQ-2000 in sequencing quality, and the detection of genes, cell barcodes, Unique Molecular Identifiers. The performance of the NextSeq 500 was also similarly comparable to the MGISEQ-2000 based on the same metrics. Data generated by both sequencing platforms yielded similar analytical outcomes for general single-cell analysis. The performance of the NextSeq 500 and MGISEQ-2000 were also comparable for the deconvolution of multiplexed cell pools via variant calling, and detection of guide RNA (gRNA) from a pooled CRISPR single-cell screen. Our study provides a benchmark for high-capacity sequencing platforms applied to high-throughput scRNA-seq libraries.
Systemic Unfairness, Access to Justice and Futility: A Framework
Authors: Adams-Prassl Abi , Adams-Prassl Jeremias
Published: May 2020

This article develops a conceptual framework for access to justice as a ground of judicial review in English law. We identify a hitherto undertheorised strand of cases which enable courts to review policy within proper constitutional bounds: the doctrine of systemic unfairness, which focuses on risks inherent in a system as a whole. In the context of access to justice, the relevant systemic risk is one of futility: a rational litigant’s inability to vindicate a meritorious claim. Proving the required facts in the context of judicial review proceedings is not an easy task. Litigants must look beyond the realisation of harm to the mechanisms which put access to justice at risk. It is only where the combined impact or cost of system-level risk is particularly severe that a policy-level challenge will succeed on access to justice grounds.
Health Equity’s Missing Substance: (Re)Engaging the Normative in Public Health Discourse and Knowledge Making
Authors: Wildgen Adam , Denny Keith
Published: May 2020

Since 1984, the idea of health equity has proliferated throughout public health discourse with little mainstream critique for its variability and distance from its original articulation signifying social transformation and a commitment to social justice. In the years since health equity’s emergence and proliferation, it has taken on a seemingly endless range of invocations and deployments, but it most often translates into proactive and apolitical discourse and practice. In Margaret Whitehead’s influential characterization (1991), achieving health equity requires determining what is inequitable by examining and judging the causes of inequalities in the context of what is going on in the rest of society. However, it also remains unclear how or if public health actors examine and judge the causes of health inequality. In this article, we take the concept of health equity itself as an object of study and consider the ways in which its widespread deployment has entailed a considerable emptying of its semantic and political content. We point toward equity’s own discursive productivity as well as the quantifying imperative embedded within evidentiary norms that govern knowledge making, and performance management regimes that govern public health practices. Under current conditions of knowledge making and performance evaluation, a range of legitimate action and inaction is produced at the same time that more socially transformative action is legitimately curtailed—not merely by politics, but by the rules of the field in which public health actors work. Ultimately, meaningful progress on a normative ethical idea like health equity will require both substantial philosophical content and an analysis of what is going on in the rest of society.
Response to lower dose TNF inhibitors in axial spondyloarthritis; a real-world multicentre observational study
Authors: Van Rossen Liz , Chan Antoni , Gilbert Annie , Gaffney Karl , Harris Claire , Machado Pedro M , Santos Liliana R , Sengupta Raj , Basset Paul , Keat Andrew
Published: May 2020

Objective

Dose optimization of TNF inhibitors in axial spondyloarthritis (axSpA) is attractive, but it is unclear for which patients this approach might be appropriate.

Methods

Seventy-one patients with axSpA, from six UK centres, were identified who had reduced their dose of TNF inhibitor after being considered to be stable responders. All completed a questionnaire concerning their approach to and experience of dose reduction. Data on patient characteristics, metrology and CRP were retrieved retrospectively from patient records.

Results

Over 2 years of observation, 60 (84.5%) remained (REM) on reduced-dose medication and 11 (15.5%) reverted (REV) to the original dose. The overall mean dose reduction was 39% for REM patients and 44% for REV patients. Both groups initially responded in a similar manner to treatment, but the data showed a trend that younger women were more likely to revert. Neither BMI nor smoking was associated with continued low-dose responsiveness. Eight of the 11 REV patients reverted by 6 months. None reached criteria of secondary drug failure, and all regained control after increasing back to the original dose. Most patients in both groups reached the decision to reduce the dose jointly with clinicians. A preference for taking the reduced dose was not associated with low-dose drug survival.

