bluuebunny/crossref_metadata_2025 huggingface dataset:
757 Mass Casualty Planning, When an Airplane Strikes a Building
Authors: Kearns Randy D , Carter Jeffrey E
Published: March 2020

Introduction

This paper focuses on the risks associated with the rapid development of aviation as well as the rapid growth of high-rise or large capacity buildings. The aim of the work is to further evaluate the incidence of building strikes involving aircraft. With this scenario, a burn injury is the most common for survivors. This paper will examine the nature and frequency of these events. Knowing the risks can aid the planning effort for all involved with a role in the response to a mass casualty incident.

Methods

The researchers reviewed historical records involving airplane crashes into large occupied buildings. This review included databases searched such as PubMed as well as commonly used search engines; Google and Bing. Inclusion criteria for buildings included those either considered mid-rise or high-rise (typically considered taller than 33 meters [108 feet]) or a large footprint (defined as 5000 square meters [54820 square feet]). Furthermore, the buildings had to be occupied.

The airplanes included civilian (commercial) and military aircraft. The literature reviewed included historical accounts and historical references from a variety of news archival services that were chronicled in articles published and indexed in the PubMed search engine or found in common historical databases. The search also included the National Transportation Safety Board (NTSB) reports.

Results

Once the descriptive data were collected, the information was analyzed for similarities and trended where applicable. A total of 19 of the aircraft impacts were analyzed for this work. While death tolls were included in the results collected, the work aimed to identify the number of injured patients, and where possible, further identify those with burn injuries. All of the crashes also included the distance to the closest metro area (typically where a burn center was or should be located.) It should be noted that all of the buildings impacted were located within 50 kilometers (31 miles) of an airport with many of them occurring on or adjacent to airport property.

Conclusions

It is reasonable to presume that commercial or military aircraft that impact large occupied buildings such as a commercial complex, high-rise housing or an office building will produce disastrous consequences. This scenario includes significant casualties and loss of life. Findings from this research can offer insights from actual occurrences to disaster planners and emergency managers.

Applicability of Research to Practice

Mass casualty planning for burn centers should include the potential impact by aircraft and either large or high rise buildings. The size of the incident could be significant and the potential for the occurrence should not be overlooked.
Embryonic development and fecundity of the red deep-sea crab Chaceon quinquedens (Smith, 1879) (Decapoda: Brachyura: Geryonidae) in the Mid-Atlantic Bight determined by image analysis
Authors: Martínez-Rivera Stephanie , Stevens Bradley G
Published: March 2020

The red deep-sea crab, Chaceon quinquedens (Smith, 1879), has been harvested from the US Atlantic continental shelf since the 1970s, but knowledge about its biology is extremely limited. We describe the stages and seasonality of embryonic development and determine size-specific fecundity for C. quinquedens in the Mid-Atlantic Bight. Samples were collected by trawling aboard research vessels in 2012–2013, and from traps aboard commercial fishing vessels in 2014–2016. Four stages of embryonic development were described: 1) early development, 2) mid-development, 3) late development, and 4) hatching. A relationship between embryonic development stage and egg-mass color was observed. A brooding cycle was proposed after analyzing seasonal changes in the stages of embryonic development. Fecundity was estimated by using an automated imaging method for egg samples during stage 1 and 2. The estimates of fecundity, the number of eggs per brood, ranged from 34,691 to 324,729 for females between 62.6 and 106.2 mm in carapace length (CL). The linear regression showed a positive correlation between fecundity and female body size in CL (R2 = 0.56). This study provides information on reproductive parameters needed to improve fisheries management.
Effects of Extreme Low Winter Temperatures on the Overwintering Survival of the Introduced Larval Parasitoids Spathius galinae and Tetrastichus planipennisi: Implications for Biological Control of Emerald Ash Borer in North America
Authors: Duan Jian J , Bauer Leah S , Van Driesche Roy , Schmude Jonathan M , Petrice Toby , Chandler Jennifer L , Elkinton Joe
Published: March 2020

Climate change has been linked to shifts in the distribution and phenology of species although little is known about the potential effects that extreme low winter temperatures may have on insect host–parasitoid interactions. In late January 2019, northern regions of the United States experienced a severe cold wave caused by a weakened jet stream, destabilizing the Arctic polar vortex. Approximately 3 mo later at six study sites in southern Michigan and three in southern Connecticut, we sampled the overwintering larvae of the emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), and two larval parasitoids, Spathius galinae (Hymenoptera: Braconidae) and Tetrastichus planipennisi (Hymenoptera: Eulophidae), that are being introduced as emerald ash borer biocontrol agents in North America. At these nine study sites, emerald ash borer-infested ash trees and/or saplings were debarked and each overwintering emerald ash borer and parasitoid larva was then examined for cold-induced mortality, as indicated by a brown coloration, flaccid, and watery consistency. In early spring in Michigan, we found 4.5–26% of emerald ash borer larvae, 18–50% of S. galinae larvae, and 8–35% of T. planipennisi larvae were killed by cold. In Connecticut where temperatures were more moderate than in Michigan during the 2019 cold wave, <2% of the larval hosts and parasitoids died from cold injury. Our findings revealed that cold-induced mortality of overwintering larvae of emerald ash borer and its larval parasitoids varied by location and species, with higher mortality of parasitoid larvae in most Michigan sites compared to host larvae. The potential impacts of our findings on the management of emerald ash borer using biocontrol are discussed.
Hidden Politics? Assessing Lobbying Success During US Agency Guidance Development
Authors: Yackee Susan Webb
Published: March 2020

