bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial septal defect closure complicated by anomalous inferior vena cava return to the left atrium: a case report of a 5-year-old child
Authors: Tayeh Christelle , El Khoury Maya , Bitar Fadi , Arabi Mariam
Published: May 2019

Background

The anatomy of the sinus venosus atrial septal defect (ASD) of the inferior vena caval type is complex. Limited rate of complications during its closure has been described. One of the unusual complications, with few case reports, is the iatrogenic diversion of the inferior vena cava (IVC) to the left atrium (LA).

Case summary 

We report the case of a 5-year-old boy who underwent previous surgical closure of sinus venosus ASD of the inferior vena caval type aged 2 years. Three years after surgery, he was diagnosed as having iatrogenic diversion of the IVC to the LA.

Discussion 

Cardiologists and cardiac surgeons should be aware of this rare but significant complication following routine ASD surgical repair and vigilant follow-up should be performed routinely.
Purpura fulminans manifesting with Staphylococcus aureus endocarditis: a case report
Authors: Kumar Anirudh , Shah Nishant P , Menon Venu , Nissen Steven E
Published: May 2019

Background

Purpura fulminans (PF) is a haematologic emergency that can occur in the setting of severe septic shock. Its pathophysiology is not well-understood; however, some evidence suggests it may be mediated by excessive protein C consumption.

Case summary

In this case report, we describe a patient with PF secondary to methicillin-resistant Staphylococcus aureus endocarditis. She presented with severe septic shock and, despite haemodynamic improvement, developed a significant purpuric rash. Diagnostic work-up was notable for severely decreased serum levels of protein C. This patient was successfully treated with protein C concentrate and surgical valve replacement.

Discussion

While PF is rarely associated with S. aureus infection, this presentation may be more frequently encountered among clinicians in the current opioid epidemic. Quick recognition is crucial and a multidisciplinary approach, including intravenous infusion of protein C, may be considered.
Impacts of oligodontia on oral health-related quality of life reported by affected children and their parents
Authors: Raziee Leila , Judd Peter , Carmichael Robert , Chen Shiyi , Sidhu Nicole , Suri Sunjay
Published: May 2019

Background

Oligodontia (agenesis of six or more permanent teeth) affects functional, emotional, and social aspects of an individual’s life. Few published studies have evaluated oral health-related quality of life (OHRQoL) in children with oligodontia and very limited have compared the child and parental perceptions.

Methods

Thirty-five 8- to 18-year-old patients with oligodontia (10 M, 25 F; mean age: 12.4 ± 2.9 years; mean number of permanent teeth missing due to agenesis: 8.9 ± 3.2) recruited from The Hospital for Sick Children, Toronto, and Holland Bloorview Kids Rehabilitation Hospital, Toronto, and their parents completed the short format of Child Perception Questionnaire (CPQ11–14) and the Parent Child Perception Questionnaire, respectively.

Results

Children reported significantly worse overall CPQ score than their parents. Correlations between children’s and parents’ overall CPQ score, oral symptoms and functional limitations, and social well-being were not statistically significant. However, as children’s emotional well-being score increased, parents’ score also increased. There was no association between child CPQ score and age, gender, number, and location of permanent tooth agenesis in this sample. There was a significant correlation between overall CPQ score and Site-Specific Tooth Absences.

Conclusion

Children’s overall CPQ score and domain scores were significantly worse than their parents indicating that children with oligodontia had poorer OHRQoL compared to what was perceived by their parents.
Licks, polemics, and the viola bastarda: unity and defiance in Monteverdi’s Fifth Book
Authors: Coluzzi Seth
Published: May 2019

‘Ahi, lasso!’ cry the five voices in Monteverdi’s Cruda Amarilli (1605). The exclamation has long been a central focus of madrigal scholars’ work on Monteverdi’s Fifth Book, and of the debate with Artusi on account of the Canto’s celebrated yet improper dissonances and the controversy they provoked. Little has been said, however, of the unusual bass runs that precede and follow these dissonances, and what these runs (and their divergences from the basso continuo part) might intimate about the larger role of the bass in the madrigal book as a whole. This article peers between the cracks in the extensive literature on Monteverdi’s compositional language and the Fifth Book to explore several idiosyncrasies of the collection, from the bass’s anomalous display in Cruda Amarilli and the book’s restriction to modes on G and D, to the puzzling change of system only four bars from the end of Ch’io t’ami, e t’ami più de la mia vita. Through this analysis, the Fifth Book becomes a snapshot of Monteverdi’s activities at the Mantuan court around 1600, not only as a composer, but also as an instrumentalist—as a performer on the viola bastarda.
Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans
Authors: Thijssen Dick H J , Bruno Rosa Maria , van Mil Anke C C M , Holder Sophie M , Faita Francesco , Greyling Arno , Zock Peter L , Taddei Stefano , Deanfield John E , Luscher Thomas , Green Daniel J , Ghiadoni Lorenzo
Published: May 2019

Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.
Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort
Authors: Rasmussen Katrine L , Tybjærg-Hansen Anne , Nordestgaard Børge G , Frikke-Schmidt Ruth
Published: May 2019

Aims

To determine whether plasma apoE levels and APOE genotype are associated with all-cause and cause-specific mortality.

