bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional tissue stiffness mapping in the mouse embryo supports durotaxis during early limb bud morphogenesis
Authors: Zhu Min , Tao Hirotaka , Samani Mohammad , Luo Mengxi , Wang Xian , Hopyan Sevan , Sun Yu
Published: September 2018

Numerous biophysical hypotheses invoke tissue stiffness as a key parameter for shaping tissue during development and for influencing cell behaviours during disease progression. However, currently available methods are insufficient to test hypotheses that concern the physical properties of bulk tissues. Here we introduce, validate and apply a new 3D magnetic device that generates a uniform magnetic field gradient within a space that is sufficient to accommodate a vertebrate, organ-stage embryo under live conditions. The device allows for rapid, nontoxic measurement of the spatial variation of absolute elastic modulus and viscosity deep within mesenchymal tissues and within epithelia. By applying the device to map the spatiotemporal variation of viscoelastic properties within the early mouse limb bud, we identified an anteriorly biased mesodermal stiffness gradient along which cells move collectively to shape the early bud. Tissue stiffness corresponds to the nascent expression domain of fibronectin that isWnt5a-dependent. The findings challenge the notion thatWnt5aregulates cell movements by chemotaxis, and raises the possibility thatWnt5amodifies the tissue microenvironment to promote durotaxisin vivo. Importantly, the ability to precisely measure tissue stiffness in 3D has the potential to instigate and refine mechanisms of development and disease progression.
cellHarmony: Cell-level matching and holistic comparison of single-cell transcriptomes
Authors: DePasquale Erica AK , Dexheimer Phillip , Schnell Daniel , Ferchen Kyle , Hay Stuart , Valiente-Alandí Íñigo , Blaxall Burns C. , Grimes H. Leighton , Salomonis Nathan
Published: September 2018

To understand the molecular pathogenesis of human disease, precision analyses to define molecular alterations within (and between) disease-associated cell populations are desperately needed. Single-cell genomics represents an ideal platform to enable the identification and comparison of normal and diseased transcriptional cell states. We note that disease-associated perturbations usually retain cellular-identity programs (core genes), providing an appropriate reference for secondary comparison analyses. Thus, we created cellHarmony, an integrated solution for the unsupervised analysis and classification of cell types from diverse scRNA-Seq datasets. cellHarmony is an automated and easy-to-use tool that efficiently matches single-cell transcriptomes using a community clustering and alignment strategy. Utilizing core genes and community clustering to reveal disease and cell-state systems-level insights overcomes bias toward donor and disease effects that can be imposed by joint-alignment approaches. Moreover, cellHarmony directly compares cell frequencies and gene expression in a cell-type-specific manner, then produces a holistic representation of these differences across potentially dozens of cell populations and impacted regulatory networks. Using this approach, we identify gene regulatory programs that are selectively impacted in distinct hematopoietic and heart cell populations that suggest novel disease mechanisms and drug targets. Thus, this approach holds tremendous promise in revealing the molecular and cellular origins of complex diseases.
A V0-ATPase-dependent apical trafficking pathway maintains the polarity of the intestinal absorptive membrane
Authors: Bidaud-Meynard Aurélien , Nicolle Ophélie , Heck Markus , Michaux Grégoire
Published: September 2018

Intestine function relies on the strong polarity of intestinal epithelial cells and the array of microvilli forming a brush border at their luminal pole. Combining genetic RNAi screen and in vivo super-resolution imaging in the C. elegans intestine, we uncovered that the V0 sector of the V-ATPase (V0-ATPase) controls a late apical trafficking step, involving RAB-11 endosomes and the SNARE SNAP-29, necessary to maintain the polarized localization of both apical polarity modules and brush border proteins. We show that the V0-ATPase pathway also genetically interacts with glycosphingolipids in enterocyte polarity maintenance. Finally, we demonstrate that depletion of the V0-ATPase fully recapitulates the severe structural, polarity and trafficking defects observed in enterocytes from patients with Microvillus inclusion disease (MVID) and used this new in vivo MVID model to follow the dynamics of microvillus inclusions. Hence, we describe a new function for the V0-ATPase in apical trafficking and epithelial polarity maintenance and the promising use of C. elegans intestine as an in vivo model to better understand the molecular mechanisms of rare genetic enteropathies.