I test the proposition that interest groups achieve greater policy success when they lobby during the agency guidance document development process as opposed to the notice and comment process. Policymaking via guidance documents often receives lower levels of public attention, which provides greater flexibility to accommodate lobbying requests. I analyze the hypothesis during the creation of 41 rules by one US government agency—20 of which were promulgated using the notice and comment process and 21 via the guidance document process. I measure regulatory policy change using a content analysis of government documents and lobbying texts, and I also incorporate a telephone survey of interest groups who lobbied on these same rules. I find that interest groups perceive—and achieve—greater policy success when lobbying during the agency guidance process. The results yield new insights into the relationship between lobbying and regulatory policymaking.
Effect of X-ray dose rates higher than 8 Gy/min on the functioning of cardiac implantable electronic devices
Authors: Nakamura Kazuhiko , Aoyama Takahiro , Kaneda Naoki , Otsuji Masashi , Minami Yoshitaka , Sakuragi Ami , Nakamura Masaru
Published: March 2020

Direct irradiation may cause malfunctioning of cardiac implantable electronic devices (CIEDs). Therefore, a treatment plan that does not involve direct irradiation of CIEDs should be formulated. However, CIEDs may be directly exposed to radiation because of the sudden intrafractional movement of the patient. The probability of CIED malfunction reportedly depends on the dose rate; however, reports are only limited to dose rates ≤8 Gy/min. The purpose of this study was to investigate the effect of X-ray dose rates >8 Gy/min on CIED function. Four CIEDs were placed at the center of the radiation field and irradiated using 6 MV X-ray with flattening filter free (6 MV FFF) and 10 MV X-ray with flattening filter free (10 MV FFF). The dose rate was 4–14 Gy/min for the 6 MV FFF and 4–24 Gy/min for 10 MV FFF beams. CIED operation was evaluated with an electrocardiogram during each irradiation. Three CIEDs malfunctioned in the 6 MV FFF condition, and all four CIEDs malfunctioned in the 10 MV FFF condition, when the dose rate was >8 Gy/min. Pacing inhibition was the malfunction observed in all four CIEDs. Malfunction occurred simultaneously along with irradiation and simultaneously returned to normal function on stopping the irradiation. An X-ray dose rate >8 Gy/min caused a temporary malfunction due to interference. Therefore, clinicians should be aware of the risk of malfunction and manage patient movement when an X-ray dose rate >8 Gy/min is used for patients with CIEDs.
Self-full ceers and the uniform join operator
Authors: Andrews Uri , Schweber Noah , Sorbi Andrea
Published: March 2020

A computably enumerable equivalence relation (ceer) $X$ is called self-full if whenever $f$ is a reduction of $X$ to $X$, then the range of $f$ intersects all $X$-equivalence classes. It is known that the infinite self-full ceers properly contain the dark ceers, i.e. the infinite ceers which do not admit an infinite computably enumerable transversal. Unlike the collection of dark ceers, which are closed under the operation of uniform join, we answer a question from [ 4] by showing that there are self-full ceers $X$ and $Y$ so that their uniform join $X\oplus Y$ is non-self-full. We then define and examine the hereditarily self-full ceers, which are the self-full ceers $X$ so that for any self-full $Y$, $X\oplus Y$ is also self-full: we show that they are closed under uniform join and that every non-universal degree in ${\operatorname{\textbf{Ceers}}}_{\operatorname{{\mathcal{I}}}}$ have infinitely many incomparable hereditarily self-full strong minimal covers. In particular, every non-universal ceer is bounded by a hereditarily self-full ceer. Thus, the hereditarily self-full ceers form a properly intermediate class in between the dark ceers and the infinite self-full ceers, which is closed under $\oplus $.
Axion structure formation – II. The wrath of collapse
Authors: Lentz Erik W , Quinn Thomas R , Rosenberg Leslie J
Published: March 2020

The first paper in this series showed that quantum chromodynamic axion dark matter, as a highly correlated Bose fluid, contains extra-classical physics on cosmological scales. The source of the derived extra-classical physics is exchange–correlation interactions induced by the constraints of symmetric particle exchange and interaxion correlations from self-gravitation. The paper also showed that the impact of extra-classical physics on early structure formation is marginal, as the exchange–correlation interaction is inherently non-linear. This paper continues the study of axion structure formation into the non-linear regime, considering the case of full collapse and virialization. The N-body method is chosen to study the collapse, and its algorithms are derived for a condensed Bose fluid. Simulations of isolated gravitational collapse are performed for both Bose and cold dark matter fluids using a prototype N-body code. Unique Bose structures are found to survive even the most violent collapses. Bose post-collapse features include dynamical changes to global structures, creation of new broad sub-structures, violations of classical binding energy conditions, and new fine structures. Effective models of the novel structures are constructed and possibilities for their observation are discussed.
CCD VI time-series of the extremely metal-poor globular cluster M92: revisiting its variable star population
Authors: Yepez M A , Arellano Ferro A , Deras D
Published: March 2020