Methods and results

Using a prospective cohort design with 105 949 white individuals from the general population, we tested the association between plasma apoE at study enrolment and death during follow-up, and whether this was independent of APOE genotype. We confirmed the well-known association between APOE genotypes and mortality. For all-cause, cardiovascular, and cancer mortality, high levels of apoE were associated with increased risk, while for dementia-associated mortality low levels were associated with increased risk. For the highest vs. the fifth septile of plasma apoE, hazard ratios (HRs) were 1.20 (95% confidence interval 1.12–1.28) for all-cause mortality, 1.28 (1.13–1.44) for cardiovascular mortality, and 1.18 (1.05–1.32) for cancer mortality. Conversely, for the lowest vs. the fifth septile the HR was 1.44 (1.01–2.05) for dementia-associated mortality. Results were similar in analyses restricted to APOE ɛ33 carriers. Examining genetically determined plasma apoE, a 1 mg/dL increase conferred risk ratios of 0.97 (0.92–1.03) for cardiovascular mortality and 1.01 (0.95–1.06) for cancer mortality, while a 1 mg/dL decrease conferred a risk ratio of 1.70 (1.36–2.12) for dementia-associated mortality.

Conclusion

High plasma levels of apoE were associated with increased all-cause, cardiovascular, and cancer mortality, however of a non-causal nature, while low levels were causally associated with increased dementia-associated mortality.
Listeriacontamination in chevon and mutton from retail meat shops and slaughter house environment of Punjab, India
Authors: Alka  , Singh Randhir , Kaur Simranpreet , Bedi Jasbir Singh
Published: May 2019

Listeria monocytogenes is recognized as an emerging pathogen, with limited information or statistics on this pathogen. Moreover, poor hygienic practices in the unorganized meat sector favor its growth and survival. Therefore, the present study was carried out in Punjab, India to assess the prevalence of Listeria spp. in chevon and mutton samples, followed by its characterization. The prevalence of Listeria in chevon, mutton and swab samples collected from butchers’ shops and slaughter houses was 1.82%, 3.21% and 6.66%, respectively. The 18 (2.67%) L. monocytogenes strains isolated from 786 samples carried one or more virulence-associated gene. Based on virulence genes, 6/18 isolates were potentially pathogenic. Serovar 4b (44.4%) was predominant, followed by serovars 1/2a (22.2%), 1/2b (22.2%) and 1/2c (11.1%). Detection of L. monocytogenes in meat and environment samples indicated poor hygiene, potential cross-contamination and risk of listeriosis to consumers and occupational workers. The findings of the study were also relevant to the fact that most of the slaughtering in Punjab, India is carried out in unorganized way, and this meat is not stored propery. Moreover, in the absence of a systematic foodborne disease surveillance and monitoring program, a database on foodborne diseases is absent, and needs to be established.
Physical Exercise Training Effect and Mediation Through Cardiorespiratory Fitness on Dual-Task Performances Differ in Younger–Old and Older–Old Adults
Authors: Bherer Louis , Langeard Antoine , Kaushal Navin , Vrinceanu Tudor , Desjardins-Crépeau Laurence , Langlois Francis , Kramer Arthur F
Published: May 2019

Objective

It has often been reported that dual-task (DT) performance declines with age. Physical exercise can help improve cognition, but these improvements could depend on cognitive functions and age groups. Moreover, the mechanisms supporting this enhancement are not fully elucidated. This study investigated the impacts of physical exercise on single- and dual-task performance in younger-old (<70) and older-old (70+) adults. The study also assessed whether the training effect on cognition was mediated by improvement in cardiorespiratory fitness.

Methods

One hundred forty-three participants (65–89 years) took part in a physical exercise intervention for 3 months or were assigned to a control group. All participants completed a DT paradigm and an estimated measure of cardiorespiratory fitness. Regression models were used to test the training effect on these outcomes, and mediation analyses were used to determine whether the training-related cognitive changes were mediated by changes in cardiorespiratory fitness.

Results

In 70+, training predicted improved processing speed (βc = −.33) and cardiorespiratory fitness (βa = .26) and the effect of training on processing speed was fully mediated by change in cardiorespiratory fitness (βab = −.12). In <70, training predicted improvement in task-set cost (βc = −.26) and change in cardiorespiratory fitness (βa = .30) but improvement in task-set cost was not entirely mediated by change in cardiorespiratory fitness.

Discussion

Results are discussed in terms of the mechanisms supporting DT performance improvement following physical exercise training in older adults.
Tiredness of Life in Older persons: A Qualitative Study on Nurses’ Experiences of Being Confronted With This Growing Phenomenon
Authors: Van Humbeeck Liesbeth , Dillen Let , Piers Ruth , Van Den Noortgate Nele
Published: May 2019

Background and Objectives

With worldwide aging it is imperative to understand nurses’ perceptions of tiredness of life (ToL) and their ways of dealing with an increasingly common phenomenon. Most research on ToL relates to older individuals’ experiences. This study aimed to gain insight into nurses’ (a) perceptions of, (b) attitude(s) toward, and (c) ways of dealing with ToL in older patients.

