bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014‐2018)
Authors: Tomlinson Joy E. , Kapoor Amit , Kumar Arvind , Tennant Bud C. , Laverack Melissa A. , Beard Laurie , Delph Katie , Davis Elizabeth , Schott II Harold , Lascola Kara , Holbrook Todd C. , Johnson Philip , Taylor Sandra D. , McKenzie Erica , Carter‐Arnold Jessica , Setlakwe Emilie , Fultz Lisa , Brakenhoff Jeff , Ruby Rebecca , Trivedi Sheetal , Van de Walle Gerlinde R. , Renshaw Randall W. , Dubovi Edward J. , Divers Thomas J.
Published: December 2018

Background

Three flaviviruses (equine pegivirus [EPgV]; Theiler's disease–associated virus [TDAV]; non‐primate hepacivirus [NPHV]) and equine parvovirus (EqPV‐H) are present in equine blood products; the TDAV, NPHV, and EqPV‐H have been suggested as potential causes of serum hepatitis.

Objective

To determine the prevalence of these viruses in horses with equine serum hepatitis.

Animals

Eighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals.

Methods

In the prospective case study, liver, serum, or both samples were tested for EPgV, TDAV, NPHV, and EqPV‐H by PCR.

Results

Both liver tissue and serum were tested for 6 cases, serum only for 8 cases, and liver only for 4 cases. Twelve horses received tetanus antitoxin (TAT) 4‐12.7 weeks (median = 8 weeks), 3 horses received commercial equine plasma 6‐8.6 weeks, and 3 horses received allogenic stem cells 6.4‐7.6 weeks before the onset of hepatic failure. All samples were TDAV negative. Two of 14 serum samples were NPHV‐positive. Six of 14 serum samples were EPgV‐positive. All liver samples were NPHV‐negative and EPgV‐negative. EqPV‐H was detected in the serum (N = 8), liver (N = 4), or both samples (N = 6) of all 18 cases. The TAT of the same lot number was available for virologic testing in 10 of 12 TAT‐associated cases, and all 10 samples were EqPV‐H positive.

Conclusions and Clinical Importance

We demonstrated EqPV‐H in 18 consecutive cases of serum hepatitis. EPgV, TDAV, and NPHV were not consistently present. This information should encourage blood product manufacturers to test for EqPV‐H and eliminate EqPV‐H–infected horses from their donor herds.
Genome‐wide patterns of transposon proliferation in an evolutionary young hybrid fish
Authors: Dennenmoser Stefan , Sedlazeck Fritz J. , Schatz Michael C. , Altmüller Janine , Zytnicki Matthias , Nolte Arne W.
Published: December 2018

Hybridization can induce transposons to jump into new genomic positions, which may result in their accumulation across the genome. Alternatively, transposon copy numbers may increase through nonallelic (ectopic) homologous recombination in highly repetitive regions of the genome. The relative contribution of transposition bursts versus recombination‐based mechanisms to evolutionary processes remains unclear because studies on transposon dynamics in natural systems are rare. We assessed the genomewide distribution of transposon insertions in a young hybrid lineage (“invasive Cottus”, n = 11) and its parental species Cottus rhenanus (n = 17) and Cottus perifretum(n = 9) using a reference genome assembled from long single molecule pacbio reads. An inventory of transposable elements was reconstructed from the same data and annotated. Transposon copy numbers in the hybrid lineage increased in 120 (15.9%) out of 757 transposons studied here. The copy number increased on average by 69% (range: 10%–197%). Given the age of the hybrid lineage, this suggests that they have proliferated within a few hundred generations since admixture began. However, frequency spectra of transposon insertions revealed no increase in novel and rare insertions across assembled parts of the genome. This implies that transposons were added to repetitive regions of the genome that remain difficult to assemble. Future studies will need to evaluate whether recombination‐based mechanisms rather than genomewide transposition may explain the majority of the recent transposon proliferation in the hybrid lineage. Irrespectively of the underlying mechanism, the observed overabundance in repetitive parts of the genome suggests that gene‐rich regions are unlikely to be directly affected.
I. INTRODUCTION: THE CO‐CONSTRUCTION OF MOTHER–CHILD ATTACHMENT RELATIONSHIPS IN EARLY CHILDHOOD
Authors: Posada Germán E. , Waters Harriet S.
Published: December 2018

Attachment relationships are formed, organized, and elaborated through interactions between an attachment figure and her/his child. The parent–child codetermination process that establishes their relationship in infancy extends and expands during the preschool years. A child's developing ability to use her/his mother as a secure base requires support, time, and practice during early childhood. Moreover, experiences with attachment figures provide information that children use to build internal representations of their relationship. Thus, the organization of attachment behavior is expected to be related to the structure of a child's attachment representations. Yet, questions about how the structure of those representations develop remain unanswered. In moving into the preschool years, we anticipate that building of mental representations of secure base support and use will be guided by parent–child co‐construction processes. The child's improving language and advancing information processing skills increase the opportunities for verbally based interactions between caregiver and child. The mother–child co‐construction process of secure base relationships includes now a verbal‐representational component, but the nonverbal, behavioral building blocks remain in play as well.
V. MATERNAL SENSITIVITY AND CO‐CONSTRUCTION SKILLS: CONCURRENT AND LONGITUDINAL ASSOCIATIONS WITH PRESCHOOLERS’ SECURE BASE BEHAVIOR
Authors: Lu Ting , Posada Germán E. , Trumbell Jill M. , Anaya Laura
Published: December 2018