Conclusion

Many patients with axSpA remain well symptomatically after stepping down the dose of TNF inhibitor, but young women are less likely to do well on a reduced dose. Dose reduction should be one element of the management of patients with axSpA.
Monetary Policy and Corporate Bond Returns
Authors: Guo Haifeng , Kontonikas Alexandros , Maio Paulo
Published: May 2020

We investigate the impact of monetary policy shocks on excess corporate bonds returns. We obtain a significant negative response of bond returns to policy shocks, which is especially strong among low-grading bonds. The largest portion of this response is related to higher expected bond returns (risk premium news), while the impact on expectations of future interest rates (interest rate news) plays a secondary role. However, the interest rate channel is dominant among high-grading bonds and Treasury bonds. Looking at the two components of bond premium news, we find that the dominant channel for high-rating (low-rating) bonds is term premium (credit premium) news. (JEL 44, E52, G10, G12)

Received: March 25, 2019: Editorial decision: March 27, 2020 by Editor: Hui Chen. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Genetic Susceptibility to Clozapine-Induced Agranulocytosis/Neutropenia Across Ethnicities: Results From a New Cohort of Turkish and Other Caucasian Participants, and Meta-Analysis
Authors: Okhuijsen-Pfeifer Cynthia , Ayhan Yavuz , Lin Bochao D , van Eijk Kristel R , Bekema Erwin , Kool Lindy J G B , Bogers Jan P A M , Muderrisoglu Ahmet , Babaoglu Melih O , Van Assche Evelien , Medic Jelena , Veerman Selene , Cohen Dan , van Beek Hanneke , de Jonge Annemieke A M , Beld Edwin ,   PAT Clozapine Associated Leukopenia/Agranulocytosis Study Group, Yağcıoğlu A Elif Anıl , Luykx Jurjen J , Yoca Gökhan , Altınyazar Vesile , Aydın Memduha , Görgülü Yasemin , Kıvırcık Akdede Berna B , Alptekin Köksal , Üçok Alp , Danacı Ayşen Esen , İlhan Bilge Çetin , Ulusoy Semra , Soygür Haldun , Özdemir Hatice , Çelik Mustafa , Orhan Fatma Özlem , Ozan Hasret , Kaygısız İsmet
Published: May 2020

Clozapine (CLZ) is considered the most effective antipsychotic, but its use is associated with neutropenia (CIN) and agranulocytosis (CIA). Although the exact etiology of these hazardous side effects is unknown, 4 genetic polymorphisms have been implicated by genome-wide association studies (GWAS), mostly performed in North-Western Europeans. These polymorphisms are rs113332494 (HLA-DQB1), rs41549217 (HLA-B), and rs1546308/rs149104283 (SLCO1B3/7), several of which were not directly genotyped but imputed. To test whether these 4 single-nucleotide polymorphisms (SNPs) are associated with CIN/CIA in a Turkish population and in a more extensive group of Caucasians, we directly genotyped these polymorphisms using Taqman and Sanger sequencing and performed logistic regression. We divided our participants (234 CLZ-using participants of whom 31 CIN/CIA cases) into (1) North-Western European, (2) Turkish, (3) Caucasian (=1 + 2); and (4) a total group (Caucasian + other ethnicities). Rs113332494 (HLA-DQB1) was significantly associated with CIN/CIA in the total group (P = 3.5 × 10−8), in the Caucasian group (P = 9.3 × 10−6) and in the Turkish group (P = 2.8 × 10−5). Rs41549217 (HLA-B) was nominally significant in the Caucasian group (P = .018). In meta-analysis of our results and the previously reported genome-wide results, 3 SNPs were significantly associated with CIN/CIA in participants with Caucasian ancestry: rs113332494 (P = 2.05 × 10−8), rs41549217 (P = 7.19 × 10−9), and rs149104283 (P = 5.54 × 10−9), with the result for rs1546308 (SCLO1B3/SCLO1B7) being significantly heterogeneous across studies. Our results hint at ethnicity-dependent and clinically relevant effects of genetic polymorphisms on the risk to develop CIN/CIA. Pharmacogenetic testing can complement clinical decision making and thus empower appropriate CLZ prescribing, but ancestry should be taken into account when performing such testing for CLZ.
Attitudes toward Refugees in Contemporary Europe: A Longitudinal Perspective on Cross-National Differences
Authors: Czymara Christian S
Published: May 2020