Research Design and Methods

Qualitative study with elements of constructivist grounded theory. Data were collected by means of semi-structured interviews between February 2016 and June 2017 with a purposive sample of 25 nurses working in home care and nursing homes.

Results

A careful consideration indicative of an oscillation between 3 levels (e.g., behavioral, cognitive, and affective) is present. The confrontation with persons having ToL instigates a cognitive process of searching to understand the state a person is in, which on its turn ensues in an emotional balancing between courage and powerlessness and a behavioral approach of action or dialogue.

Discussion and Implications

Our findings indicate that nurses aim to provide good care, sensitive to the older person’s needs, but this process is not without ambiguity. This study provides nurse managers with valuable guidance to (a) support nursing staff in dealing with ToL, and (b) advance opportunities for emotionally sensitive care and (individual- and team-based) reflection. Finally, this study offers suggestions for education programs to incorporate ToL in curricula.
Seismic scatterers in the lower mantle near subduction zones
Authors: Kaneshima Satoshi
Published: May 2019

We investigate the global distribution of S-to-P scatterers in the shallow to mid-lower mantle beneath subduction zones, where deep seismicity extends down to the bottom of the upper mantle. By array processing broadband and short period waveform data obtained at seismic networks, we seek anomalous later phases in the P coda within about 15–150 s after direct P waves. The later phases usually arrive along off-great circle paths and significantly later than S-to-P conversion from the ‘660 km’ discontinuity, often show positive slowness anomalies relative to direct P, and do not show a conversion depth that is consistent among nearby events. They are thus adequately regarded as scattered waves, rather than conversion at a global horizontal discontinuity. The S-to-P scattered waves often show amplitudes comparable to ‘S660P’ waves, which indicates that a spatial change in elastic properties by several percent occurs at the scatterers as abruptly as the post-spinel transformation and should arise from compositional heterogeneity. We locate prominent S-to-P scatterers beneath Pacific subduction zones and beneath southern Spain. Nearly half of 137 S-to-P scatterers located in this study and previous studies by the authors are shallower than 1000 km, and the number of scatterers decreases with depth. Scatterers deeper than 1800 km are rare and mostly weak. We examine relations between the locations of the scatterers and recently subducted slabs inferred from seismic tomography. The scatterers of mid-mantle depths, deeper than about 1000 km, are located distant from tomographic slabs. On the other hand, the majority of shallower scatterers are located beneath the slabs rather than near their fastest portions, which would indicate that chemically heterogeneous materials are not extensively entrained within thickened and folded slabs when the slabs impinge on the lower mantle. We also find scatterers near the locations where basaltic rocks of recently subducted oceanic crust are expected to exist, which suggests that oceanic crust is not delaminating when slabs impinge on the lower mantle.
How to foster informed decision making about food supplements: results from an international Delphi study
Authors: de Vries Hein , Pajor Emï¿½lia M , Curfs Kenny C J , Eggers Sander M , Oenema Anke
Published: May 2019

Food supplement use can have beneficial and detrimental effects, making informed decisions about supplement use important. How these decisions are made and which communication strategies can stimulate informed decision making is unclear. This study identified the important characteristics of (i) informed decision making about food supplement use and (ii) important factors indicating how to communicate about food supplements to foster informed decision making. An online three-round Delphi study was conducted. International experts within the field of (risk) communication about food supplements or related fields were recruited via email. The participants' age ranged from 25 to 69 years, and sample sizes for the three rounds were 38, 89 and 51, respectively. Experts indicated that for making an informed decision about food supplement use one needs to have knowledge of their positive and negative effects, the ability to compare these effects, knowing alternatives besides supplements, feeling informed, and feeling able (self-efficacious) to make the decision and making the decision voluntarily. Important communication strategies mentioned were: provision of information about positive and negative effects and the nature of these effects including scientific evidence, ensuring information is easily accessible, well ordered, tailored and provided by a trustworthy, credible and independent source.
Regional entrepreneurial ecosystems in China
Authors: Lai Yanzhao , Vonortas Nicholas S
Published: May 2019

This study focuses on regional entrepreneurial ecosystems in the largest emerging economy in the world. We use a two-stage structural model distinguishing between two sets of factors, those that have direct impact on entrepreneurial activities and those that have indirect impact. Based on an empirical analysis of 263 Chinese prefecture-level municipalities from 2008 to 2015, we find that human capital, knowledge creation, and access to finance are the main factors that drive local entrepreneurial activity. New technology-based startups are significant predictors of the regional stock of human capital and the presence of risk finance suggesting the unique role of technology-based firms in promoting sustainable growth in regional entrepreneurial ecosystems. The presence of research-intensive universities also has a strong positive impact on regional entrepreneurial ecosystems.
Bott–Samelson Varieties and Poisson Ore Extensions
Authors: Elek Balázs , Lu Jiang-Hua
Published: May 2019