We present an analysis of VI CCD time-series photometry of the Oo II type globular cluster M92. The variable star population of the cluster is studied with the aim of revising their classifications, identifications, frequency spectra, and to select indicators of the parental cluster metallicity and distance. The Fourier decomposition of RR Lyrae light curves lead to the estimation of mean [Fe/H]spec = −2.20 ± 0.18 and distance of 8.3 ± 0.2 kpc. Four new variables are reported: one RRd (V40), a multimode SX Phe (V41), an SR (V42), and one RRc (F1) that is most likely not a cluster member. The AC nature of V7 is confirmed. The double mode nature of the RRc star V11 is not confirmed and its amplitude modulations are most likely due to the Blazhko effect. Two modes are found in the known RRc variable V13. It is argued that the variable V30, previously classified as RRab is, in fact, a BL Her-type star not belonging to the cluster. Using the Gaia-DR2 proper motions, we identified 5012 stars in the field of the cluster, which are very likely cluster members, and for which we possess photometry, enabling the production of a refined colour–magnitude diagram. This also allowed us to identify a few variable stars that do not belong to the cluster. The RR Lyrae pulsation modes on the HB are cleanly separated by the first overtone red edge, a common feature in all Oo II-type clusters.
Resonant capture in quadruple stellar systems
Authors: Tremaine Scott
Published: March 2020

Some quadruple star systems in the hierarchical 2 + 2 configuration exhibit orbit–orbit resonances between the two compact binaries. We show that the most important resonances occur at period ratios of 1:1, 3:2, and 2:1. We describe the conditions required for capture and show that they can be satisfied at the 3:2 and 2:1 resonances in binaries that migrate significantly in semimajor axis after circularization, probably through magnetic braking or gravitational radiation.
A comprehensive study of open clusters Czernik 14, Haffner 14, Haffner 17 and King 10 using multicolour photometry and Gaia DR2 astrometry
Authors: Bisht D , Zhu Qingfeng , Yadav R K S , Durgapal Alok , Rangwal Geeta
Published: March 2020

This paper presents an investigation into the four open clusters Czernik 14, Haffner 14, Haffner 17 and King 10, located near the Perseus arm of the Milky Way, using the Gaia DR2, 2MASS, WISE, APASS and Pan-STARRS1 data sets. We find normal interstellar extinction in 12 photometric bands for these clusters. Using Gaia DR2 proper motion data, the numbers of likely cluster members are found to be 225, 353, 350 and 395 for Czernik 14, Haffner 14, Haffner 17 and King 10, respectively. Radii are determined as 3.5, 3.7, 6.2 and 5.7 arcmin for Czernik 14, Haffner 14, Haffner 17 and King 10, respectively. Mean proper motions in RA and Dec. are estimated as (−0.42 ± 0.02, −0.38 ± 0.01), (−1.82 ± 0.009, 1.73 ± 0.008), (−1.17 ± 0.007, 1.88 ± 0.006) and (−2.75 ± 0.008, −2.04 ± 0.006) mas yr−1 for Czernik 14, Haffner 14, Haffner 17 and King 10, respectively. The comparison of observed colour–magnitude diagrams with solar metallicity isochrones leads to ages of 570 ± 60, 320 ± 35, 90 ± 10 and 45 ± 5 Myr for these clusters. The distances of 2.9 ± 0.1, 4.8 ± 0.4, 3.6 ± 0.1 and 3.8 ± 0.1 kpc determined using parallax are similar to the values derived by the isochrone-fitting method. Mass function slopes are found to be in good agreement with the Salpeter value. The total masses are derived as 348, 595, 763 and 1088 M⊙ for Czernik 14, Haffner 14, Haffner 17 and King 10, respectively. Evidence for the existence of a mass-segregation effect is observed in each cluster. Using the Galactic potential model, Galactic orbits are derived for the clusters. It is found that all four clusters follow a circular path around the Galactic Centre.
C–C motif chemokine receptor 2 as a novel intermediate in the ovulatory cascade
Authors: Jaworski JP , Urrutia M , Dascal E , Jaita G , Peluffo MC
Published: March 2020

Expression of immune function genes within follicle cells has been reported in ovaries from many species. Recent work from our laboratory showed a direct effect of the monocyte chemoattractant protein 1/C-C motif chemokine receptor 2 system within the feline cumulus oocyte complex, by increasing the mRNA levels of key genes involved in the ovulatory cascade in vitro. Studies were designed to evaluate if C–C motif chemokine receptor 2 acts as a novel mediator of the ovulatory cascade in vitro. Therefore, feline cumulus oocyte complexes were cultured in the presence or absence of a highly selective C–C motif chemokine receptor 2 antagonist together with known inducers of cumulus–oocyte expansion and/or oocyte maturation to assess mRNA expression of key genes related to periovulatory events in other species as well as oocyte maturation. Also, the effects of recombinant monocyte chemoattractant protein 1 on spontaneous or gonadotrophin-induced oocyte maturation were assessed. This is an in vitro system using isolated cumulus oocyte complexes from feline ovaries. The present study reveals the modulation of several key ovulatory genes by a highly selective C–C motif chemokine receptor 2 antagonist. However, this antagonist was not enough to block the oocyte maturation induced by gonadotropins or amphiregulin. Nonetheless, recombinant monocyte chemoattractant protein 1 had a significant effect on spontaneous oocyte maturation, increasing the percentage of metaphase II stage oocytes in comparison to the control. This is the first study in any species to establish C–C motif chemokine receptor 2 as a mediator of some actions of the mid-cycle gonadotrophin surge.
Acute kidney injury in renal transplant recipients undergoing cardiac surgery
Authors: Hundemer Gregory L , Srivastava Anand , Jacob Kirolos A , Krishnasamudram Neeraja , Ahmed Salman , Boerger Emily , Sharma Shreyak , Pokharel Kapil K , Hirji Sameer A , Pelletier Marc , Safa Kassem , Kulvichit Win , Kellum John A , Riella Leonardo V , Leaf David E
Published: March 2020