In 2015, the number of people seeking asylum in Europe skyrocketed. However, asylum applications were mainly concentrated in a few destination countries such as Germany, Austria, or Sweden. After the so-called EU-Turkey deal, asylum rates quickly dropped in subsequent years. I examine how these developments affected public opinion from both a static and a dynamic comparative perspective. The rapid and largely unpredicted rise in refugee numbers and their prominence in public debates make demographic changes potent drivers of out-group hostility. The analysis of data from over 50,000 individuals in 22 countries contained in the seventh and eighth waves of the European Social Survey shows that attitudes toward refugees do not simply follow trends in asylum applications. Significantly lowering refugee numbers, hence, did not counter anti-refugee sentiments in the European public. Based on intra-country variation over time, the model rather predicts an increase in negative attitudes during times of considerable demographic shifts. Deeper analyses reveal that this effect is stronger for conservative Europeans as well as for those who distrust EU-politics. Moreover, while a general willingness to help is associated with more openness toward refugees, actually experiencing foreigner inflow diminishes this link, suggesting limitations of humanitarian concerns. Results are stable across various modelling and sample choices and not driven by individual countries. In sum, these findings demonstrate the importance of temporal dynamics for the formation of attitudes toward refugees in contemporary Europe and point to potentially polarizing effects of immigration along ideological lines.
Keep America Christian (and White): Christian Nationalism, Fear of Ethnoracial Outsiders, and Intention to Vote for Donald Trump in the 2020 Presidential Election
Authors: Baker Joseph O , Perry Samuel L , Whitehead Andrew L
Published: May 2020

Some of the strongest predictors of voting for Donald Trump in the 2016 presidential election were Christian nationalism and antipathy toward Muslims and immigrants. We examine the interrelated influence of these three factors on Americans’ intentions to vote for Trump in 2020. Consistent with previous research, Christian nationalism and Islamophobia remained strong and significant predictors of intention to vote for Trump; however, the effect of xenophobia was stronger. Further, xenophobia and Islamophobia significantly and substantially mediated the effects of Christian nationalism. Consequently, though Christian nationalism remains theoretically and empirically distinct as a cultural framework, its influence on intending to vote for Trump in 2020 is intimately connected to fears about ethnoracial outsiders. In the penultimate year before Trump’s reelection campaign, the strongest predictors of supporting Trump, in order of magnitude, were political party, xenophobia, identifying as African American (negative), political ideology, Christian nationalism, and Islamophobia.
Is there an Intrinsic Relationship between LFP Beta Oscillation Amplitude and Firing Rate of Individual Neurons in Macaque Motor Cortex?
Authors: Confais Joachim , Malfait Nicole , Brochier Thomas , Riehle Alexa , Kilavik Bjørg Elisabeth
Published: May 2020

The properties of motor cortical local field potential (LFP) beta oscillations have been extensively studied. Their relationship to the local neuronal spiking activity was also addressed. Yet, whether there is an intrinsic relationship between the amplitude of beta oscillations and the firing rate of individual neurons remains controversial. Some studies suggest a mapping of spike rate onto beta amplitude, while others find no systematic relationship. To help resolve this controversy, we quantified in macaque motor cortex the correlation between beta amplitude and neuronal spike count during visuomotor behavior. First, in an analysis termed “task-related correlation”, single-trial data obtained across all trial epochs were included. These correlations were significant in up to 32% of cases and often strong. However, a trial-shuffling control analysis recombining beta amplitudes and spike counts from different trials revealed these task-related correlations to reflect systematic, yet independent, modulations of the 2 signals with the task. Second, in an analysis termed “trial-by-trial correlation”, only data from fixed trial epochs were included, and correlations were calculated across trials. Trial-by-trial correlations were weak and rarely significant. We conclude that there is no intrinsic relationship between the firing rate of individual neurons and LFP beta oscillation amplitude in macaque motor cortex.
Blinded, Multicenter Evaluation of Drug-induced Changes in Contractility Using Human-induced Pluripotent Stem Cell-derived Cardiomyocytes
Authors: Saleem Umber , van Meer Berend J , Katili Puspita A , Mohd Yusof Nurul A N , Mannhardt Ingra , Garcia Ana Krotenberg , Tertoolen Leon , de Korte Tessa , Vlaming Maria L H , McGlynn Karen , Nebel Jessica , Bahinski Anthony , Harris Kate , Rossman Eric , Xu Xiaoping , Burton Francis L , Smith Godfrey L , Clements Peter , Mummery Christine L , Eschenhagen Thomas , Hansen Arne , Denning Chris
Published: May 2020