We show that associated with any $n$-dimensional Bott–Samelson variety of a complex semi-simple Lie group $G$, one has $2^n$ Poisson brackets on the polynomial algebra $A={\mathbb{C}}[z_1, \ldots , z_n]$, each an iterated Poisson Ore extension and one of them a symmetric Poisson Cauchon–Goodearl–Letzter (CGL) extension in the sense of Goodearl–Yakimov. We express the Poisson brackets in terms of root strings and structure constants of the Lie algebra of $G$. It follows that the coordinate rings of all generalized Bruhat cells have presentations as symmetric Poisson CGL extensions. The paper establishes the foundation on generalized Bruhat cells and sets the stage for their applications to integrable systems, cluster algebras, total positivity, and toric degenerations of Poisson varieties, some of which are discussed in the Introduction.
The Role of Iron in the Susceptibility of Neonatal Mice to Escherichia coli K1 Sepsis
Authors: Michels Kathryn R , Lambrecht Nathalie J , Carson William F , Schaller Matthew A , Lukacs Nicholas W , Bermick Jennifer R
Published: May 2019

Sepsis from Escherichia coli expressing the K1 antigen is a leading cause of death in neonates. In a murine model, E. coli K1 grew rapidly in the peritoneal cavity of neonatal mice, causing fatal disease. In contrast, adult mice cleared the infection. Neonatal mice mounted a rapid and equivalent antimicrobial immune response compared to adult mice. Interestingly, peritoneal fluid from neonatal mice contained significantly more total iron than that of adult mice, which was sufficient to support enhanced E. coli growth. Transient iron overload in adult mice infected with E. coli resulted in 100% mortality. Maternal diet–induced mild iron deficiency decreased offspring peritoneal iron, decreased bacterial growth, and conferred protection against sepsis. Taken together, neonatal susceptibility to E. coli K1 sepsis is enhanced by a localized excess of peritoneal iron that allows for unchecked bacterial growth. Targeting this excess iron may provide a new therapeutic target in human patients.
Theoretical modeling reveals that regulatory T cells increase T-cell interaction with antigen-presenting cells for stable immune tolerance
Authors: Yamaguchi Tomoyuki , Teraguchi Shunsuke , Furusawa Chikara , Machiyama Hiroaki , Watanabe Tomonobu M , Fujita Hideaki , Sakaguchi Shimon , Yanagida Toshio
Published: May 2019

The immune system in tolerance maintains cell diversity without responding to self-antigens. Foxp3-expressing CD25+CD4+ regulatory T cells (Tregs) inhibit T-cell activation through various molecular mechanisms. However, several key questions are still not resolved, including how Tregs control the immune response on the basis of their self-skewed T-cell receptor repertoire and how Tregs avoid impeding relevant immunity against pathogens. Here, we show that Tregs promote the proliferation of conventional T cells in the presence of excessive co-stimulation when murine T cells are stimulated in vitro with allogeneic antigen-presenting cells (APCs). Antigen-specific Tregs increase the number of cells interacting with dendritic cells (DCs) by increasing the number of viable DCs and the expression of adhesion molecules on DCs. Theoretical simulations and mathematical models representing the dynamics of T-APC interaction and T-cell numbers in a lymph node indicate that Tregs reduce the dissociation probability of T cells from APCs and increase the new association. These functions contribute to tolerance by enhancing the interaction of low-affinity T cells with APCs. Supporting the theoretical analyses, we found that reducing the T-cell numbers in mice increases the ratio of specific T cells among CD4+ T cells after immunization and effectively induces autoimmune diabetes in non obese diabetes mice. Thus, as a critical function, antigen-specific Tregs stabilize the immune state, irrespective of it being tolerant or responsive, by augmenting T-APC interaction. We propose a novel regulation model in which stable tolerance with large heterogeneous populations proceeds to a specific immune response through a transient state with few populations.
Adverse drug events and medication relation extraction in electronic health records with ensemble deep learning methods
Authors: Christopoulou Fenia , Tran Thy Thy , Sahu Sunil Kumar , Miwa Makoto , Ananiadou Sophia
Published: May 2019

Objective

Identification of drugs, associated medication entities, and interactions among them are crucial to prevent unwanted effects of drug therapy, known as adverse drug events. This article describes our participation to the n2c2 shared-task in extracting relations between medication-related entities in electronic health records.

Materials and Methods

We proposed an ensemble approach for relation extraction and classification between drugs and medication-related entities. We incorporated state-of-the-art named-entity recognition (NER) models based on bidirectional long short-term memory (BiLSTM) networks and conditional random fields (CRF) for end-to-end extraction. We additionally developed separate models for intra- and inter-sentence relation extraction and combined them using an ensemble method. The intra-sentence models rely on bidirectional long short-term memory networks and attention mechanisms and are able to capture dependencies between multiple related pairs in the same sentence. For the inter-sentence relations, we adopted a neural architecture that utilizes the Transformer network to improve performance in longer sequences.

Results

Our team ranked third with a micro-averaged F1 score of 94.72% and 87.65% for relation and end-to-end relation extraction, respectively (Tracks 2 and 3). Our ensemble effectively takes advantages from our proposed models. Analysis of the reported results indicated that our proposed approach is more generalizable than the top-performing system, which employs additional training data- and corpus-driven processing techniques.