Summary statement

V0-ATPase controls a late apical trafficking step involved in the maintenance of the apical absorptive intestinal membrane and its depletion phenocopies the trafficking and structural defects of MVID in C. elegans.
The atypical thiol-disulfide exchange protein α-DsbA2 fromWolbachia pipientisis a homotrimeric disulfide isomerase
Authors: Walden Patricia M. , Lakshmanane Premkumar , Halili Maria , Heras Begoña , King Gordon J. , Whitten Andrew E. , Martin Jennifer L.
Published: September 2018

DiSulfide Bond (DSB) oxidative folding enzymes are master regulators of virulence localized to the periplasm of many Gram-negative bacteria. The archetypal DSB machinery fromEscherichia coliK12 has a dithiol oxidizing redox relay pair (DsbA/B), a disulfide isomerizing redox relay pair (DsbC/D) and specialist reducing enzymes DsbE and DsbG that also interact with DsbD. By contrast the Gram-negative bacteriumWolbachia pipientisencodes just three DSB enzymes. Two of these α-DsbA1 and α-DsbB form a redox relay pair analogous toE. coliDsbA/B. The third enzyme α-DsbA2 incorporates a DsbA-like sequence but does not interact with α-DsbB. In comparison with other DsbA enzymes, α-DsbA2 has ∼50 extra N-terminal residues. The crystal structure of α-DsbA2ΔN, the N-terminally truncated form in which these residues are removed confirms the DsbA-like nature of this domain. However, α-DsbA2 does not have DsbA-like activity: it is structurally and functionally different as a consequence of its N-terminal residues. First, α-DsbA2 is a powerful disulfide isomerase and a poor dithiol oxidase –ieits role is to shuffle rather than introduce disulfide bonds. Moreover, small-angle X-ray scattering of α-DsbA2 reveals a homotrimeric arrangement. Our results allow us to draw conclusions about the factors required for functionally equivalent enzymatic activity across structurally diverse protein architectures.
Epigenomic Profiling and Single-Nucleus-RNA-Seq Reveal Cis-Regulatory Elements in Human Retina, Macula and RPE and Non-Coding Genetic Variation
Authors: Cherry Timothy J. , Yang Marty G. , Harmin David A. , Tao Peter , Timms Andrew E. , Bauwens Miriam , Allikmets Rando , Jones Evan M. , Chen Rui , Baere Elfride De , Greenberg Michael E.
Published: September 2018

Cis-regulatory elements (CREs) orchestrate the dynamic and diverse transcriptional programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. However, the cellular complexity of the human brain has largely precluded the identification of functional regulatory variation within the human CNS. We took advantage of the retina, a well-characterized region of the CNS with reduced cellular heterogeneity, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive resource of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines the regulatory elements with the potential to contribute to mendelian and complex disorders of human vision.
Machine learning models identify multimodal measurements highly predictive of transdiagnostic symptom severity for mood, anhedonia, and anxiety
Authors: Mellem Monika S. , Liu Yuelu , Gonzalez Humberto , Kollada Matthew , Martin William J. , Ahammad Parvez
Published: September 2018