This study investigated the associations among maternal sensitivity, maternal secure base script co‐construction skills, and children's secure base behavior during early childhood. Maternal sensitivity and children's secure base behavior were assessed in naturalistic settings among 81 mother–child dyads when the children were approximately 3.5 years old. Maternal co‐construction skills were also assessed at that age via a joint mother–child storytelling task. Maternal sensitivity and secure base behavior were assessed again when children (N = 74) were about 5.5 years old. Results indicated that mother sensitivity assessed at the early age was significantly related to maternal co‐construction skills. Maternal co‐constructive skills in turn were also significantly associated with children's secure base behavior both concurrently and longitudinally. Finally, regression analyses indicated both maternal sensitivity, concurrently at each point in time, and co‐construction skills contributed unique and significant information to the prediction of child secure base behavior.
VI. INTERGENERATIONAL TRANSMISSION OF SECURE BASE SCRIPT KNOWLEDGE: THE ROLE OF MATERNAL CO‐CONSTRUCTION SKILLS
Authors: Apetroaia Adela , Waters Harriet S.
Published: December 2018

This study examined the link between mothers’ and children's script‐like representations of attachment and the role of maternal co‐construction skills in facilitating script knowledge in their children. Fifty‐nine children recruited from preschools in Bucharest, Romania (age range 4 to 5 years) completed a shortened version of the Attachment Story Completion Task (ASCT) to assess their secure base script knowledge whereas their mother's script knowledge was assessed with the Attachment Script Assessment (ASA). In addition, the mother–child pairs completed the Affect Discussion Task (see Chapter II) to assess mothers’ co‐construction skills. Mother and child secure base script knowledge was significantly related, as were maternal co‐construction skills and child script knowledge. Regression analyses indicated that maternal co‐construction skills impacted children's script knowledge above and beyond the effects of maternal script scores.
The usefulness of [123I]‐metaiodobenzylguanidine myocardial scintigraphy in patients with subacute myelo‐optico‐neuropathy
Authors: Konishi Tetsuro , Fujiki Naoto
Published: December 2018

Background

Patients with subacute myelo‐optico‐neuropathy (SMON), caused by clioquinol intoxication more than 40 years ago, had been suffered from various kinds of autonomic disorders, such as diarrhea, constipation, and incontinence. [123I]‐metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a sensitive test for diagnosis of Parkinson's disease (PD).

Aim

We tried to clarify the usefulness of MIBG myocardial scintigraphy in SMON patients for diagnosing PD.

Methods

The MIBG myocardial scintigraphy was investigated in fifteen SMON patients who were suffered from various kinds of autonomic symptoms. In these SMON patients, four patients (mean age ± SD; 73.3 ± 6.8) showed early stage of PD, whose Hoehn–Yahr (H–Y) stage was stage I or stage II, but the other eleven patients (mean age ± SD; 78.0 ± 7.6) had not any signs or symptoms of Parkinsonism.

Results

Four patients with early stages of PD showed significantly reduced MIBG uptake. Eleven patients except one without Parkinsonism showed normal MIBG uptake. No apparent relation between the degree of the autonomic symptoms and the MIBG uptake was observed. One patient without Parkinsonism showed significantly reduced MIBG uptake and was suggested to be suffered from a preclinical state of PD, since the [123I]‐ioflupane single‐photon emission computed tomography scintigraphy showed decreased uptake of isotopes in the bilateral striate regions 8 years after the MIBG myocardial scintigraphy.

Conclusion

The MIBG myocardial scintigraphy in SMON patients with various kinds of autonomic symptoms is useful as a highly sensitive and specific tool for diagnosing PD.
Methane production and emissions in trees and forests
Authors: Covey Kristofer R. , Megonigal J. Patrick
Published: December 2018

Contents

Summary
35

I.
Introduction
36

II.
Tree CH4 fluxes
36

III.
Tree emissions of soil‐produced CH4
40

IV.
Tree‐produced CH4
42

V.
Trees in forest CH4 budgets
44

VI.
Conclusions
46

Acknowledgements
48

Author contributions
48

References
48

Forest ecosystem methane (CH4) research has focused on soils, but trees are also important sources and sinks in forest CH4 budgets. Living and dead trees transport and emit CH4 produced in soils; living trees and dead wood emit CH4 produced inside trees by microorganisms; and trees produce CH4 through an abiotic photochemical process. Here, we review the state of the science on the production, consumption, transport, and emission of CH4 by living and dead trees, and the spatial and temporal dynamics of these processes across hydrologic gradients inclusive of wetland and upland ecosystems. Emerging research demonstrates that tree CH4 emissions can significantly increase the source strength of wetland forests, and modestly decrease the sink strength of upland forests. Scaling from stem or leaf measurements to trees or forests is limited by knowledge of the mechanisms by which trees transport soil‐produced CH4, microbial processes produce and oxidize CH4 inside trees, a lack of mechanistic models, the diffuse nature of forest CH4 fluxes, complex overlap between sources and sinks, and extreme variation across individuals. Understanding the complex processes that regulate CH4 source–sink dynamics in trees and forests requires cross‐disciplinary research and new conceptual models that transcend the traditional binary classification of wetland vs upland forest.
Using the Occupational Information Network (O*NET) to demonstrate the importance of understanding statistics for undergraduate students
Authors: Crisostomo Marisa E. , Chauhan Rahul S.
Published: December 2018