Background

Acute kidney injury (AKI) is a key risk factor for chronic kidney disease in the general population, but has not been investigated in detail among renal transplant recipients (RTRs). We investigated the incidence, severity and risk factors for AKI following cardiac surgery among RTRs compared with non-RTRs with otherwise similar clinical characteristics.

Methods

We conducted a retrospective cohort study of RTRs (n = 83) and non-RTRs (n = 83) who underwent cardiac surgery at two major academic medical centers. Non-RTRs were matched 1:1 to RTRs by age, preoperative (preop) estimated glomerular filtration rate and type of cardiac surgery. We defined AKI according to Kidney Disease: Improving Global Outcomes criteria.

Results

RTRs had a higher rate of AKI following cardiac surgery compared with non-RTRs [46% versus 28%; adjusted odds ratio 2.77 (95% confidence interval 1.36–5.64)]. Among RTRs, deceased donor (DD) versus living donor (LD) status, as well as higher versus lower preop calcineurin inhibitor (CNI) trough levels, were associated with higher rates of AKI (57% versus 33% among DD-RTRs versus LD-RTRs; P = 0.047; 73% versus 36% among RTRs with higher versus lower CNI trough levels, P = 0.02). The combination of both risk factors (DD status and higher CNI trough level) had an additive effect (88% AKI incidence among patients with both risk factors versus 25% incidence among RTRs with neither risk factor, P = 0.004).

Conclusions

RTRs have a higher risk of AKI following cardiac surgery compared with non-RTRs with otherwise similar characteristics. Among RTRs, DD-RTRs and those with higher preop CNI trough levels are at the highest risk.
MYB–bHLH–TTG1 Regulates Arabidopsis Seed Coat Biosynthesis Pathways Directly and Indirectly via Multiple Tiers of Transcription Factors
Authors: Li Song Feng , Allen Patrick J , Napoli Ross S , Browne Richard G , Pham Hanh , Parish Roger W
Published: March 2020

MYB–bHLH–WDR (MBW) transcription factor (TF) complexes regulate Arabidopsis seed coat development including mucilage and tannin biosynthesis. The R2R3 MYBs MYB5, MYB23 and TRANSPARENT TESTA2 (TT2) participate in the MBW complexes with the WD-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). These complexes regulate GLABRA2 (GL2) and TTG2 expression in developing seeds. Microarray transcriptome analysis of ttg1-1- and wild-type (Ler) developing seeds identified 246 TTG1-regulated genes, which include all known metabolic genes of the tannin biosynthetic pathway. The first detailed TTG1-dependent metabolic pathways could be proposed for the biosynthesis of mucilage, jasmonic acid (JA) and cuticle including wax ester in developing seeds. We also assigned many known and previously uncharacterized genes to the activation/inactivation of hormones, plant immunity and nutrient transport. The promoters of six cuticle pathway genes were active in developing seeds. Expression of 11 genes was determined in the developing seeds of the combinatorial mutants of MYB5, MYB23 and TT2, and in the combinatorial mutants of GL2, HOMEODOMAIN GLABROUS2 (HDG2) and TTG2. These six TFs positively co-regulated the expression of four repressor genes while three of the six TFs repressed the wax biosynthesis genes examined, suggesting that the three TFs upregulate the expression of these repressor genes, which, in turn, repress the wax biosynthesis genes. Chromatin immunoprecipitation analysis identified 21 genes directly regulated by MYB5 including GL2, HDG2, TTG2, four repressor genes and various metabolic genes. We propose a multi-tiered regulatory mechanism by which MBWs regulate tannin, mucilage, JA and cuticle biosynthetic pathways.
On Non-Eliminative Structuralism. Unlabeled Graphs as a Case Study, Part B†
Authors: Leitgeb Hannes
Published: March 2020

This is Part B of an article that defends non-eliminative structuralism about mathematics by means of a concrete case study: a theory of unlabeled graphs. Part A motivated an understanding of unlabeled graphs as structures sui generis and developed a corresponding axiomatic theory of unlabeled graphs. Part B turns to the philosophical interpretation and assessment of the theory: it points out how the theory avoids well-known problems concerning identity, objecthood, and reference that have been attributed to non-eliminative structuralism. The part concludes by explaining how the theory relates to set theory, and what remains to be accomplished for non-eliminative structuralists.
Epistemic Judgement and Motivation
Authors: Boult Cameron , Köhler Sebastian
Published: March 2020