Conclusions

We proposed a relation extraction system to identify relations between drugs and medication-related entities. The proposed approach is independent of external syntactic tools. Analysis showed that by using latent Drug-Drug interactions we were able to significantly improve the performance of non–Drug-Drug pairs in EHRs.
Effect of sodium ions on conformations of the cytoplasmic loop of the PomA stator protein of Vibrio alginolyticus
Authors: Mino Taira , Nishikino Tatsuro , Iwatsuki Hiroto , Kojima Seiji , Homma Michio
Published: May 2019

The sodium driven flagellar stator of Vibrio alginolyticus is a hetero-hexamer membrane complex composed of PomA and PomB, and acts as a sodium ion channel. The conformational change in the cytoplasmic region of PomA for the flagellar torque generation, which interacts directly with a rotor protein, FliG, remains a mystery. In this study, we introduced cysteine mutations into cytoplasmic charged residues of PomA, which are highly conserved and interact with FliG, to detect the conformational change by the reactivity of biotin maleimide. In vivo labelling experiments of the PomA mutants revealed that the accessibility of biotin maleimide at position of E96 was reduced with sodium ions. Such a reduction was also seen in the D24N and the plug deletion mutants of PomB, and the phenomenon was independent in the presence of FliG. This sodium ions specific reduction was also detected in Escherichia coli that produced PomA and PomB from a plasmid, but not in the purified stator complex. These results demonstrated that sodium ions cause a conformational change around the E96 residue of loop2–3 in the biological membrane.
Characterization and Expression of Genes Encoding Superoxide Dismutase in the Oriental Armyworm, Mythimna separata (Lepidoptera: Noctuidae)
Authors: Li Hong-Bo , Dai Chang-Geng , He Yong-Fu , Hu Yang
Published: May 2019

Superoxide dismutase (SOD) is an antioxidant metalloenzyme that catalyzes the dismutation of the superoxide anion O2− to O2 and H2O2. Many studies have focused on the role of SOD in response to abiotic stress, but its role during biotic stress, such as changes in organismal population density, has rarely been investigated. The oriental armyworm, Mythimna separata, is an economically important pest that exhibits phenotypic changes in response to population density. Solitary and gregarious phases occur at low and high population density, respectively. To examine the role of SODs in response to population density stress, we cloned two genes encoding SOD, MsCuZnSOD and MsMnSOD, and compared their expression in solitary and gregarious phases of M. separata. The MsCuZnSOD and MsMnSOD ORFs were 480 and 651 bp and encoded predicted protein products of 159 and 216 amino acids, respectively. The two SODs contained motifs that are typical of orthologous proteins. Real-time PCR indicated that the two SOD genes were expressed throughout developmental stages and were significantly upregulated in more mature stages of gregarious M. separata. Expression of the two SOD genes in various tissues of sixth-instar larvae was higher in gregarious versus solitary insects. Furthermore, expression of the SOD genes was significantly upregulated in response to crowding in solitary individuals, but suppressed in gregarious insects subjected to isolation. Collectively, these results suggest that population density may be key factor in the induction of SOD genes in M. separata.
Traditional Cardiovascular Risk Factors and Individual Prediction of Cardiovascular Events in Childhood Cancer Survivors
Authors: Chen Yan , Chow Eric J , Oeffinger Kevin C , Border William L , Leisenring Wendy M , Meacham Lillian R , Mulrooney Daniel A , Sklar Charles A , Stovall Marilyn , Robison Leslie L , Armstrong Gregory T , Yasui Yutaka
Published: May 2019

Background

Childhood cancer survivors have an increased risk of heart failure, ischemic heart disease, and stroke. They may benefit from prediction models that account for cardiotoxic cancer treatment exposures combined with information on traditional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes.

Methods

Childhood Cancer Survivor Study participants (n = 22 643) were followed through age 50 years for incident heart failure, ischemic heart disease, and stroke. Siblings (n = 5056) served as a comparator. Participants were assessed longitudinally for hypertension, dyslipidemia, and diabetes based on self-reported prescription medication use. Half the cohort was used for discovery; the remainder for replication. Models for each outcome were created for survivors ages 20, 25, 30, and 35 years at the time of prediction (n = 12 models).

Results

For discovery, risk scores based on demographic, cancer treatment, hypertension, dyslipidemia, and diabetes information achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater in 9 and 10 of the 12 models, respectively. For replication, achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater were observed in 7 and 9 of the models, respectively. Across outcomes, the most influential exposures were anthracycline chemotherapy, radiotherapy, diabetes, and hypertension. Survivors were then assigned to statistically distinct risk groups corresponding to cumulative incidences at age 50 years of each target outcome of less than 3% (moderate-risk) or approximately 10% or greater (high-risk). Cumulative incidence of all outcomes was 1% or less among siblings.