Because of the increasing use of business analytics to improve business processes, it is not difficult to argue the importance that undergraduate business students gain the ability to understand, interpret, and communicate statistics. However, a task that may be difficult for statistics instructors is to quickly demonstrate and convince business students the importance of statistics. This paper presents an assignment that utilizes the Occupational Information Network (O*NET) to demonstrate the importance of understanding basic statistical concepts such as population parameters, sampling methods, descriptive measures, and displaying data. This can be administered to an introductory business statistics course in order to drum up students' initial interest and views of applicability of statistics.
Low Order Modeling for Fan and Outlet Guide Vanes in Aero-Engines
Authors: Cui Jiahuan , Watson Rob , Ma Yunfei , Tucker Paul
Published: December 2018

Intakes of reduced length have been proposed with the aim of producing aero-engines with higher efficiency and reduced weight. As the intake length decreases, it is expected that stronger effects of the fan on the flow over the intake lip will be seen. If the effects of the fan cannot be ignored, a low-cost but still accurate fan model is of great importance for designing a short-intake. In this paper, a low order rotor/stator model, the immersed boundary method with smeared geometry (IBMSG), has been further developed and validated on a rig test case. The improved IBMSG is more robust than the original. The rig test case used for validation features a low-pressure compression system with a nonaxisymmetric inflow, which is representative of the inlet condition of an aero-engine at its cruise condition. Both the fan and the outlet guide vanes (OGVs) are modeled using IBMSG. A detailed analysis is carried out on the flow both upstream and downstream of the fan. After validating the IBMSG method against the rig test case, a short-intake case, coupled with a fan designed for the next generation of aero-engines, is further investigated. It is found that compared with the intake-alone case, the inflow distortion at the fan face is significantly reduced by the presence of fan. Due to this increased interaction between the fan and the flow over the intake lip, accounting for the effects of the downstream fan is shown to be essential when designing a short intake.
Echo statistics associated with discrete scatterers: A tutorial on physics-based methods
Authors: Stanton Timothy K. , Lee Wu-Jung , Baik Kyungmin
Published: December 2018

When a beam emitted from an active monostatic sensor system sweeps across a volume, the echoes from scatterers present will fluctuate from ping to ping due to various interference phenomena and statistical processes. Observations of these fluctuations can be used, in combination with models, to infer properties of the scatterers such as numerical density. Modeling the fluctuations can also help predict system performance and associated uncertainties in expected echoes. This tutorial focuses on “physics-based statistics,” which is a predictive form of modeling the fluctuations. The modeling is based principally on the physics of the scattering by individual scatterers, addition of echoes from randomized multiple scatterers, system effects involving the beampattern and signal type, and signal theory including matched filter processing. Some consideration is also given to environment-specific effects such as the presence of boundaries and heterogeneities in the medium. Although the modeling was inspired by applications of sonar in the field of underwater acoustics, the material is presented in a general form, and involving only scalar fields. Therefore, it is broadly applicable to other areas such as medical ultrasound, non-destructive acoustic testing, in-air acoustics, as well as radar and lasers.
An Oculus Rift Assessment of Dynamic Balance by Head Mobility in a Virtual Park Scene: A Pilot Study
Authors: Lubetzky Anat V. , Hujsak Bryan D. , Fu Gene , Perlin Ken
Published: December 2018

Postural sway does not differentiate between balance disorders. Head kinematics within a salient, immersive environment could potentially help identifying movement patterns that are unique to vestibular dysfunction. We describe a virtual park scene, where participants are asked to avoid a virtual ball approaching their head, to target dynamic balance and quantify head movement strategy. Sixteen patients with vestibular dysfunction and 16 healthy controls were wearing the Oculus Rift and performed the “park” scene on floor and stability trainers. Significant between-group differences emerged in head path (patients rotated their head sideways more), head acceleration (controls had higher acceleration, especially on translation movements), and peak frequency (controls peaked around the frequency of the ball whereas patients were variable). Those findings demonstrated good to excellent test–retest reliability. There were no significant between-group differences in postural sway parameters. Future studies should establish norms across different levels of balance dysfunction and investigate the underlying mechanism leading to the movement strategy observed.
A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic lateral sclerosis
Authors: Maier Marcel , Welt Tobias , Wirth Fabian , Montrasio Fabio , Preisig Daniel , McAfoose Jordan , Vieira Fernando G. , Kulic Luka , Späni Claudia , Stehle Thilo , Perrin Steve , Weber Markus , Hock Christoph , Nitsch Roger M. , Grimm Jan
Published: December 2018

A human-derived antibody that is selective for misfolded SOD1 decreases motor impairments and boosts survival in several rodent models of ALS.
Wireless, battery-free, flexible, miniaturized dosimeters monitor exposure to solar radiation and to light for phototherapy
Authors: Heo Seung Yun , Kim Jeonghyun , Gutruf Philipp , Banks Anthony , Wei Pinghung , Pielak Rafal , Balooch Guive , Shi Yunzhou , Araki Hitoshi , Rollo Derrick , Gaede Carey , Patel Manish , Kwak Jean Won , Peña-Alcántara Amnahir E. , Lee Kyu-Tae , Yun Yeojeong , Robinson June K. , Xu Shuai , Rogers John A.
Published: December 2018