Is there an epistemic analogue of moral motivational internalism? The answer to this question has implications for our understanding of the nature of epistemic normativity. For example, some philosophers have argued from claims that epistemic judgement is not necessarily motivating to the view that epistemic judgement is not normative. This paper examines the options for spelling out an epistemic analogue of moral motivational internalism. It is argued that the most promising approach connects epistemic judgements to doxastic dispositions, which are related to motivation in a fairly tenuous sense. It is also argued that this approach currently lacks a plausible and informative account of the nature and workings of these doxastic dispositions, and, hence, an explanation of the range of phenomena internalist theses typically set out to explain. The most promising route for developing such an account, based on recent expressivist work, is investigated and found inadequate for the task.
DARE to be different? A novel approach for analysing diversity in collaborative research projects
Authors: Bone Frédérique , Hopkins Michael M , Ràfols Ismael , Molas-Gallart Jordi , Tang Puay , Davey Gail , Carr Antony M
Published: March 2020

Growth in collaborative research raises difficulties for those tasked with research evaluation, particularly in situations where outcomes are slow to emerge. This article presents the ‘Diversity Approach to Research Evaluation’ (DARE) as a novel way to assess how researchers engaged in knowledge creation and application work together as teams. DARE provides two important insights: first, it reveals the differences in background and experience between individual team members that can make research collaboration both valuable and challenging; second, DARE provides early insights into how team members are working together. DARE achieves these insights by analysing team diversity and cohesiveness in five dimensions, building on Boschma’s multi-dimensional concept of proximity. The method we propose combines narratives, maps, and indicators to facilitate the study of research collaboration. The article introduces the DARE method and pilots an initial operationalization through the study of two grant-funded biomedical research projects led by researchers in the UK. Suggestions for further development of the approach are discussed.
Policy Inertia, Election Uncertainty, and Incumbency Disadvantage of Political Parties
Authors: Chatterjee Satyajit , Eyigungor Burcu
Published: March 2020

We document that postwar U.S. elections show a strong pattern of “incumbency disadvantage”: if a party has held the presidency of the country or the governorship of a state for some time, that party tends to lose popularity in the subsequent election. We show that this fact can be explained by a combination of policy inertia and unpredictability in election outcomes. A quantitative analysis shows that the observed magnitude of incumbency disadvantage can arise in several different models of policy inertia. Normative and positive implications of policy inertia leading to incumbency disadvantage are explored.
Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy
Authors: Li Caiyu , Wang Xue , Bi Yajuan , Yu Heshui , Wei Jing , Zhang Yi , Han Lifeng , Zhang Youcai
Published: March 2020

Organic anion transporters 1 and 3 (OAT1 and OAT3) play a critical role in renal drug-drug interactions and are involved in the nephrotoxicity of many anionic xenobiotics. To date, relatively little is known about the interaction of natural compounds with OAT1 and OAT3. Of the 270 natural compounds screened in the present study, 21 compounds inhibited OAT1 and 45 compounds inhibited OAT3. Further concentration-dependent studies identified 7 OAT1 inhibitors and 10 OAT3 inhibitors with IC50 values of <10 μM, and most of them were flavonoids, the most commonly ingested polyphenolic compounds in the diet and herbal products. Computational modeling of OAT1 and OAT3 revealed the important residues for the recognition of inhibitors. The two strong OAT inhibitors, namely wedelolactone and wogonin, were evaluated for their in vivo interactions with the OAT substrate aristolochic acid I (AAI), a natural compound causing aristolochic acid-induced nephropathy (AAN) in many species. The cytotoxicity of AAI increased in two OAT-overexpressing cell lines, with more cytotoxicity in OAT1-overexpressing cells, suggesting a more important role of OAT1 than OAT3 in AAN. Both wedelolactone and wogonin markedly increased serum AAI concentrations in AAI-treated rats and ameliorated kidney injuries in AAI-treated mice. To conclude, the present findings are of significant value in understanding natural compound-drug interactions and provide a natural source for developing treatments for AAN.
Development of an Improved T-cell Assay to Assess the Intrinsic Immunogenicity of Haptenic Compounds
Authors: Ogese Monday O , Watkinson Joel , Lister Adam , Faulkner Lee , Gibson Andrew , Hillegas Aimee , Sakatis Melanie Z , Park Brian Kevin , Naisbitt Dean J
Published: March 2020