Background:Insights from neuroimaging-based biomarker research have not yet translated into clinical practice. This translational gap could be because of a focus of psychiatric biomarker research on diagnostic classification, rather than on prediction of transdiagnostic psychiatric symptom severity. Currently, no transdiagnostic, multimodal predictive models of symptom severity that include neurobiological characteristics have been described.Methods:We built predictive models of three common symptoms in psychiatric disorders (dysregulated mood, anhedonia, and anxiety) from the Consortium for Neuropsychiatric Phenomics dataset (n=272) which contains clinical scale assessments, resting-state functional-MRI (rs-fMRI) and structural-MRI (sMRI) imaging measures from patients with schizophrenia, bipolar disorder, attention deficit and hyperactivity disorder, and healthy control subjects. We used an efficient, data-driven feature selection approach to identify the most predictive features from these high-dimensional data.Results:This approach optimized modeling and explained 65-90% of variance across the three symptom domains, compared to 22% without using the feature selection approach. The top performing multimodal models retained a high level of interpretability which enabled several clinical and scientific insights. First, to our surprise, structural features did not substantially contribute to the predictive strength of these models. Second, the Temperament and Character Inventory scale emerged as a highly important predictor of symptom variation across diagnoses. Third, predictive rs-fMRI connectivity features were widely distributed across many intrinsic resting-state networks (RSN).Conclusions:Combining rs-fMRI with select questions from clinical scales enabled high levels of prediction of symptom severity across diagnostically distinct patient groups and revealed that connectivity measures beyond a few intrinsic RSNs may carry relevant information for symptom severity.
Public funding, perverse incentives, and counterproductive outcomes
Authors: Volden Gro Holst
Published: September 2018

Purpose

The purpose of this paper is to explore the adverse incentives at the front end of government-funded projects with concentrated benefits and no liabilities for the privileged groups. In particular, the author discusses the risk of perverse incentives of the types typically found in the development aid sector that results in counterproductive outcomes.

Design/methodology/approach

The paper uses a simple conceptual framework based on agency theory. A qualitative, case-based approach with purposive sampling was chosen for the empirical part of the study. Eight Norwegian projects were selected because incentive problems were to be expected, and one development aid project served as a reference case.

Findings

The paper finds that low strategic project success corresponded well with the terms of financing. There were clear indications of agency problems, in three cases to the extent that the incentives turned perverse. The paper concludes with a discussion of relevant measures to prevent the emergence of perverse incentives.

Originality/value

The paper contributes to an improved understanding of the incentives related to public project initiation and selection, which is an under-researched topic and generally not included in formal project governance schemes. The research should therefore be useful to scholars as well as practitioners within the field of project governance.
A link between knowledge sharing and managers’ characteristics
Authors: Matošková Jana , Macurová Lucie , Tomancová Lucie
Published: September 2018

Purpose

The purpose of this paper is to examine whether and to what extent knowledge-oriented leadership (KOL) is associated with knowledge sharing (KS) in an organization as well as the dimensions of this leadership style.

Design/methodology/approach

Opinion-based questionnaires were applied in the study. A principal axis factor analysis was conducted to find the main factors in KOL (n=236). The relationship between KS and KOL was tested with Pearson’s correlation coefficient method.

Findings

The findings support the importance of high-quality leader–member exchange for KS because KOL had a strong significant positive association with the extent of KS in the organization (n=96, r=0.521). The principal axis factor suggested three factors, all of which were moderately significantly related to KS: the perceived support from the superior, enough time for KS and information flow from the superior.

Research limitations/implications

The research design in this study was cross-sectional. Thus, the interpretations of the cause–effect relationship among the variables could not be determined. Furthermore, the findings should be confirmed using a larger sample.

Practical implications

The study indicates that if innovativeness and the use of human capital are important for an organization’s competitive ability, it is vital to train managers to be able to apply KOL.