Animal models are 78% accurate in determining whether drugs will alter contractility of the human heart. To evaluate the suitability of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for predictive safety pharmacology, we quantified changes in contractility, voltage, and/or Ca2+ handling in 2D monolayers or 3D engineered heart tissues (EHTs). Protocols were unified via a drug training set, allowing subsequent blinded multicenter evaluation of drugs with known positive, negative, or neutral inotropic effects. Accuracy ranged from 44% to 85% across the platform-cell configurations, indicating the need to refine test conditions. This was achieved by adopting approaches to reduce signal-to-noise ratio, reduce spontaneous beat rate to ≤ 1 Hz or enable chronic testing, improving accuracy to 85% for monolayers and 93% for EHTs. Contraction amplitude was a good predictor of negative inotropes across all the platform-cell configurations and of positive inotropes in the 3D EHTs. Although contraction- and relaxation-time provided confirmatory readouts forpositive inotropes in 3D EHTs, these parameters typically served as the primary source of predictivity in 2D. The reliance of these “secondary” parameters to inotropy in the 2D systems was not automatically intuitive and may be a quirk of hiPSC-CMs, hence require adaptations in interpreting the data from this model system. Of the platform-cell configurations, responses in EHTs aligned most closely to the free therapeutic plasma concentration. This study adds to the notion that hiPSC-CMs could add value to drug safety evaluation.
Biotransformation Capacity of Zebrafish (Danio rerio) Early Life Stages: Functionality of the Mercapturic Acid Pathway
Authors: Tierbach Alena , Groh Ksenia J , Schönenberger René , Schirmer Kristin , Suter Marc J -F
Published: May 2020

Zebrafish (Danio rerio) early life stages offer a versatile model system to study the efficacy and safety of drugs or other chemicals with regard to human and environmental health. This is because, aside from the well-characterized genome of zebrafish and the availability of a broad range of experimental and computational research tools, they are exceptionally well suited for high-throughput approaches. Yet, one important pharmacokinetic aspect is thus far only poorly understood in zebrafish embryo and early larvae: their biotransformation capacity. Especially, biotransformation of electrophilic compounds is a critical pathway because they easily react with nucleophile molecules, such as DNA or proteins, potentially inducing adverse health effects. To combat such adverse effects, conjugation reactions with glutathione and further processing within the mercapturic acid pathway have evolved. We here explore the functionality of this pathway in zebrafish early life stages using a reference substrate (1-chloro-2,4-dinitrobenzene, CDNB). With this work, we show that zebrafish embryos can biotransform CDNB to the respective glutathione conjugate as early as 4 h postfertilization. At all examined life stages, the glutathione conjugate is further biotransformed to the last metabolite of the mercapturic acid pathway, the mercapturate, which is slowly excreted. Being able to biotransform electrophiles within the mercapturic acid pathway shows that zebrafish early life stages possess the potential to process xenobiotic compounds through glutathione conjugation and the formation of mercapturates. The presence of this chemical biotransformation and clearance route in zebrafish early life stages supports the application of this model in toxicology and chemical hazard assessment.
Lead Impairs the Development of Innate Lymphoid Cells by Impeding the Differentiation of Their Progenitors
Authors: Zhu Tingting , Zhao Yifan , Zhang Peng , Shao Yiming , He Jinyi , Xue Peng , Zheng Weiwei , Qu Weidong , Jia Xiaodong , Zhou Zhijun , Lu Rongzhu , He Miao , Zhang Yubin
Published: May 2020

Lead (Pb) is a heavy metal toxic to the immune system, yet the influence of Pb on innate lymphoid cells (ILC) remains to be defined. In this study, we found that occupationally relevant level of Pb exposure impaired ILC development at the progenitor level by activating Janus Kinase1. C57BL/6 mice treated with 1250 ppm, but not 125 ppm Pb acetic via drinking water for 8 weeks had reduced number of mature ILC, which was not caused by increased apoptosis or suppressed proliferation. Conversely, Pb increased the number of innate lymphoid cell progenitors (ILCP) in the bone marrow. The discordant observation indicated that an obstruction of ILCP differentiation into mature ILC during Pb exposure existed. Pb directly acted on ILCP to suppress their proliferation, indicating that ILCP were less activated during Pb exposure. Reciprocal ILCP transplantation assay confirmed that Pb impeded the differentiation of ILCP into mature ILC, as ILCP gave rise to fewer mature ILC in Pb-treated recipients compared with control recipients. In vitro assays suggested that the obstruction of ILCP differentiation by Pb exposure was due to increased activation of Janus Kinase1. Thus, Pb impeded ILCP differentiation into mature ILC to result in an accumulation of ILCP in the bone marrow and the resultant decreased number of mature ILC in lymphoid and nonlymphoid tissues in mice. Moreover, by analyses of ILC and ILCP in peripheral blood mononuclear cells of human subjects occupationally exposed to Pb, we revealed that Pb might also impede the development of ILC in human.
Comparative Genomics, Pangenome, and Phylogenomic Analyses of Brenneria spp., and Delineation of Brenneria izadpanahii sp. nov.
Authors: Bakhshi ganje Meysam , Mackay John , Nicolaisen Mogens , Shams-Bakhsh Masoud
Published: May 2020