The prediction of drug hypersensitivity is difficult due to the lack of appropriate models and known risk factors. In vitro naïve T-cell priming assays that assess immunogenicity have been developed. However, their application is limited due requirements for 2 batches of autologous dendritic cells (DC) and inconsistent results; a consequence of single well readouts when exploring reactions where compound-specific T-cell frequency is undefined. Hence, we aimed to develop an improved, but simplified assay, termed the T-cell multiple well assay (T-MWA), that permits assessment of drug-specific activation of naïve T cells, alongside analysis of the strength of the induced response and the number of cultures that respond. DC naïve T-cell coculture, depleted of regulatory T cells (Tregs), was conducted in up to 48 wells for 2 weeks with model haptens (nitroso sulfamethoxazole [SMX-NO], Bandrowski’s base [BB], or piperacillin [PIP]). Cultures were rechallenged with hapten and T-cell proliferation was measured using [3H]-thymidine incorporation. Priming of naïve T cells was observed with SMX-NO, with no requirement for DC during restimulation. Greater than 65% of cultures were activated with SMX-NO; with 8.0%, 30.8%, and 27.2% characterized as weak (stimulation index [SI] =1.5–1.9), moderate (SI = 2–3.9), and strong responses (SI > 4), respectively. The number of responding cultures and strength of the response was reproducible when separate blood donations were compared. Coinhibitory checkpoint blockade increased the strength of the proliferative response, but not the number of responding cultures. Moderate to strong priming responses were detected with BB, whereas PIP stimulated only a small number of cultures to proliferate weakly. In drug-responsive cultures inducible CD4+CD25+FoxP3+CD127low Tregs were also identified. To conclude, the T-MWA offers improvements over existing assays and with development it could be used to study multiple HLA-typed donors in a single plate format.
Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing
Authors: Li Xilin , Chen Si , Guo Xiaoqing , Wu Qiangen , Seo Ji-Eun , Guo Lei , Manjanatha Mugimane G , Zhou Tong , Witt Kristine L , Mei Nan
Published: March 2020

Metabolism plays a key role in chemical genotoxicity; however, most mammalian cells used for in vitro genotoxicity testing lack effective metabolizing enzymes. We recently developed a battery of TK6-derived cell lines that individually overexpress 1 of 8 cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, and 3A4) using a lentiviral expression system. The increased expression and metabolic function of each individual CYP in each established cell line were confirmed using real-time PCR, Western blotting, and mass spectrometry analysis; the parental TK6 cells and empty vector (EV) transduced cells had negligible CYP levels. Subsequently, we evaluated these cell lines using 2 prototypical polyaromatic hydrocarbon mutagens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P), that require metabolic activation to exert their genotoxicity. DMBA-induced cytotoxicity, phosphorylation of histone H2A.X, and micronucleus formation were significantly increased in TK6 cells with CYP1A1, 1B1, 2B6, and 2C19 expression as compared with EV controls. B[a]P significantly increased cytotoxicity, DNA damage, and chromosomal damage in TK6 cells overexpressing CYP1A1 and 1B1 when compared with EV controls. B[a]P also induced micronucleus formation in TK6 cells expressing CYP1A2. These results suggest that our CYP-expressing TK6 cell system can be used to detect the genotoxicity of compounds requiring metabolic transformation.
Factors Associated With the Use of Supervised Consumption Facilities Among Women Who Inject Drugs in a Canadian Setting
Authors: Ickowicz Sarah , Grant Cameron , Nosova Ekaterina , Boyd Jade , Brar Rupinder , Milloy M.-J. , Hayashi Kanna , Nolan Seonaid
Published: March 2020

Background:

Supervised consumption facilities (SCFs) are evidence-based harm reduction interventions that have been shown to reduce the risk of social and health-related harms associated with injection drug use. Previous qualitative studies have highlighted important motivations for SCF use among women who use drugs. However, factors associated with SCF use among women have not previously been evaluated.

Methods:

Data were obtained from 2 longitudinal community-recruited cohorts of people who use drugs in Vancouver, Canada between 2003 and 2017. Multivariable generalized estimating equations were used to calculate the odds of SCF use associated with social and structural risk factors for drug-related harm among women who reported injection drug use in the preceding 6-months.

Results:

A total of 795 participants were included in the study, contributing to 6302 interviews, with 602 participants (76%) reporting SCF use in at least one interview. Multivariable analysis demonstrated daily heroin and crystal methamphetamine injection (Adjusted Odds Ratio [AOR] = 1.32 and 1.65, respectively), injecting in public (AOR = 1.77), binge injection (AOR = 1.22) and lack of housing (AOR = 1.74) to be associated with SCF use.

Conclusions:

The current study demonstrates higher intensity patterns of drug use, including daily heroin and crystal methamphetamine injection, injecting in public and binge injection, as well as homelessness to be associated with SCF use among women. Future research should identify barriers to SCF use among women to minimize the risk of overdose and other drug-related harms.
Practice Makes Transfer Imperfect: Evidence From Auditory Learning
Authors: Zaltz Yael , Kishon-Rabin Liat , Karni Avi , Ari-Even Roth Daphne
Published: March 2020

Background:

Evidence from motor and visual studies suggests that the ability to generalize learning gains to untrained conditions decreases as the training progresses. This decrease in generalization was suggested to reflect a shift from higher to lower levels of neuronal representations of the task following prolonged training. In the auditory modality, however, the few studies that tested the influence of prolonging training on generalization ability showed no decrease and sometimes even an increase in generalization.

Objective:

To test the impact of extending training in a basic psychoacoustic task on the ability to generalize the gains attained in training to untrained conditions.

Design:

Eighty-two young adults participated in two experiments that differed in the specific training regimen. In both experiments, training was conducted using a difference limen for frequency (DLF) task with an adaptive forced-choice procedure, for either a single- or nine-session training. Following training, generalization to the untrained ear and to an untrained frequency was assessed.

Results:

(a) Training induced significant learning (i.e., smaller DLF thresholds) following a single session of training, and more so following nine training sessions; (b) results from the combined data from both experiments showed that the ability to generalize the learning gains to the untrained ear and frequency was limited after the extended DLF training; (c) larger improvements under the trained condition resulted in smaller generalization to the untrained conditions.