Originality/value

Few studies have addressed the relationship between leadership and KS. Hence, this study contributes to a better understanding of the relation between KS and KOL style. Additionally, KOL is probably a multidimensional construct, but little empirical work has been done to explore it.
Effect of ingenol mebutate on actinic keratosis in a Korean population: A prospective clinical, dermoscopic and histopathological study from a single center
Authors: Kim Jong Sic , Woo Yu Ri , Kim Miri , Park Hyun Jeong
Published: September 2018

Actinic keratosis (AK) is an in situ squamous cell carcinoma which is mostly found on sun‐damaged skin, and it is prevalent among Caucasians. However, there is a lack of research on evaluating the treatment efficacy of ingenol mebutate (IM) on AK in Asians. This study was intended to analyze the treatment outcomes of IM on AK in Korean patients with regards to clinical, dermoscopic and histopathological aspects. A prospective study on 46 Korean patients who were diagnosed with AK and treated with IM was conducted. Clinically, 80% (24/30) of the patients showed an improvement at 8 weeks. Twenty out of the 30 (66.7%) patients were found to have achieved histopathological clearance. All local skin responses had disappeared at T4 in all patients. Patients with Fitzpatrick skin type III were proven to exhibit better treatment outcomes, both clinically (P = 0.001) and histopathologically (P = 0.001), than those with Fitzpatrick skin type IV. The clinical and histopathological clearance rate of AK with IM in Korean patients was 80% and 66.7%, respectively. The patients with Fitzpatrick skin type IV showed a tendency to have residual AK, histopathologically after treatment with IM. In conclusion, IM could be an effective and safe treatment option on AK in Korean patients. In addition, it would be helpful to carry out a cautious check‐up when treating AK with IM in patients with a darker skin color.
The effect of human capital on occupational health and safety investment: An empirical analysis of Spanish firms
Authors: Nuñez Imanol , Prieto Maite
Published: September 2018

This paper analyses how firms' human capital influences their investments in occupational health and safety (OHS). We argue that the incentive to protect workers by investing in OHS is a function of the stock of human capital. The empirical analysis was based on data from the official Working Conditions Spanish Survey on OHS management. Our sample was restricted to 1,472 firms from the manufacturing and construction industries. Our results show that firms that place more emphasis on training and have a multiskilled and innovative workforce invest more in OHS. However, having technological and design skills has no impact on the investment in OHS, presumably because these skills are widely available in the labour market. Finally, the analysis suggests that some abilities such as problem solving may be affected by informational asymmetries and therefore firms may suboptimally invest in protecting these capabilities.
5‐HT2 and 5‐HT2B antagonists attenuate pro‐fibrotic phenotype in human adult dermal fibroblasts by blocking TGF‐β1 induced non‐canonical signaling pathways including STAT3 : implications for fibrotic diseases like scleroderma
Authors: Chaturvedi Saurabh , Misra Durga Prasanna , Prasad Narayan , Rastogi Kailash , Singh Harshit , Rai Mohit Kumar , Agarwal Vikas
Published: September 2018

Background

Release of 5‐hydroxytryptamine (5‐HT; serotonin) from activated platelets following microvascular injury leads to tissue fibrosis. 5‐HT strongly induces extracellular matrix synthesis in dermal fibroblasts in a transforming growth factor beta 1 (TGF‐β1)‐dependent manner.

Aim

To evaluate anti‐fibrotic properties of inhibitors of 5‐HT2 and 5‐HT2B (terguride, SB204741) respectively in human adult dermal fibroblasts (HADF) derived from a patient with scleroderma.

Methods

Anti‐fibrotic efficacy of 5‐HT2 and 5‐HT2B inhibitors was evaluated as per two strategies: HADF were incubated with 5‐HT (1 μM)/TGF‐β1 (10 ng/mL) for 1 hour followed by 5‐HT (1 μM)/TGF‐β1 (10 ng/mL) and terguride or SB204741 (1 μM, each) for 24 hours (post‐treatment strategy) and HADF were treated with terguride or SB204741 (1 μM, each) for 1 hour followed by 5‐HT (1 μM)/TGF‐β1 (10 ng/mL) for 24 hours (pre‐treatment strategy). Real time quantitative polymerase chain reaction for expression of pro‐fibrotic (TGFΒ1, COL1A1, COL1A2, ACTA2, CTGF and FN1) and anti‐fibrotic genes (MMP2/TIMP1) was performed. Expression of type I collagen, alpha smooth muscle actin (α‐SMA), phosphorylation of Smad3, ERK1/2 and STAT3 was examined by immunoblotting.