Brenneria species are bacterial plant pathogens mainly affecting woody plants. Association of all members with devastating disorders (e.g., acute oak decline in Iran and United Kingdom) are due to adaptation and pathogenic behavior in response to host and environmental factors. Some species, including B. goodwinii, B. salicis, and B. nigrifluens, also show endophytic residence. Here we show that all species including novel Brenneria sp. are closely related. Gene-based and genome/pangenome-based phylogeny divide the genus into two distinct lineages, Brenneria clades A and B. The two clades were functionally distinct and were consistent with their common and special potential activities as determined via annotation of functional domains. Pangenome analysis demonstrated that the core pathogenicity factors were highly conserved, an hrp gene cluster encoding a type III secretion system was found in all species except B. corticis. An extensive repertoire of candidate virulence factors was identified. Comparative genomics indicated a repertoire of plant cell wall degrading enzymes, metabolites/antibiotics, and numerous prophages providing new insights into Brenneria−host interactions and appropriate targets for further characterization. This work not only documented the genetic differentiation of Brenneria species but also delineates a more functionally driven understanding of Brenneria by comparison with relevant Pectobacteriaceae thereby substantially enriching the extent of information available for functional genomic investigations.
The Effectiveness of Ego State Therapy in the Reduction of Athletes’ Stress Levels
Authors: Sin Tjung Hauw , Ifdil Ifdil , Amalianita Berru
Published: May 2020

Stress affects the performance level of professional athletes during training and competition, thereby decreasing their achievements. Using an individual approach, this study aimed to analyze ego state therapy to reduce stress through relaxation. A single-subject design was used to obtain data from 6 athletes with high stress through observation and administration of the Mini Stress Scale. The result showed that this therapy acts as an alternative treatment in reducing stress.
Dexmedetomidine Activation of Dopamine Neurons in the Ventral Tegmental Area Attenuates the Depth of Sedation in Mice
Authors: Qiu Gaolin , Wu Ying , Yang Zeyong , Li Long , Zhu Xiaona , Wang Yiqiao , Sun Wenzhi , Dong Hailong , Li Yuanhai , Hu Ji
Published: May 2020

Background

Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine.

Methods

Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca2+ indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography.

Results

Ca2+ signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, –0.745 [–1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, –0.498 [–0.664; –0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, –0.329 [–1.220; –0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 μg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice).

Conclusions

Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Attending Physician's Attitudes Toward Podcasting as a Source of Medical Education: An Exploratory Study
Authors: Tarchichi Tony R. , Szymusiak John
Published: May 2020

Introduction:

People are increasingly consuming information on-demand. Podcasting is a growing medium for education in an on-demand world. There is a paucity of data on podcasting as a means of continuing medical education (CME) for attending physicians.

Methods:

The authors performed an exploratory survey of a convenience sample of listeners to a Pediatric Hospital Medicine podcast to learn about their attitudes regarding podcasting. A 17-question survey consisting of demographic data, attitudinal questions, and qualitative questions was administered electronically in February 2018.

Results:

At the time of the survey, the 12 podcast episodes were downloaded 17,288 times, with 162 CME credits being issued. Of 129 respondents, 75.2% were attendings. The majority agreed the podcast was of “high educational value” and was of equal or better educational value as medical journals or national conferences. Qualitative content analysis revealed listeners valued the convenience of the podcast, and community-based hospitalists felt the podcast connected them to the broader hospitalist community.

Discussion:

Our respondents found podcasting to be a beneficial and convenient learning method. The ability to apply for CME credit was not a major motivation for listening. Further research is needed to investigate more objective outcomes and assess attitudes of a random sampling of physicians as opposed to a self-selected sample.
One Hospital's Call to Action: Preparing Faculty for a New Medical School
Authors: Nonaillada Jeannine
Published: May 2020

Introduction:

This is a single-site feasibility project where a new, 3-year medical school was created. To respond to emergent teaching preparedness and leadership readiness in new administrative roles, an educational series taught by clinical faculty and staff was offered at noontime.

Methods:

The series focused on administrative skills, teaching techniques, and student success. The curricular strategies employed were the menu approach for educational offerings and spiral sequencing of curricula. Faculty teaching preparedness and leadership readiness were measured by an electronic questionnaire devised by the author and contributors of this article. Descriptive statistics were conducted for outcomes.

Results:

Findings indicate noontime education using a menu approach of listed offerings and curricular themes spiraled was a feasible faculty development method for teaching preparedness and leadership readiness for new administrative roles. Specifically, faculty reported increased use of active learning strategies after attending the noontime educational series.