Conclusions:

The findings of increased specificity with training in the auditory modality support the notion that gradual changes, both quantitative and qualitative, occur in the neural representations of an auditory task during its acquisition. These findings suggest common underlying mechanisms in basic skill learning across different modalities.
Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals
Authors: Leisman Daniel E. , Harhay Michael O. , Lederer David J. , Abramson Michael , Adjei Alex A. , Bakker Jan , Ballas Zuhair K. , Barreiro Esther , Bell Scott C. , Bellomo Rinaldo , Bernstein Jonathan A. , Branson Richard D. , Brusasco Vito , Chalmers James D. , Chokroverty Sudhansu , Citerio Giuseppe , Collop Nancy A. , Cooke Colin R. , Crapo James D. , Donaldson Gavin , Fitzgerald Dominic A. , Grainger Emma , Hale Lauren , Herth Felix J. , Kochanek Patrick M. , Marks Guy , Moorman J. Randall , Ost David E. , Schatz Michael , Sheikh Aziz , Smyth Alan R. , Stewart Iain , Stewart Paul W. , Swenson Erik R. , Szymusiak Ronald , Teboul Jean-Louis , Vincent Jean-Louis , Wedzicha Jadwiga A. , Maslove David M.
Published: March 2020

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of “modifiable risk factors”, measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.
Preference for vigorous exercise versus sedentary sucrose drinking: an animal model of anergia induced by dopamine receptor antagonism
Authors: Correa Mercè , Pardo Marta , Carratalá-Ros Carla , Martínez-Verdú Andrea , Salamone John D.
Published: March 2020

Motivation has activational and directional components. Mesolimbic dopamine is critical for the regulation of behavioral activation and effort-related processes in motivated behaviors. Impairing mesolimbic dopamine function leads to fatigue and anergia, but leaves intact other aspects of reinforce seeking behaviors, such as the consummatory or hedonic component. In male Swiss mice, we characterized the impact of dopamine antagonism on the selection of concurrently presented stimuli that have different vigor requirements. We analyzed running wheel activity versus sucrose solution intake, typically used as a measure of anhedonia. Results are compared with data from nonconcurrent presentation to those stimuli. In the concurrent presentation experiment, control mice preferred to spend time running compared to sucrose intake. Dopamine antagonism shifted relative reinforcer preference, reducing time spent on the running wheel, but actually increasing time-consuming sucrose. Mice increased frequency of bouts for both reinforcers, suggesting that there was fatigue in the running wheel rather than aversion. Moreover, satiation or habituation by preexposing animals to both reinforcers did not shift preferences. In the nonconcurrent experiments, haloperidol reduced running wheel but had no impact on sucrose consumption. Dopamine antagonism did not change preference for sucrose or total volume consumed. Additional correlational analyses indicated that baseline differences in sucrose consumption were independent of baseline running or novelty exploration. Thus, dopamine antagonism seems to have anergic rather than anhedonic effects, and the concurrent presentation in this setting could be useful for assessing preferences based on effort requirements.
Parent cognitive, behavioural, and affective factors and their relation to child pain and functioning in pediatric chronic pain: a systematic review and meta-analysis
Authors: Donnelly Theresa J. , Palermo Tonya M. , Newton-John Toby R.O.
Published: March 2020

Previous studies have demonstrated that parental cognitive, behavioral, and emotional factors are related to child functioning in children and adolescents with chronic pain. This is particularly important to understand how to potentially enhance the efficacy of psychological interventions for children by incorporating interventions targeting parents. We conducted a systematic review and meta-analysis to identify the specific parent factors that have been examined in the literature and to quantify the associations observed between parent factors and child pain and disability. A search of the electronic databases EMBASE, PsychINFO, Medline, and PubMed was conducted, using search terms related to chronic pain, pediatric population, and parents. Fifty-four studies met criteria and were included in the review. Parent pain catastrophizing and protective behavior were the most commonly assessed parental constructs in the literature. Meta-analyses were conducted for associations between parent pain catastrophizing, parent protective behaviors, parent anxiety and depression, and parent stress associated with parenting a child with chronic pain with child pain, disability, school functioning, and emotional functioning. Correlation coefficients were pooled using the random-effects model. A medium relationship was observed between higher protective behavior and poorer school functioning (r = −0.39), and small relationships were found between higher parent pain catastrophizing and increased child disability (r = 0.29); higher protective behaviors and increased child disability (r = 0.25); and increased parent depression and anxiety with increased child disability (r = 0.23 and r = 0.24, respectively). Future research is needed to investigate broader parent variables and overcome methodological weaknesses in this field.
Assessment and Interpretation of Vitamin and Trace Element Status in Sick Children
Authors:   ESPGHAN Committee on Nutrition, Gerasimidis Konstantinos , Bronsky Jiri , Catchpole Anthony , Embleton Nicholas , Fewtrell Mary , Hojsak Iva , Indrio Flavia , Hulst Jessie , Köglmeier Jutta , de Koning Barbara , Lapillonne Alexandre , Molgaard Christian , Moltu Sissel Jennifer , Norsa Lorenzo , Verduci Elvira , Domellöf Magnus
Published: March 2020