Wireless, battery-free, flexible dosimeters measure personalized exposure to electromagnetic radiation outdoors and in clinical environments.
The virtue of tolerance
Authors: Shen Keyue
Published: December 2018

A chromatin-inspired nanodrug suppresses undesired immune responses.
Modeling Prevention of Malaria and Selection of Drug Resistance with Different Dosing Schedules of Dihydroartemisinin-Piperaquine Preventive Therapy during Pregnancy in Uganda
Authors: Wallender Erika , Zhang Nan , Conrad Melissa , Kakuru Abel , Muhindo Mary , Tumwebaze Patrick , Kajubi Richard , Mota Daniel , Legac Jennifer , Jagannathan Prasanna , Havlir Diane , Kamya Moses , Dorsey Grant , Aweeka Francesca , Rosenthal Philip J. , Savic Rada M.
Published: December 2018

Dihydroartemisinin-piperaquine (DHA-PQ) is under study for intermittent preventive treatment during pregnancy (IPTp), but it may accelerate selection for drug resistance. Understanding the relationships between piperaquine concentration, prevention of parasitemia, and selection for decreased drug sensitivity can inform control policies and optimization of DHA-PQ dosing.
Role of the Hydrophobic Bridge in the Carbapenemase Activity of Class D β-Lactamases
Authors: Stewart Nichole K. , Smith Clyde A. , Antunes Nuno T. , Toth Marta , Vakulenko Sergei B.
Published: December 2018

Class D carbapenemases are enzymes of the utmost clinical importance due to their ability to confer resistance to the last-resort carbapenem antibiotics. We investigated the role of the conserved hydrophobic bridge in the carbapenemase activity of OXA-23, the major carbapenemase of the important pathogen
Acinetobacter baumannii
.
Persistent Infection and Long-Term Carriage of Typhoidal and Nontyphoidal Salmonellae
Authors: Gal-Mor Ohad
Published: December 2018

The ability of pathogenic bacteria to affect higher organisms and cause disease is one of the most dramatic properties of microorganisms. Some pathogens can establish transient colonization only, but others are capable of infecting their host for many years or even for a lifetime.
Cross-sectional and prospective follow-up study to detect early signs of cardiac dysfunction in obesity: protocol of the CARDIOBESE study
Authors: Snelder Sanne M , de Groot - de Laat Lotte E , Biter L Ulas , Castro Cabezas Manuel , van de Geijn Gert-Jan , Birnie Erwin , Boxma - de Klerk Bianca , Klaassen René A , Zijlstra Felix , van Dalen Bas M
Published: December 2018

Introduction

In view of the increasing occurrence of both obesity and heart failure, a growing overlap of these two clinical entities in the near future is expected. Significant advances in our understanding of the pathophysiological consequences of obesity for the cardiovascular system have been made over the past two decades. However, to optimise management and treatment of obesity patients, further research is required to improve early identification of cardiac dysfunction in obesity and to gain insight in the underlying pathophysiology. The CARdiac Dysfunction In OBesity – Early Signs Evaluation (CARDIOBESE) study has been designed to address these issues.

Methods and analysis

CARDIOBESE is a cross-sectional multicentre study of 100 obesity patients scheduled for bariatric surgery (body mass index (BMI) ≥35 kg/m2) without known cardiovascular disease, and 50 age-matched and gender-matched non-obese controls (BMI <30 kg/m2). Echocardiography, blood and urine biomarkers and Holter monitoring will be used to identify parameters that are able to show cardiac dysfunction at a very early stage in obesity patients (primary objective). Furthermore, a prospective follow-up study of obesity patients before and 1 year after bariatric surgery will be done to gain insight in the pathophysiology of obesity causing cardiac dysfunction (secondary objective).

Ethics and dissemination

The study was approved by the Medical Ethics Committee Toetsingscommissie Wetenschappelijk Onderzoek Rotterdam e.o. (TWOR). Inclusion of patients and controls is almost complete. Analyses of the investigations are currently being performed, and dissemination through peer-reviewed publications and conference presentations is expected from the first quarter of 2019. By identifying early markers of cardiac dysfunction in obesity, and by understanding the underlying pathophysiology of the abnormalities of these markers, the CARDIOBESE study may provide guidance for risk stratification, monitoring and treatment strategies for obesity patients.
From ED overcrowding to jail overcrowding: a cautionary tale of a Serial Inebriate Programme (SIP)
Authors: Navarro Ignacio , Anglemyer Andrew
Published: December 2018

Introduction

Community-based programmes have been implemented to curtail ED use by individuals with chronic public intoxication. Among these programmes is the Serial Inebriate Programme (SIP), which aims to reduce use of ED and emergency medical services. We present the results of an evaluation of the SIP in Santa Cruz, California, including data on the participants’ police and jail history, information not considered in prior analyses of SIPs.

Methods

In the present study, we used a retrospective cohort to evaluate the effectiveness of the SIP in Santa Cruz, California from 2013 to 2015. Specifically, we looked at the programme effects on participants’ arrests, nights in jail, use of the local ED and ambulance services after programme adjudication.

Results

The median number of visits to the ED for participants before and after adjudication was reduced from 4 to 1, and participants showed a significant decrease in their number of jail bookings following adjudication (−4.5 bookings; p=0.004). However, the average number of nights in jail served by participants after adjudication was 2.1 times the average number of nights spent in jail spent before programme adjudication (58.5 vs 27.6 nights in jail for postadjudication and preadjudication groups, respectively; p=0.009).