Conclusions

Traditional cardiovascular risk factors remain important for predicting risk of cardiovascular disease among adult-age survivors of childhood cancer. These prediction models provide a framework on which to base future surveillance strategies and interventions.
A multi-institutional and case-matched control study on treatment outcomes of consolidative radiotherapy after a full course of R-CHOP compared with R-CHOP alone in Stage I–II diffuse large B-cell lymphoma (KROG 17-02)
Authors: Chung Mi Joo , Cho Won Kyung , Oh Dongryul , Eom Keun-Yong , Kim Jin Hee , Kim Woo Chul , Lee Jong Hoon
Published: May 2019

We compared treatment outcomes between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy alone with R-CHOP followed by consolidative radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL). We analyzed 404 patients with Stage I–II DLBCL who received six to eight cycles of R-CHOP and achieved a good response after a full course of chemotherapy. Propensity-score matching was used to assess the role of consolidative RT. The R-CHOP alone group (n = 184) was matched in a 1:2 ratio with the R-CHOP plus RT group (n = 92). Twenty-four (13.0%) of 184 patients receiving R-CHOP alone and 8 (8.7%) of 92 patients receiving R-CHOP plus RT had bulky diseases (>7.5 cm). A Deauville score of 1–2 was achieved for 159 (86.4%) of 184 patients receiving R-CHOP alone and 84 (91.3%) of 92 patients receiving R-CHOP plus RT. After a median follow-up time of 42 months, the recurrence-free survival (RFS) rate (86.7% vs 93.0%, P = 0.464) and overall survival rate (88.3% vs 95.1%, P = 0.295) at 5 years did not differ significantly between the R-CHOP alone and R-CHOP plus RT arms. In the additional multivariate analyses, large tumor size (>7.5 cm) was significantly associated with decreased RFS (hazard ratio, 2.368 and confidence interval, 1.837–6.697; P = 0.048). Consolidative radiation was not a significant factor for RFS (P = 0.563). Tumor size was a significant factor for RFS in the rituximab era. The outcome of omitting consolidative RT for good responders after six to eight cycles of R-CHOP chemotherapy was acceptable in early-stage DLBCL without a bulky disease.
Regional and Rural–Urban Variation in Opioid Prescribing in the Veterans Health Administration
Authors: Lund Brian C , Ohl Michael E , Hadlandsmyth Katherine , Mosher Hilary J
Published: May 2019

Introduction

Opioid prescribing is heterogenous across the US, where 3- to 5-fold variation has been observed across states or other geographical units. Residents of rural areas appear to be at greater risk for opioid misuse, mortality, and high-risk prescribing. The Veterans Health Administration (VHA) provides a unique setting for examining regional and rural–urban differences in opioid prescribing, as a complement and contrast to extant literature. The objective of this study was to characterize regional variation in opioid prescribing across Veterans Health Administration (VHA) and examine differences between rural and urban veterans.

Materials and Methods

Following IRB approval, this retrospective observational study used national administrative VHA data from 2016 to assess regional variation and rural–urban differences in schedule II opioid prescribing. The primary measure of opioid prescribing volume was morphine milligram equivalents (MME) dispensed per capita. Secondary measures included incidence, prevalence of any use, and prevalence of long-term use.

Results

Among 4,928,195 patients, national VHA per capita opioid utilization in 2016 was 1,038 MME. Utilization was lowest in the Northeast (894 MME), highest in the West (1,368 MME), and higher among rural (1,306 MME) than urban (988 MME) residents (p < 0.001). Most of the difference between rural and urban veterans (318 MME) was attributable to differences in long-term opioid use (312 MME), with similar rates of short-term use.

Conclusion

There is substantial regional and rural–urban variation in opioid prescribing in VHA. Rural veterans receive over 30% more opioids than their urban counterparts. Further research is needed to identify and address underlying causes of these differences, which could include access barriers for non-pharmacologic treatments for chronic pain.
Functional Movement Assessments Are Not Associated with Risk of Injury During Military Basic Training
Authors: de la Motte Sarah J , Clifton Daniel R , Gribbin Timothy C , Beutler Anthony I , Deuster Patricia A
Published: May 2019

Introduction

Musculoskeletal injuries (MSK-I) in the U.S. military accounted for more than four million medical encounters in 2017. The Military Entrance Processing Screen to Assess Risk of Training (MEPSTART) was created to identify MSK-I risk during the first 180 days of military service.

Methods

Active duty applicants to the United States Army, Navy, Air Force, and Marine Corps between February 2013 and December 2014 who consented completed a behavioral and injury history questionnaire and the MEPSTART screen [Functional Movement Screen (FMS), Y-Balance Test (YBT), Landing Error Scoring System (LESS), and Overhead Squat assessment (OHS)] the day they shipped to basic training. Male (n = 1,433) and Female (n = 281) applicants were enrolled and MSK-I were tracked for 180 days. Binomial logistic regression and multivariate Cox proportional hazards modeling were used to assess relationships among MEPSTART screens and MSK-I independent of age, BMI, sex, Service, injury history, and smoking status. Analyses were finalized and performed in 2017.

Results

The only functional screen related to injury was the LESS score. Compared to those with good LESS scores, applicants with poor LESS scores had lower odds of MSK-I (OR = 0.54, 95% CI = 0.30–0.97, p = 0.04), and a lower instantaneous risk of MSK-I during the first 180 d (HR = 0.58, 95%CI = 0.34–0.96, p = 0.04). However, secondary receiver operator characteristic (ROC) analyses revealed poor discriminative value (AUC = 0.49, 95%CI = 0.43–0.54).