Results

Stimulation of HADF cells with 5‐HT/TGF‐β1 led to the increased expression of pro‐fibrotic genes which was significantly reduced by both terguride and SB204741. Expression of anti‐fibrotic genes was not affected upon incubation with the inhibitors. In 5‐HT‐stimulated HADF, treatment with terguride and SB204741 decreased type I collagen and α‐SMA. In 5‐HT/TGF‐β1 stimulated HADF, terguride and SB204741 treatment reduced ERK1/2 and STAT3 phosphorylation but did not influence Smad3 phosphorylation.

Conclusion

Terguride and SB204741 reduce pro‐fibrotic potential of HADF cells and suppress TGF‐β1‐mediated non‐canonical pathways, ERK1/2 and STAT3 which have been implicated in the regulation of pro‐fibrotic genes and in the development of fibrosis. Taken together, our data suggest that 5‐HT inhibitors might reduce fibrosis via suppression of TGF‐beta1‐mediated non‐canonical signaling pathways. These observations have important therapeutic implications for fibrotic disorders like scleroderma.
GMSE: An r package for generalised management strategy evaluation
Authors: Duthie A. Bradley , Cusack Jeremy J. , Jones Isabel L. , Minderman Jeroen , Nilsen Erlend B. , Pozo Rocío A. , Rakotonarivo O. Sarobidy , Van Moorter Bram , Bunnefeld Nils
Published: September 2018

Management strategy evaluation (MSE) is a powerful tool for simulating all key aspects of natural resource management under conditions of uncertainty.

We present the r package generalised management strategy evaluation (GMSE), which applies genetic algorithms to provide a generalised tool for simulating adaptive decision‐making management scenarios between stakeholders with competing objectives under complex social‐ecological interactions and uncertainty.

GMSE models can be agent‐based and spatially explicit, incorporating a high degree of realism through mechanistic modelling of links and feedbacks among stakeholders and with the ecosystem; additionally, user‐defined sub‐models can also be incorporated as functions into the broader GMSE framework.

We show how GMSE simulates a social‐ecological system using the example of an adaptively managed waterfowl population on an agricultural landscape; simulated waterfowl exploit agricultural land, causing conflict between conservation interests and the interest of food producers maximising their crop yield.

The r package GMSE is open source under GNU Public License; source code and documents are freely available on GitHub.
A Pediatric Emergency Department Intervention to Increase Contraception Initiation Among Adolescents
Authors: Hoehn Erin F. , Hoefgen Holly , Chernick Lauren S. , Dyas Jenna , Krantz Landon , Zhang Nanhua , Reed Jennifer L.
Published: September 2018

Background

The pediatric emergency department (PED) provides care for adolescents at high risk of unintended pregnancy, but little is known regarding the efficacy of PED‐based pregnancy prevention interventions. The objectives of this PED‐based pilot intervention study were to 1) assess the rate of contraception initiation after contraceptive counseling and appointment facilitation in the PED during the study period, 2) identify barriers to successful contraception initiation, and 3) determine adolescent acceptability of the intervention.

Methods

This pilot intervention study included females 14 to 19 years of age at risk for unintended pregnancy. Participants received standardized contraceptive counseling and were offered an appointment with gynecology. Participants were followed via electronic medical record and phone to assess contraception initiation and barriers. Chi‐square tests were used to examine the association between contraception initiation and participant characteristics.