Conclusions

Our findings suggest that the Santa Cruz SIP had some impact in reducing participants’ use of emergency services, but at the cost of increased jail time. The burdens of placing chronically intoxicated individuals in jail for extended periods of time are not trivial and should not be overlooked when designing and implementing a SIP.
Sample sizes based on three popular indices of risks
Authors: Wang Hongyue , Wang Bokai , Tu Xin M , Liu Jinyuan , Feng Changyong
Published: December 2018

Sample size justification is a very crucial part in the design of clinical trials. In this paper, the authors derive a new formula to calculate the sample size for a binary outcome given one of the three popular indices of risk difference. The sample size based on the absolute difference is the fundamental one, which can be easily used to derive sample size given the risk ratio or OR.
Clocks in the clinic: circadian rhythms in health and disease
Authors: Kelly Rachael M , Healy Ultan , Sreenan Seamus , McDermott John H , Coogan Andrew N
Published: December 2018

Circadian rhythms are endogenously generated recurring patterns of around 24 hours with well-established roles in physiology and behaviour. These circadian clocks are important in both the aetiology and treatment of various psychiatric and metabolic diseases. To maintain physiological homeostasis and optimal functioning, living life synchronised to these clocks is desirable; modern society, however, promotes a ‘24/7’ lifestyle where activity often occurs during the body’s ‘biological night’, resulting in mistimed sleep and circadian misalignment. This circadian desynchrony can increase the risk of disease and can also influence treatment response. Clinicians should be aware of the influence that circadian desynchrony can have on health and disease, in order to potentially develop new therapeutic strategies and to incorporate chronotherapeutics into current treatment strategies to enhance their utility.
Workforce requirements in rheumatology: a systematic literature review informing the development of a workforce prediction risk of bias tool and the EULAR points to consider
Authors: Unger Julia , Putrik Polina , Buttgereit Frank , Aletaha Daniel , Bianchi Gerolamo , Bijlsma Johannes W J , Boonen Annelies , Cikes Nada , Dias João Madruga , Falzon Louise , Finckh Axel , Gossec Laure , Kvien Tore K , Matteson Eric L , Sivera Francisca , Stamm Tanja A , Szekanecz Zoltan , Wiek Dieter , Zink Angela , Dejaco Christian , Ramiro Sofia
Published: December 2018

Objective

To summarise the available information on physician workforce modelling, to develop a rheumatology workforce prediction risk of bias tool and to apply it to existing studies in rheumatology.

Methods

A systematic literature review (SLR) was performed in key electronic databases (1946–2017) comprising an update of an SLR in rheumatology and a hierarchical SLR in other medical fields. Data on the type of workforce prediction models and the factors considered in the models were extracted. Key general as well as specific need/demand and supply factors for workforce calculation in rheumatology were identified. The workforce prediction risk of bias tool was developed and applied to existing workforce studies in rheumatology.

Results

In total, 14 studies in rheumatology and 10 studies in other medical fields were included. Studies used a variety of prediction models based on a heterogeneous set of need/demand and/or supply factors. Only two studies attempted empirical validation of the prediction quality of the model. Based on evidence and consensus, the newly developed risk of bias tool includes 21 factors (general, need/demand and supply). The majority of studies revealed high or moderate risk of bias for most of the factors.

Conclusions

The existing evidence on workforce prediction in rheumatology is scarce, heterogeneous and at moderate or high risk of bias. The new risk of bias tool should enable future evaluation of workforce prediction studies. This review informs the European League Against Rheumatism points to consider for the conduction of workforce requirement studies in rheumatology.
EULAR ‘points to consider’ for the conduction of workforce requirement studies in rheumatology
Authors: Dejaco Christian , Putrik Polina , Unger Julia , Aletaha Daniel , Bianchi Gerolamo , Bijlsma Johannes W , Boonen Annelies , Cikes Nada , Finckh Axel , Gossec Laure , Kvien Tore K , Madruga Dias Joao , Matteson Eric L , Sivera Francisca , Stamm Tanja A , Szekanecz Zoltan , Wiek Dieter , Zink Angela , Ramiro Sofia , Buttgereit Frank
Published: December 2018

Objective

Current methods used for forecasting workforce requirements in rheumatology are disparate, as are the parameters incorporated into workforce projection studies. The objective of these European League Against Rheumatism (EULAR points to consider (PTC) is to guide future workforce studies in adult rheumatology in order to produce valid and reliable manpower estimates.

Methods

The EULAR Standardised Operating Procedures were followed. A multidisciplinary task force with experts including patients with rheumatic diseases from 11 EULAR countries and the USA was assembled. A systematic literature review (SLR) was conducted to retrieve workforce models in rheumatology and other medical fields. PTC were based on expert opinion informed by the SLR, followed by group discussions with consensus obtained through informal voting. The level of agreement with the PTC was voted anonymously.

Results

A total of 10 PTC were formulated. The task force recommends models integrating supply (=workforce available in rheumatology), demand (=health services requested by the population) and need (=health services that are considered appropriate to serve the population). In general, projections of workforce requirements should consider all factors relevant for current and future workload in rheumatology inside and outside of direct patient care. Forecasts of workforce supply should consider demography and attrition of rheumatologists, as well as the effects of new developments in healthcare. Predictions of future need/demand should take demographic, sociocultural and epidemiological development of the population into account.