Conclusions:

Next steps include longitudinal follow-up with our faculty participants to measure retention and sustainability of our findings, as well as additional instructional strategies that we could incorporate into future educational sessions.
Anti-PD-1 induced collagenous colitis in metastatic melanoma: a rare severe adverse event
Authors: Janela-Lapert Raphaël , Bouteiller Julie , Deschamps-Huvier Aurélie , Duval-Modeste Anne-Bénédicte , Joly Pascal
Published: May 2020

Immunotherapy has improved the overall survival of patients with metastatic melanoma. Inflammatory bowel disease-like colitis is the most frequent gastrointestinal serious adverse event in patients treated with immune-checkpoint inhibitors. Collagenous colitis is microscopic colitis. Only two cases of immune-checkpoint inhibitors induced collagenous colitis have been reported. A man in his early 70s was referred for a metastatic melanoma treated with nivolumab as the fourth line of treatment. During the 21st cycle, the patient complained of watery, nonbloody diarrhea (around six times per day). Rectosigmoidoscopy showed no mucosal lesion. A thickened subepithelial collagen band was evidenced by trichrome staining, which was suggestive of collagenous colitis. Nivolumab was stopped and the patient was treated with budesonide 9 mg/day in combination with loperamide and cholestyramine, leading to improvement of diarrhea. However, worsening of digestive symptoms during tapering of corticosteroid dose required the permanent discontinuation of nivolumab. Due to the very low number of cases reported to date and their different evolution under corticosteroids, it is not clear whether or not immune checkpoint inhibitors can be restarted in these patients.
ACR–ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy
Authors: Chao Samuel T. , Dad Luqman K. , Dawson Laura A. , Desai Neil B. , Pacella Matthew , Rengan Ramesh , Xiao Ying , Yenice Kamil M. , Rosenthal Seth A. , Hartford Alan
Published: May 2020

Aim/Objectives/Background:

To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation.

Methods:

The ACR–ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy was revised according to the process described on the ACR website (“The Process for Developing ACR Practice Parameters and Technical Standards,” www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document.

Results:

Given the complexities of SBRT, a separate document was created to develop a technical standard for the medical physics of SBRT (ACR–AAPM Technical Standard for Medical Physics Performance Monitoring of Stereotactic Body Radiation Therapy). Workflow, qualifications and responsibilities of personnel, specifications, documentation, quality control/safety/improvement, simulation/treatment, and follow-up were addressed in this practice parameter.

Conclusions:

This practice parameter assists practitioners in providing safe and appropriate SBRT treatment and care for patients when clinically indicated. As technologies and techniques continue to evolve, this document will be reviewed, revised and renewed accordingly to a 5 year or sooner timeline specified by the ACR.
End-of-Life Care Provided for Cancer Patients
Authors: Ghezelsefli Zohreh , Ahmadi Fazlollah , Mohammadi Eesa
Published: May 2020

In the health care setting, and especially in cancer patients nearing the end of life, administrators, medical staff, patients, and families face challenges of a social, legal, religious, and cultural nature in the process of care. The present study aimed to perform a metasynthesis of qualitative studies conducted on providing end-of-life care for cancer patients. The present metasynthesis was conducted using Sandelowski and Barroso's method. A literature search was performed in PubMed, Scopus, Web of Science, and Embase databases, from the inception to date, and a total of 21 articles were identified as eligible for inclusion in the study. Critical Appraisal Skills Programme (CASP) criteria were used for assessing the articles, and data were analyzed by the subject review. Six themes were extracted for end-of-life care including psychological support, palliative support, educational-counseling support, spiritual support, preferential support, and supportive interactions, each comprising a number of categories. The most frequently mentioned categories were high-value care (67%) and adaptive acceptance (57%). The findings of this metasynthesis support the view that nurses are moral agents who are deeply invested in the moral integrity of end-of-life care involving assisted death. The present study showed that providing high-value care and facilitating adaptive acceptance are important constituents of a holistic strategy for providing end-of-life care to cancer patients.
Effects of the Continuous Care Model on the Health-Promoting Lifestyle in Breast Cancer Survivors
Authors: Moghaddam Tabrizi Fatemeh , Rajabzadeh Hanieh , Eghtedar Samereh
Published: May 2020