Results

A total of 144 patients were eligible, and 100 were enrolled. In the PED, 68% (68/100) expressed interest in initiating hormonal contraception, with 70% (48/68) of interested participants indicating that long‐acting reversible contraception (LARC) was their preferred method. Twenty‐five percent (25/100) of participants initiated contraception during the study period, with 19 participants starting LARC. Thirty‐nine percent (22/57) of participants who accepted a gynecology appointment attended that appointment. Barriers to follow‐up include transportation and inconvenient follow‐up times. Participants were accepting of the intervention with 93% agreeing that the PED is an appropriate place for contraceptive counseling.

Conclusions

PED contraceptive counseling is acceptable among adolescents and led to successful contraception initiation in 25% of participants. The main barrier to contraception initiation was participant follow‐up with the gynecology appointment.
Price elasticity of illegal versus legal cannabis: a behavioral economic substitutability analysis
Authors: Amlung Michael , Reed Derek D. , Morris Vanessa , Aston Elizabeth R. , Metrik Jane , MacKillop James
Published: September 2018

Background and Aims

The evolving legal status of cannabis world‐wide necessitates evidence‐based regulatory policies to minimize risks associated with cannabis misuse. A prominent concern is the impact legalization may have on the illegal cannabis market, including whether illegal cannabis will serve as a substitute for legal cannabis. Empirical data on this issue are virtually non‐existent. This study used behavioral economics to investigate substitutability of legal and illegal cannabis in legalized catchment areas in the United States.

Design

A substitution‐based marijuana purchase task assessed estimated cannabis consumption from concurrently available legal (a dispensary) and illegal (a dealer) sources. Prices of the two options were reciprocally either held constant ($10/gram) or escalated ($0–$60/gram).

Setting

US states with legalized recreational cannabis.

Participants

Adult cannabis users who were at least 21 years old (n = 724; mean age = 34.13; 52% female; 74% Caucasian) were recruited using online crowdsourcing.

Measurements

Mean consumption values were used in demand curve modeling to generate indices of price sensitivity and elasticity. Differences in demand indices were compared using extra sums‐of‐squares F‐tests.

Findings

Both legal and illegal fixed‐price cannabis options had significant positive cross‐price elasticities (Ps < 0.001), indicating that higher prices motivate substitution irrespective of legality. However, the presence of a legal alternative had a substantially greater effect on consumption and elasticity of illegal cannabis (∆elasticity = 0.0019; F(1,37) = 160, P < 0.0001) than the presence of an illegal alternative on demand for legal cannabis (∆elasticity = 0.0002; F(1,37) = 48, P < 0.0001), indicating asymmetric substitution. Demand for legal cannabis was significantly greater than for illegal cannabis (P < 0.0001).

Conclusions

Cannabis users treat legal cannabis as a superior commodity compared with illegal cannabis and exhibit asymmetric substitutability favoring legal product. Cannabis price policies that include somewhat higher consumer costs for legal cannabis relative to contraband (but not excessively higher costs) would not be expected to incentivize and expand the illegal market.
Alcohol consumption behaviors and neurocognitive dysfunction and emotional distress in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study
Authors: Brinkman Tara M. , Lown E. Anne , Li Chenghong , Tonning Olsson Ingrid , Marchak Jordan Gilleland , Stuber Margaret L. , Vuotto Stefanie , Srivastava Deokumar , Nathan Paul C. , Leisenring Wendy M. , Armstrong Gregory T. , Robison Leslie L. , Krull Kevin R.
Published: September 2018

Aims

To estimate the level of alcohol consumption behaviors in adult survivors of childhood cancer and to test associations between alcohol consumption behaviors and symptoms of neurocognitive impairment and emotional distress.

Design

Retrospective cohort study with longitudinal follow‐up of self‐reported health outcomes.

Setting

Childhood Cancer Survivor Study (CCSS), a 26‐center study of ≥ 5‐year survivors of childhood cancer diagnosed ≤ 21 years of age between 1970 and 1986 in the United States and Canada.

Participants

A total of 4484 adult survivors of childhood cancer [mean (standard deviation) age at evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651 sibling controls who completed surveys reporting on alcohol use, neurocognitive impairment and emotional distress.