Conclusion

These EULAR-endorsed PTC will provide guidance on the methodology and the parameters to be applied in future national and international workforce requirement studies in rheumatology.
Variability of fluid administration during exploratory laparotomy for abdominal trauma
Authors: Baker Jennifer E , Martin Grace E , Katsaros Gianna , Lewis Hannah V , Wakefield Connor J , Josephs Sean A , Nomellini Vanessa , Makley Amy T , Goodman Michael D
Published: December 2018

Background

Approximately 8% of traumatically injured patients require transfusion with packed red blood cells (pRBC) and only 1% to 2% require massive transfusion. Intraoperative massive transfusion was defined as requiring greater than 5 units (u) of pRBC in 4 hours. Despite the majority of patients not requiring transfusion, the appropriate amount and type of crystalloid administered during the era of damage control resuscitation have not been analyzed. We sought to determine the types of crystalloid used during trauma laparotomies and the potential effects on resuscitation.

Methods

Patients who underwent laparotomy after abdominal trauma from January 2014 to December 2016 at the University of Cincinnati Medical Center were identified. Patients were grouped based on requiring 0u, 1u to 4u, and ≥5u pRBC during intraoperative resuscitation. Demographic, physiologic, pharmacologic, operative, and postoperative data were collected. Statistical analysis was performed with Kruskal-Wallis test and Pearson’s correlation coefficient.

Results

Lactated Ringer’s (LR) solution was the most used crystalloid type received in the 0u and 1u to 4u pRBC cohorts, whereas normal saline (NS) was the most common in the ≥5u pRBC cohort. Most patients received two types of crystalloid intraoperatively. NS and LR were most frequently the first crystalloids administered, with Normosol infusion occurring later. The amount of crystalloid received correlated with operative length, but did not correlate with the estimated blood loss. Neither the type of crystalloid administered nor the anesthesia provider type was associated with changes in postoperative resuscitation parameters or electrolyte concentrations.

Discussion

There is a wide variation in the amount and types of crystalloids administered during exploratory laparotomy for trauma. Interestingly, the amount or type of crystalloid given did not affect resuscitation parameters regardless of blood product requirement.

Level of evidence

Level IV.
Fermented Red Ginseng Alleviates Cyclophosphamide-Induced Immunosuppression and 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis in Mice by Regulating Macrophage Activation and T Cell Differentiation
Authors: Kim Jeon-Kyung , Kim Jae-Young , Jang Se-Eun , Choi Min-Sun , Jang Hyo-Min , Yoo Hae-Hyun , Kim Dong-Hyun
Published: December 2018

A variety of products have been developed with red ginseng (RG, the steamed roots of Panax ginseng Meyer). To clarify the immunomodulating effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), enzyme-treated eRG (ERG) and probiotic-fermented eRG (FRG), we examined their immunopotentiating and immunosuppressive effects in mice with cyclophosphamide (CP)-induced immunosuppression (CI) or 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis (TC). Oral administration of RG in CI mice significantly increased blood IFN-[Formula: see text] levels. Treatment with RG also increased the tumoricidal effects of CI mouse splenic cytotoxic T (Tc) and NK cells against YAC-1 cells. Treatment with RGs, in particular FRG and wRG, significantly increased Th1 cell differentiation. Treatment with RG except wRG increased Treg cell differentiation. However, wRG alone increased IL-6 and IL-17 expression in the colon of CI mice. Furthermore, RG alleviated colitis in TC mice. FRG most potently suppressed TNBS-induced colon shortening, NF-[Formula: see text]B activation and TNF-[Formula: see text] and IL-17 expression and increased IL-10 expression. RGs inhibited TNF-[Formula: see text] expression and increased IL-10 expression in lipopolysaccharide-stimulated primary macrophages in vitro while the differentiation of splenic T cells into type 1 T (Th1) and regulatory T (Treg) cells was increased by FRG in vitro. In conclusion, FRG can alleviate immunosuppression and inflammation by inhibiting macrophage activation and regulating Th1 and Treg cell differentiation.
Comfort Decision Modeling
Authors: Engemann Kurt J. , Yager Ronald R.
Published: December 2018

We introduce comfort decision modeling for decision problems in which an alternative is to be selected based on a measure of satisfaction we refer to as comfort. We define comfort as the difference between the payoff received by selecting a particular strategy and the worst payoff that could have been received under the manifestation of the same state-of-nature. We define the effective comfort associated with an alternative as the aggregation of an alternative’s comforts across all possible states-of-nature. We study several methods of aggregating an alternative’s individual comforts across the different states-of-nature, incorporating various types of information about the uncertainty associated with the states-of-nature. We provide a Comfort Decision Model to determine the value of alternatives utilizing attitudinal measures of the decision maker. We demonstrate a process of performing sensitivity of the resulting decision to a measure of the attitude of the decision maker. Lastly, we use an illustration to show the practicability and cogency of the new method.
Differential quenching of the angular momentum of the B and Q bands of a porphyrin as a result of extended ring π-conjugation
Authors: Hooper Riley W. , Zhang Angel , Koszelewski Dominik , Lewtak Jan P. , Koszarna Beata , Levy Christopher J. , Gryko Daniel T. , Stillman Martin J.
Published: December 2018