Conclusions

Functional performance did not predict future injury risk during the first 180 days of service. Poor LESS scores were associated with lower injury risk, but ROC analyses revealed little predictive value and limited clinical usefulness. Comprehensive risk reduction strategies may be preferable for mitigating MSK-I in military training populations.
ASASSN-18tb: a most unusual Type Ia supernova observed by TESS and SALT
Authors: Vallely P J , Fausnaugh M , Jha S W , Tucker M A , Eweis Y , Shappee B J , Kochanek C S , Stanek K Z , Chen Ping , Dong Subo , Prieto J L , Sukhbold T , Thompson Todd A , Brimacombe J , Stritzinger M D , Holoien T W-S , Buckley D A H , Gromadzki M , Bose Subhash
Published: May 2019

We present photometric and spectroscopic observations of the unusual Type Ia supernova ASASSN-18tb, including a series of Southern African Large Telescope spectra obtained over the course of nearly six months and the first observations of a supernova by the Transiting Exoplanet Survey Satellite. We confirm a previous observation by Kollmeier et al. showing that ASASSN-18tb is the first relatively normal Type Ia supernova to exhibit clear broad (∼1000 km s−1) H α emission in its nebular-phase spectra. We find that this event is best explained as a sub-Chandrasekhar mass explosion producing $M_{\mathrm{ Ni}} \approx 0.3\,\, \rm {M}_\odot$. Despite the strong H α signature at late times, we find that the early rise of the supernova shows no evidence for deviations from a single-component power-law and is best fit with a moderately shallow power law of index 1.69 ± 0.04. We find that the H α luminosity remains approximately constant after its initial detection at phase +37 d, and that the H α velocity evolution does not trace that of the Fe iii λ4660 emission. These suggest that the H α emission arises from a circumstellar medium (CSM) rather than swept-up material from a non-degenerate companion. However, ASASSN-18tb is strikingly different from other known CSM-interacting Type Ia supernovae in a number of significant ways. Those objects typically show an H α luminosity two orders of magnitude higher than what is seen in ASASSN-18tb, pushing them away from the empirical light-curve relations that define ‘normal’ Type Ia supernovae. Conversely, ASASSN-18tb exhibits a fairly typical light curve and luminosity for an underluminous or transitional SN Ia, with MR ≈ −18.1 mag. Moreover, ASASSN-18tb is the only SN Ia showing H α from CSM interaction to be discovered in an early-type galaxy.
Faraday rotation measure dependence on galaxy cluster dynamics
Authors: Stasyszyn F A , de los Rios M
Published: May 2019

We study the magnetic fields in galaxy clusters through Faraday rotation measurements crossing systems in different dynamical states. We confirm that magnetic fields are present in those systems and analyse the difference between relaxed and unrelaxed samples with respect to the dispersion between their inherent Faraday rotation measurements (RM). We found an increase of this RM dispersion and a higher RM overlapping frequency for unrelaxed clusters. This fact suggests that a large-scale physical process is involved in the nature of unrelaxed systems and possible depolarization effects are present in the relaxed ones. We show that dynamically unrelaxed systems can enhance magnetic fields to large coherence lengths. In contrast, the results for relaxed systems suggests that a small-scale dynamo can be a dominant mechanism for sustaining magnetic fields, leading to intrinsic depolarization.
Gaia stellar kinematics in the head of the Orion A cloud: runaway stellar groups and gravitational infall
Authors: Getman K V , Feigelson E D , Kuhn M A , Garmire G P
Published: May 2019

This work extends previous kinematic studies of young stars in the head of the Orion A cloud (OMC-1/2/3/4/5). It is based on large samples of infrared, optical, and X-ray selected pre-main-sequence stars with reliable radial velocities and Gaia-derived parallaxes and proper motions. Stellar kinematic groups are identified assuming they mimic the motion of their parental gas. Several groups are found to have peculiar kinematics: the NGC 1977 cluster and two stellar groups in the extended Orion nebula (EON) cavity are caught in the act of departing their birthplaces. The abnormal motion of NGC 1977 may have been caused by a global hierarchical cloud collapse, feedback by massive Ori OB1ab stars, supersonic turbulence, cloud–cloud collision, and/or slingshot effect; the former two models are favoured by us. EON groups might have inherited anomalous motions of their parental cloudlets due to small-scale ‘rocket effects’ from nearby OB stars. We also identify sparse stellar groups to the east and west of Orion A that are drifting from the central region, possibly a slowly expanding halo of the Orion nebula cluster. We confirm previously reported findings of varying line-of-sight distances to different parts of the cloud’s Head with associated differences in gas velocity. 3D movies of star kinematics show contraction of the groups of stars in OMC-1 and global contraction of OMC-123 stars. Overall, the head of Orion A region exhibits complex motions consistent with theoretical models involving hierarchical gravitational collapse in (possibly turbulent) clouds with OB stellar feedback.
Solvent viscosity facilitates replication and ribozyme catalysis from an RNA duplex in a model prebiotic process
Authors: He Christine , Lozoya-Colinas Adriana , Gállego Isaac , Grover Martha A , Hud Nicholas V
Published: May 2019