Measurements

Survivor report of alcohol use included age at drinking initiation and quantity and frequency of alcohol consumption. Neurocognition was assessed using the CCSS Neurocognitive Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms Inventory–18 and the Posttraumatic Stress Diagnostic Scale.

Findings

After adjustment for childhood cancer treatment exposures, including cranial radiation therapy, drinking initiation prior to 18 years of age was associated with 30% increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95% confidence interval (CI) = 1.1–1.5]. Younger age at drinking initiation was associated with future risk of depression (RR = 1.3; 95% CI = 1.1–1.5), anxiety (RR = 1.6; 95% CI = 1.3–2.1), and somatization (RR = 1.2; 95% CI = 1.1–1.4). Persistent heavy/risky drinking was associated with 80% increased risk of persistent psychological distress (RR = 1.8, 95% CI = 1.4–2.3).

Conclusions

Drinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer.
A typology of prescription drug monitoring programs: a latent transition analysis of the evolution of programs from 1999 to 2016
Authors: Smith Nathan , Martins Silvia S. , Kim June , Rivera‐Aguirre Ariadne , Fink David S. , Castillo‐Carniglia Alvaro , Henry Stephen G. , Mooney Stephen J. , Marshall Brandon D. L. , Davis Corey , Cerdá Magdalena
Published: September 2018

Background and aims

Prescription drug monitoring programs (PDMP), defined as state‐level databases used in the United States that collect prescribing information when controlled substances are dispensed, have varied substantially between states and over time. Little is known about the combinations of PDMP features that, collectively, may produce the greatest impact on prescribing and overdose. We aimed to (1) identify the types of PDMP models that have developed from 1999 to 2016, (2) estimate whether states have transitioned across PDMP models over time and (3) examine whether states have adopted different types of PDMP models in response to the burden of opioid overdose.

Methods

A latent transition analysis of PDMP models based on an adaptation of nine PDMP characteristics classified by prescription opioid policy experts as potentially important determinants of prescribing practices and prescription opioid overdose events.

Results

We divided the time‐period into three intervals (1999–2004, 2005–09, 2010–16), and found three distinct PDMP classes in each interval. The classes in the first and second interval can be characterized as ‘no/weak’, ‘proactive’ and ‘reactive’ types of PDMPs, and in the third interval as ‘weak’, ‘cooperative’ and ‘proactive’. The meaning of these classes changed over time: until 2009, states in the ‘no/weak’ class had no active PDMP, whereas states in the ‘proactive’ class were more likely to proactively provide unsolicited information to PDMP users, provide open access to law enforcement, and require more frequent data reporting than states in the ‘reactive’ class. In 2010–16, the ‘weak’ class resembled the ‘reactive’ class in previous intervals. States in the ‘cooperative’ class in 2010–16 were less likely than states in the ‘proactive’ class to provide unsolicited reports proactively or to provide open access to law enforcement; however, they were more likely than those in the ‘proactive’ class to share PDMP data with other states and to report more federal drug schedules.

Conclusions

Since 1999, US states have tended to transition to more robust classes of prescription drug monitoring programs. Opioid overdose deaths in prior years predicted the state's prescription drug monitoring program class but did not predict transitions between prescription drug monitoring program classes over time.
Life‐history parameters and predation capacity of Macrolophus pygmaeus and Nesidiocoris tenuis (Hemiptera: Miridae) on eggs of Plutella xylostella (Lepidoptera: Plutellidae)
Authors: Ebrahimi Morteza , Mahdian Kamran , De Clercq Patrick
Published: September 2018

The life‐history parameters and predation capacity of Macrolophus pygmaeus Rambur and Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae) fed on eggs of Plutella xylostella (L.) (Lepidoptera: Plutellidae) at 25 °C were investigated in the laboratory and analyzed based on the age‐stage, two‐sex life table. Also, we evaluated the survival and the duration of different stages of these two predators on cabbage plants without prey.