A novel porphyrin, whose [Formula: see text]-system has been extended via the presence of two additional carbon–carbon triple bonds on opposite meso-positions and by fusion of a single naphthalene unit simultaneously bridging the third meso-position and the [Formula: see text]-carbon of one of the pyrroles, has been synthesized in good yield. Absorption, magnetic circular dichroism, emission, and theoretical spectra are reported for the fused and unfused trans-naphthalene free base and zinc porphyrins. The fusing of one of the naphthalene moieties results in significant changes to the absorption spectrum and, very unusually, the bridged meso-[Formula: see text]-pyrrole fusion results in quenching of the MCD Faraday pseudo-A term in the porphyrin’s B band (S2). This unique effect was interpreted as resulting from the origin of the electronic structure of the second excited state (the B state). The [Formula: see text] and [Formula: see text] polarizations are completely mixed by the electronic effects of the non-symmetric extended conjugation of the [Formula: see text] ring. Analysis of the origin of the MCD signal indicates that the presence of this novel mixed polarization leads to negligible angular momentum in the important B state. To our knowledge, this is the first report in which the magnetic moment in a porphyrin’s intensely absorbing B band has been quenched while the angular momentum in the Q band, the first excited state, remains as normal. This implies that the photophysical properties of the B state are likely very different than those of the Q state, which has novel and significant implications for applications, especially in non-linear spectroscopy.
Investigating ion release using inline ICP during in situ scratch testing of an Mg-Li(-Al-Y-Zr) alloy
Authors: Yan Yuanming , Zhou Peng , Gharbi Oumaïma , Zeng Zhuoran , Chen Xiaobo , Volovitch Polina , Ogle Kevin , Birbilis Nick
Published: December 2018

An electrochemical flow cell was constructed to permit the application of a mechanical scratch to the exposed material while monitoring the open circuit dissolution rates of the elemental alloy components. Elemental dissolution rates were determined where measured downstream using inductively coupled plasma atomic emission spectrometry (ICP-AES). The technique is demonstrated with Mg-Li(-Al-Y-Zr) alloy exposed to 0.01 M NaCl. A mechanical scratch was applied manually using a non-conductive and non-contaminating sapphire lancet without interrupting the on-line measurement. The ion dissolution rate from the newly exposed surface was significantly higher than the dissolution rate from the remaining surface area, corresponding to a high local current density. Notably, the increase in the dissolution rate from the scratched area occurred gradually after the scratch; then subsided within 200 s after the scratch, indicating that this particular Mg-alloy can repassivate by the formation of a surface film after a scratch was applied. This is the first reported use of an in situ scratch cell coupled with operando ICP-AES.
Overexpression of IL-11 promotes premalignant gastric epithelial hyperplasia in isolation from germline gp130-JAK-STAT driver mutations
Authors: Buzzelli Jon N. , O’Connor Louise , Scurr Michelle , Chung Nien Chin Sharleen , Catubig Angelique , Ng Garrett Z. , Oshima Masanobu , Oshima Hiroko , Giraud Andrew S. , Sutton Philip , Judd Louise M. , Menheniott Trevelyan R.
Published: December 2018

Expression of the cytokine IL-11 is elevated in human Helicobacter pylori infection and progressively increases with worsening gastric pathology. Additionally, IL-11 is required for tumor development in STAT3-dependent murine models of gastric cancer (GC) and, when administered acutely, causes resolving atrophic gastritis. However, it is unclear whether locally elevated IL-11 ligand expression can, in isolation from oncogenic gp130-JAK-STAT pathway mutations, initiate GC pathogenesis. Here we developed a transgenic mouse model of stomach-specific (keratin 19 promoter) IL-11 ligand overexpression. Keratin 19 promoter-IL-11 transgenic ( K19-IL11Tg) mice showed specific IL-11 overexpression in gastric corpus and antrum but not elsewhere in the gastrointestinal tract or in other tissues. K19-IL11Tgmice developed spontaneous premalignant disease of the gastric epithelium, progressing from atrophic gastritis to TFF2-positive metaplasia and severe epithelial hyperplasia, including adenoma-like lesions in a subset of older (1 yr old) animals. Although locally advanced, the hyperplastic lesions remained noninvasive. H. pylori infection in K19-IL11Tgmice accelerated some aspects of the premalignant phenotype. Finally, K19-IL11Tgmice had splenomegaly in association with elevated serum IL-11, with spleens showing an expanded myeloid compartment. Our results provide direct in vivo functional evidence that stomach-specific overexpression of IL-11, in isolation from germline gp130-JAK-STAT3 genetic drivers, is sufficient for premalignant progression. These findings have important functional implications for human GC, in which frequent IL-11 overexpression occurs in the reported absence of somatic mutations in gp130 signaling components.

NEW & NOTEWORTHY We provide direct in vivo functional evidence that stomach-specific overexpression of the cytokine IL-11, in isolation from gp130-JAK-STAT3 pathway mutations, can trigger spontaneous atrophic gastritis progressing to locally advanced epithelial hyperplasia (but not dysplasia or carcinoma), which does not require, but may be accelerated by, concomitant Helicobacter pylori infection.
RNA regulons are essential in intestinal homeostasis
Authors: Parham Louis R. , Williams Patrick A. , Chatterji Priya , Whelan Kelly A. , Hamilton Kathryn E.
Published: December 2018