Breast cancer is the most frequently diagnosed cancer and the chief cause of cancer-related death among women worldwide, with the incidence increasing exponentially particularly in low- to middle-income countries. The increase in the incidence of breast cancer is partly accounted for by increases in life expectancy due to improvements in public health, but also related to an increase in risk factors for cancer including smoking, excess body weight, decreased physical activity, and changes in reproductive activity. Health-promoting lifestyle is therefore one of the major topics of importance in studying chronic illnesses and cancer. Health promotion interventions, including the use of care models, have a vast contribution to make in terms of timely diagnosis and improved survival. One such care model, which has been designed to increase self-care, adherence, and performance in chronic patients, is the continuous care model (CCM). This study was conducted with the purpose of determining the influence of the CCM on the health-promoting lifestyle of patients with breast cancer during 2017-2018. In this randomized clinical trial, 60 patients with breast cancer were chosen by convenience sampling followed by random allocation into treatment and control groups. Six sessions of group discussion were held for the treatment group according to the CCM and items in the health-promoting lifestyle questionnaire. Data collection tools included a general health questionnaire, a demographic questionnaire, a family support questionnaire, and the Health Promoting Lifestyle Profile (HPLP), which respondents completed before and after the intervention. P values ≤ .05 were considered significant. When comparing the mean score of health-promoting lifestyle in both the control and treatment groups, before and after the intervention, significant increases in every dimension were observed. The average overall health promotion lifestyle was revealed to be significantly elevated from 123.48 to 147.12. However, in the control group the mean scores had slightly increased or were the same in all the dimensions. In addition, the average overall health promotion lifestyle had increased from 119.89 to 121.32. The observed difference in mean scores was not statistically significant. The CCM increased the score of health-promoting lifestyle of patients with breast cancer. Therefore, this caring model can be considered an alternative to improve healthy lifestyles of patients with cancer.
VISUAL IMPAIRMENT AND MACULAR VASCULAR REMODELING SECONDARY TO RETROGRADE MACULOPATHY IN RETINAL DETACHMENT TREATED WITH SILICON OIL TAMPONADE
Authors: Dormegny Lea , Jeanjean Ludovic C. , Liu Xuanli , Messerlin Arnaud , Bourcier Tristan , Sauer Arnaud , Speeg-Schatz Claude , Gaucher David
Published: May 2020

Purpose:

To assess the frequency of macular cysts (MCs) in retinal detachment treated with silicone oil and evaluate their impact on visual acuity and macular vascularization using optical coherence tomography-angiography.

Methods:

Forty-three eyes of 41 patients treated with silicone oil for retinal detachment were retrospectively studied. Best-corrected visual acuity and 6- × 6-mm optical coherence tomography-angiography examination at least 3 months after silicone oil removal were reviewed. In eyes with MCs, cyst area was measured on the en face optical coherence tomography-angiography image using ImageJ. Density of superficial capillary plexus and area of superficial foveal avascular zone were generated by the optical coherence tomography-angiography. Density of deep capillary plexus and deep foveal avascular zone area were measured using ImageJ.

Results:

Twenty-five eyes (58%) presented with MCs. Cysts were exclusively located in the inner nuclear layer in 60% of cases. Mean best-corrected visual acuity in the MC group was lower than that of the non-MC group (P = 0.012). Macular cyst area negatively correlated with best-corrected visual acuity (P = 0.0201). Density of superficial capillary plexus was higher in the MC group (P < 0.0001), whereas area of superficial foveal avascular zone was lower (P < 0.0001). Macular cyst area negatively correlated with density of deep capillary plexus (P < 0.001).

Conclusion:

The incidence of INL-MCs after silicone oil removal is high. These are associated with impaired vision and macular vascular remodeling. We highlight their similarity with the “retrograde maculopathy” phenomenon.
Self-Made Sleeve for Chandelier Light Simulation
Authors: Kruger Michael , Sommer Michael , Singer Christoph , Seidel Gerald
Published: May 2020

Purpose:

To develop a quick and cost-effective alternative to a chandelier light for vitrectomy.

Methods:

The surgical material available in an ophthalmologic operating room was used to create a sleeve for the vitrectomy light probe and tested on 30 consecutive retinal detachment cases for feasibility.

Results:

A 64 × 5-mm cotton swab stick was cut into the length of the light probe minus the length of the trocar and subsequently pierced by a blunt needle. With this sleeve, the light probe could be safely handled similar to a chandelier light during surgery.

Conclusion:

A sleeve for the light probe can serve as a substitute for a chandelier light during scleral depression in retinal detachment surgery.
Indirect Impact of Ten-valent Pneumococcal Conjugate Vaccine Program on Reducing Antimicrobial Use and Tympanostomy Tube Placements in Finland
Authors: Palmu Arto A. , Rinta-Kokko Hanna , Nohynek Hanna , Nuorti J. Pekka
Published: May 2020

Background:

Acute otitis media (AOM) is the most common reason for antimicrobial use, and tympanostomy tube placement (TTP) is the most common reason for surgery requiring general anesthesia in children. Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in Finland in 2010 for infants. We evaluated the indirect impact of PCV10 on these surrogate otitis outcomes in unvaccinated children.