The RNA World hypothesis posits that RNA was once responsible for genetic information storage and catalysis. However, a prebiotic mechanism has yet to be reported for the replication of duplex RNA that could have operated before the emergence of polymerase ribozymes. Previously, we showed that a viscous solvent enables information transfer from one strand of long RNA duplex templates, overcoming ‘the strand inhibition problem'. Here, we demonstrate that the same approach allows simultaneous information transfer from both strands of long duplex templates. An additional challenge for the RNA World is that structured RNAs (like those with catalytic activity) function poorly as templates in model prebiotic RNA synthesis reactions, raising the question of how a single sequence could serve as both a catalyst and as a replication template. Here, we show that a viscous solvent also facilitates the transition of a newly synthesized hammerhead ribozyme sequence from its inactive, duplex state to its active, folded state. These results demonstrate how fluctuating environmental conditions can allow a ribozyme sequence to alternate between acting as a template for replication and functioning as a catalyst, and illustrate the potential for temporally changing environments to enable molecular processes necessary for the origin of life.
Assumption of Risk and the Role of Health Warnings Labels in the United States
Authors: Cummings K Michael , Gdanski Jonathan , Veatch Nichole , Sebrié Ernesto Marcelo
Published: May 2019

Introduction

This article provides historical context for understanding how the cigarette industry have manipulated language used in health warning labels (HWLs) to protect them in litigation.

Methods

Review of previously secret internal business records from 1964 discussing the role HWLs on cigarettes. Review of the legal challenges made by cigarette manufacturers surrounding HWLs as mandated in the 2009 Family Smoking Prevention and Tobacco Control Act and the language in corrective statements ordered by US Department of Justice.

Results

Within days after the Surgeon General’s Advisory Committee issued its 1964 Report the cigarette companies plotted how they could use HWLs on cigarettes as a defense in future litigation. Industry lawyers discussed drafting legislation that would preempt other government agencies from requiring HWLs on cigarette containers and in cigarette advertising with language mirroring the key findings of the Surgeon General’s Advisory Committee report. In July 1965, Congress did pass legislation which mandated a single watered-down cigarette pack HWL which excluded cigarette advertising, just as industry lawyers had recommended. Subsequent HWL laws passed by Congress in 1969 and 1984 along with the more recent history of manufacturers opposing updated graphic HWLs and corrective statements reflects a consistent and continuing effort by cigarette companies to insulate themselves from taking responsibility for harms caused by smoking.

Conclusion

Beginning in the mid-1960s and continuing even through today, lawyers working on behalf of cigarettes companies have worked to manipulate the language of consumer warnings to focus responsibility for the harms caused by smoking on smokers.

Implications

In tobacco litigation, juries should be informed about the industry’s coordinated effort to draft legislation and water down the original caution statements proposed on cigarette containers and in advertising even though Congress ultimately is responsible for the law that was enacted. In addition, even though the 1992 Supreme Court decision in the Cipollone case preempted post-1969 failure to warm claims against cigarette makers, this protection does not apply on pre-1969 warning claims where the evidence shows that cigarette companies understood they were selling a defective product that when used as intended would harm their customers. Thus, those initiating smoking before 1969 and subsequently harmed by cigarettes can hold cigarette makers responsible for their failure to warn them about health risks.
Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials
Authors: Cui Chendi , Birru Rahel L , Snitz Beth E , Ihara Masafumi , Kakuta Chikage , Lopresti Brian J , Aizenstein Howard J , Lopez Oscar L , Mathis Chester A , Miyamoto Yoshihiro , Kuller Lewis H , Sekikawa Akira
Published: May 2019

Context

The results of preclinical and observational studies support the beneficial effect of soy isoflavones on cognition.

Objective

This review aimed to evaluate the effects of soy isoflavones on cognition in adults.

Data Sources

The PUBMED, EMBASE, Ovid Medline, Cochrane Library, and clinicaltrials.gov databases were searched.

Study Selection

Two researchers independently screened 1955 records, using the PICOS criteria: participants were adults; intervention was dietary sources with soy isoflavones or isolated soy isoflavones; comparator was any comparator; outcome was cognitive function; study type was randomized controlled trials (RCTs). A third researcher was consulted to resolve any discrepancies. Sixteen RCTs were included and their quality assessed.

Data Extraction

Information on study design, characteristics of participants, and outcomes was extracted. PRISMA guidelines were followed.

Data Analysis

A random-effects meta-analysis was used to pool estimates across studies. In the 16 RCTs (1386 participants, mean age = 60 y), soy isoflavones were found to improve overall cognitive function (standardized mean difference [SMD], 0.19; 95% confidence interval [CI], 0.07–0.32) and memory (SMD, 0.15; 95%CI, 0.03–0.26).

Conclusion

The results showed that soy isoflavones may improve cognitive function in adults.

Systematic Review Registration

PROSPERO registration no. CRD42018082070.