Intestinal epithelial cells are among the most rapidly proliferating cell types in the human body. There are several different subtypes of epithelial cells, each with unique functional roles in responding to the ever-changing environment. The epithelium’s ability for rapid and customized responses to environmental changes requires multitiered levels of gene regulation. An emerging paradigm in gastrointestinal epithelial cells is the regulation of functionally related mRNA families, or regulons, via RNA-binding proteins (RBPs). RBPs represent a rapid and efficient mechanism to regulate gene expression and cell function. In this review, we will provide an overview of intestinal epithelial RBPs and how they contribute specifically to intestinal epithelial stem cell dynamics. In addition, we will highlight key gaps in knowledge in the global understanding of RBPs in gastrointestinal physiology as an opportunity for future studies.
Ventilatory responses to acute hypoxia and hypercapnia in humans with a patent foramen ovale
Authors: Davis James T. , Boulet Lindsey M. , Hardin Alyssa M. , Chang Alex J. , Lovering Andrew T. , Foster Glen E.
Published: December 2018

Subjects with a patent foramen ovale (PFO) have blunted ventilatory acclimatization to high altitude compared with subjects without PFO. The blunted response observed could be because of differences in central and/or peripheral respiratory chemoreflexes. We hypothesized that compared with subjects without a PFO (PFO−), subjects with a PFO (PFO+) would have blunted ventilatory responses to acute hypoxia and hypercapnia. Sixteen PFO+ subjects (9 female) and 15 PFO− subjects (8 female) completed four 20-min trials on the same day: 1) normoxic hypercapnia (NH), 2) hyperoxic hypercapnia (HH), 3) isocapnic hypoxia (IH), and 4) poikilocapnic hypoxia (PH). Hypercapnic trials were completed before the hypoxic trials, the order of the hypercapnic (NH & HH) and hypoxic (IH & PH) trials were randomized, and trials were separated by ≥40 min. During the NH trials but not the HH trials subjects who were PFO+ had a blunted hypercapnic ventilatory response compared with subjects who were PFO− (1.41 ± 0.46 l·min−1·mmHg−1 vs. 1.98 ± 0.71 l·min−1·mmHg−1, P = 0.02). There were no differences between the PFO+ and PFO− subjects with respect to the acute hypoxic ventilatory response during IH and PH trials. Hypoxic ventilatory depression was similar between subjects who were PFO+ and PFO− during IH. These data suggest that compared with subjects who were PFO−, subjects who were PFO+ have normal ventilatory chemosensitivity to acute hypoxia but blunted ventilatory chemosensitivity to carbon dioxide, possibly because of reduced carbon dioxide sensitivity of either the central and/or the peripheral chemoreceptors.

NEW & NOTEWORTHY Patent foramen ovale (PFO) is found in ~25%–40% of the population. The presence of a PFO appears to be associated with blunted ventilatory responses during acute exposure to normoxic hypercapnia. The reason for this blunted ventilatory response during acute exposure to normoxic hypercapnia is unknown but may suggest differences in either central and/or peripheral chemoreflex contribution to hypercapnia.
Rapamycin and FTY720 Alleviate Atherosclerosis by Cross Talk of Macrophage Polarization and Autophagy
Authors: Sun Rui-zhen , Fan Ying , Liang Xiao , Gong Tian-tian , Wang Qi , Liu Hui , Shan Zhi-yan , Lei Lei
Published: December 2018

Foam cell formation and macrophage polarization are involved in the pathologic development of atherosclerosis, one of the most important human diseases affecting large and medium artery walls. This study was designed to assess the effects of rapamycin and FTY720 (fingolimod) on macrophages and foam cells. Mouse peritoneal macrophages were collected and treated with rapamycin and FTY720 to study autophagy, polarization, and lipid accumulation. Next, foam cells were formed by oxidizing low-density lipoprotein to observe changes in lipid accumulation, autophagy, and polarization in rapamycin-treated or FTY720-treated foam cells. Lastly, foam cells that had been treated with rapamycin and FTY720 were evaluated for sphingosine 1-phosphate receptor (S1prs) expression. Autophagy microtubule-associated protein 1 light chain 3- (LC3-) II was increased, and classically activated macrophage phenotype markers interleukin- (IL-) 6, cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS) were increased, whereas alternatively activated macrophage phenotype markers transforming growth factor- (TGF-)β, arginase 1 (Arg1), and mannose receptor C-type 1 (Mrc1) were decreased by rapamycin in peritoneal macrophages. LC3-II was also obviously enhanced, though polarization markers were unchanged in rapamycin-treated foam cells. Moreover, lipid accumulation was inhibited in rapamycin-treated macrophage cells but was unchanged in rapamycin-treated foam cells. For FTY720, LC3-II did not change, whereas TGF-β, Arg1 and Mrc1 were augmented, and IL-6 was suppressed in macrophages. However, LC3-II was increased, and TGF-β, ARG1 and MRC1 were strikingly augmented, whereas IL-6, COX2 and iNOS could be suppressed in foam cells. Furthermore, lipid accumulation was alleviated in FTY720-treated foam cells. Additionally, S1pr1 was markedly decreased in foam cells (P< .05); S1pr2, S1pr3, S1pr4 and S1pr5 were unchanged in rapamycin-treated foam cells. In FTY720-treated foam cells, S1pr3 and S1pr4 were decreased, and S1pr1, S1pr2 and S1pr5 were unchanged. Therefore, we deduced that rapamycin stimulated classically activated macrophages and supressed early atherosclerosis. Rapamycin may also stabilize artery plaques by preventing apoptosis and S1PR1 in advanced atherosclerosis. FTY720 allowed transformation of foam cells into alternatively activated macrophages through the autophagy pathway to alleviate advanced atherosclerosis.