Methods:

Using before-after design, unvaccinated children ineligible for National Vaccination Program (born January 2006 to May 2010) were followed-up during 2012–2016 (target cohort, age 1.5–7 years). The target cohort was compared with an age- and season-matched unvaccinated reference cohort (born January 2000 to May 2004) during 2006–2010. Antimicrobial purchase data were obtained from the Social Insurance Institution of Finland benefits register. We assessed the relative reduction by generalized Cox regression for outpatient purchases of antibiotics recommended for treatment of AOM in the Finnish guidelines. Data on all TTP procedures were obtained from national hospital discharge register and Social Insurance Institution benefits register.

Results:

The rate of outpatient purchases of antimicrobials recommended for AOM was 51 in the unvaccinated reference cohort and 44/100 person-years in the unvaccinated target cohort; relative rate reduction was 14.7% [95% confidence interval: 14.0–15.3] and absolute rate reduction 7/100 person-years. The rates of TTP in the reference and target cohorts were 1.66/100 and 1.61/100 person-years, respectively. The relative rate reduction was 3.6% (0.7–6.5).

Conclusions:

Antimicrobial use and TTP procedures reduced in unvaccinated children after PCV10 introduction in infants. These indirect effects contribute to the savings in health care resource use for otitis and may also help in combating antimicrobial resistance.
Cat-scratch Disease in the Pediatric Population
Authors: Sandoval Alejandra C. , Reyes Felipe T. , Prado María A. , Peña Anamaría L. , Viviani Tamara N.
Published: May 2020

Background:

Bartonella henselae is the etiologic agent of cat-scratch disease, which affects the entire world population. Due to how poorly characterized the child population is, the objective was to describe the clinical behavior of this disease in children younger than 16 years of age.

Methods:

This was a descriptive study with prospective follow-up of all children younger than 16 years with clinical and serologic diagnoses between 2013 and 2018.

Results:

There were 142 patients; of these, 55.6% had localized disease, 34.5% disseminated with hepatosplenic involvement and 9.8% had atypical disease. The cases of atypical disease were prolonged febrile illness, Parinaud syndrome, subacute bacterial endocarditis/glomerulonephritis and aseptic meningitis. Cervical lymphadenopathy was the most frequent, followed by inguinal adenopathy. There were no differences between the type of manifestation and laboratory values except for a higher erythrocyte sedimentation rate tendency in patients with disseminated and/or atypical disease. The serologic titers throughout were distributed as follows: titer of 1/1024, 71.7%; titer of 1/512, 10.4% and titer of 1/256, 17.9%.

Conclusions:

This is, to our knowledge, the largest series of cat-scratch disease published. We demonstrate that in our environment, the inguinal location is suggestive of this disease, the disseminated presentation, frequent, and that the titers are probably much higher than in other populations, which perhaps indicates the need to re-examine the cut-off point for positivity.
Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial
Authors: Esposito Susanna , Fling John , Chokephaibulkit Kulkanya , de Bruijn Marianne , Oberye Janine , Zhang Bin , Vossen Jeanique , Heijnen Esther , Smolenov Igor
Published: May 2020

Background:

Vaccination against seasonal influenza is recommended for all children with a history of medical conditions placing them at increased risk of influenza-associated complications. The immunogenicity and efficacy of conventional influenza vaccines among young children are suboptimal; one strategy to enhance these is adjuvantation. We present immunogenicity and safety data for an MF59-adjuvanted quadrivalent influenza vaccine (aIIV4) in healthy children and those at a high risk of influenza-associated complications, based on the results of a recently completed phase III study.

Methods:

Children 6 months to 5 years of age (N = 10,644) were enrolled. The study was conducted across northern hemisphere seasons 2013–2014 and 2014–2015. Subjects received either aIIV4 or a nonadjuvanted comparator influenza vaccine. Antibody responses were assessed by hemagglutination inhibition assay against vaccine and heterologous strains. Long-term antibody persistence was assessed (ClinicalTrials.gov: NCT01964989).

Results:

aIIV4 induced significantly higher antibody titers than nonadjuvanted vaccine in high-risk subjects. aIIV4 antibody responses were of similar magnitude in high-risk and healthy subjects. Incidence of solicited local and systemic adverse events (AEs) was slightly higher in aIIV4 than nonadjuvanted vaccinees, in both the healthy and high-risk groups. Incidence of unsolicited AEs, serious AEs and AEs of special interest were similar for adjuvanted and nonadjuvanted vaccinees in the healthy and high-risk groups.

Conclusion:

aIIV4 was more immunogenic than nonadjuvanted vaccine in both the healthy and high-risk study groups. The reactogenicity and safety profiles of aIIV4 and the nonadjuvanted vaccine were acceptable and similar in 6-month- to 5-year-old high-risk and healthy children.