Assessment of vitamin and trace element status (VTE) is important in the clinical management of the sick child. In this position paper, we present the various assessment methods available to the clinical practitioner, and critically discuss pitfalls with interpretation of their results. There are 4 main approaches to assess the VTE body status of an individual patient including clinical examination, dietary assessment, and measurement of direct and indirect biomarkers of VTE in biological samples. Clinical signs of VTE deficiencies usually present only when body stores are substantially depleted and are often difficult to detect or differentiate from other nonnutrient‐related causes. In isolation, dietary assessment of micronutrients can be inaccurate and imprecise, in disease and in individual patient assessment but may be useful to complement findings from other VTE assessment methods. Use of biomarkers is the most common approach to assess VTE status in routine practice but in the presence of systemic inflammatory response and in the absence of appropriate paediatric reference intervals, interpretation of biomarker results might be challenging and potentially mislead clinical practice. The use of a multimodal approach, including clinical examination, dietary assessment, and laboratory biomarkers is proposed as the optimal way to ascertain the VTE status of individual patients. In the presence of acute inflammatory conditions, VTE measurements in plasma should be replaced by biomarkers not affected by systemic inflammatory response or delayed until inflammatory state is resolved.
Patterns of Primary, Specialty, Urgent Care, and Emergency Department Care in Children With Inflammatory Bowel Diseases
Authors: Michel Hilary K. , Noll Robert B. , Siripong Nalyn , Kim Sandra C.
Published: March 2020

Objectives:

Pediatric patients with inflammatory bowel diseases (IBD) require treatment, monitoring, and health maintenance services. We described patterns of primary, specialty, emergency department (ED) and urgent care delivery, and explored patient‐ and system‐related variables that impact ED/urgent care utilization.

Methods:

We conducted a cross sectional survey of parents of children with IBD at a large tertiary children's hospital.

Results:

One hundred sixty‐one parents completed the survey (75% response). Mean patient age 13.9 years (51% boys); 80% Crohn disease, 16% ulcerative colitis, 4% IBD‐unspecified. Mean disease duration 4 years (standard deviation [SD] 2.7). Thirty percent had at least 1 other chronic disease, 31% had a history of IBD‐related surgery. Parents were predominantly Caucasian (94%), well‐educated (61% bachelor's degree/higher), part of a 2‐parent household (79%) living in a suburban setting (57%). Seventy‐seven percent of patients had private insurance. In the past year, most children had 1 to 2 IBD‐related office visits (54%) with their gastroenterology (GI) doctor and no IBD‐related hospitalizations (79%). Eighty‐eight percent (N = 141) had a primary care provider (PCP), and most (70%) saw their PCP 1 to 2 times. Even so, 86% (N = 139) received medical care from places other than their PCP or GI doctor; 27% in the ED and 45% at urgent care. Children of parents with less than a bachelor's degree, families that lived further from their GI doctor, and children who saw their PCP more often were more likely to utilize ED/urgent care.

Conclusions:

ED/urgent care utilization in pediatric patients with IBD was greater than expected, potentially contributing to fragmented, costly care and worse outcomes.
Deficits in Bone Architecture and Strength in Children Living With HIV on Antiretroviral Therapy
Authors: Shiau Stephanie , Yin Michael T. , Strehlau Renate , Burke Megan , Patel Faeezah , Kuhn Louise , Coovadia Ashraf , Norris Shane A. , Arpadi Stephen M. ,   Changes Bone Study Team
Published: March 2020

Background:

Reduced bone mineral mass by dual x-ray absorptiometry is reported in children living with HIV (CLWH), but few studies of bone microarchitecture, particularly in sub-Saharan Africa, have been conducted. Here, we compare bone architecture and strength in black South African CLWH and uninfected control children by peripheral quantitative computed tomography (pQCT).

Setting and Methods:

One hundred seventy-two CLWH on antiretroviral therapy (ART) and 98 controls in the CHANGES Bone Study in Johannesburg, South Africa received pQCT scans of the radius and tibia. Measurements included trabecular and cortical volumetric bone mineral density (vBMD) and bone strength, estimated by the polar strength strain index (SSI), a validated measure of fracture risk.

Results:

CLWH (51% boys) and controls (63% boys) were an average of age 10.4 years. Mean ART duration for CLWH was 9.5 years, with 70.9% on an efavirenz-based, 28.5% on a lopinavir/ritonavir-based, and 1 child on an atazanavir/ritonavir-based regimen. Male CLWH had lower trabecular vBMD at the radius than controls after adjustment for age, radial length, and Tanner stage (β = −17.3, standard error = 7.2, P = 0.018). Bone strength by polar SSI was lower in CLWH than controls (778 vs. 972 mm3, P < 0.01). CLWH on an LPV/r-based regimen had lower trabecular vBMD (199 vs. 222 mg/cm3, P < 0.001) and cortical vBMD (1074 vs. 1093 mg/cm3, P = 0.004) than those on an efavirenz-based regimen. No difference in bone strength by polar SSI was observed between treatment groups.

Conclusion:

CLWH initiated on ART early in life with well-controlled HIV have deficits in bone architecture and reductions in bone strength as detected by pQCT.