The developmental times of different stages of M. pygmaeus and N. tenuis fed on the eggs of P. xylostella were significantly different. The nymphs of N. tenuis only survived until the fourth instar without prey, and nymphs of M. pygmaeus succeeded in completing the third instar without prey.

The population and predation parameters of the two predators were statistically different. The total consumption rate of the two predators during the oviposition period was higher than the total consumption rate during the post oviposition period and the total preoviposition period.

The highest predation rates for female adults of N. tenuis and M. pygmaeus were on days 33 and 31, respectively.

The nymphs of N. tenuis only survived until the fourth instar without prey, and nymphs of M. pygmaeus succeeded in completing the third instar.
Modulation of trophoblast function by concurrent hyperglycemia and antiphospholipid antibodies is in part TLR4‐dependent
Authors: Leon‐Martinez Daisy , Mulla Melissa J. , Han Christina S. , Chamley Lawrence W. , Abrahams Vikki M.
Published: September 2018

Problem

While diabetes and APS are individually associated with increased risk of poor perinatal outcomes, in particular preeclampsia, recent studies have demonstrated an association between concurrent aPL and diabetes leading to an increased risk of pregnancy morbidity. Hyperglycemia and aPL have independently been shown to alter human trophoblast function by inducing a pro‐inflammatory, anti‐angiogenic, and antimigratory response. However, little is known about the effects of concurrent hyperglycemia and aPL on trophoblast function.

Method of study

A human first‐trimester extravillous trophoblast cell line was exposed to glucose at 5 mmol/L (normoglycemia) or 25 mmol/L (hyperglycemia), all in the presence or absence of low‐dose aPL or control IgG. For some experiments, the TLR4 antagonist, LPS‐RS, was included. Cell culture supernatants were measured for inflammatory IL‐1β and IL‐8, and angiogenic PlGF, sFlt‐1, and sEndoglin by ELISA. Inflammasome‐associated uric acid was measured using a bioassay; caspase‐1 was measured using an activity assay. Trophoblast migration was quantified using a two‐chamber colorimetric assay.

Results

Compared to excess glucose alone, combination excess glucose and low‐dose aPL (a) further augmented trophoblast inflammatory IL‐1β, inflammasome‐associated uric acid and caspase‐1, and pro‐angiogenic PlGF; (b) dampened trophoblast inflammatory IL‐8, anti‐angiogenic sEndoglin, and sFlt‐1; and (c) further reduced trophoblast migration.

Conclusion

Our findings indicate that while concurrent aPL and hyperglycemia are overall detrimental to trophoblast function, the presence of two simultaneous insults triggers some protective effects.
Recovery from the Asian financial crisis: the importance of non‐monetary financial factors
Authors: Xue Wenjun , Taylor Jason E.
Published: September 2018

While it is widely accepted that monetary factors play an integral role in macroeconomic outcomes, Bernanke's () seminal paper highlights the significant role that non‐monetary financial factors played in the downturn and recovery (or lack thereof) from the Great Depression of the 1930s in the USA. This paper explores whether Bernanke's findings can be applied to the recovery from the East Asian financial crisis of 1997–98. We show that non‐monetary financial factors played an important role in how quickly East Asian nations recovered in the years following 1998. Unlike the US experience during the Great Depression, East Asian nations generally implemented positive non‐monetary financial reforms that helped speed recovery. We find that factors correlated with a healthy banking system had a significant, positive effect upon economic growth from 1999 to 2006 and that bank system health was particularly important in those East Asian countries that had traditionally weaker banking systems. Our findings suggest that the reform of financial institutions—such as strengthening financial sector supervision and implementing prudent regulations—should be given more attention when policies are devised to help economies recover from financial crises.
Association between chronic viral hepatitis and metabolic syndrome in southern Taiwan: a large population‐based study
Authors: Kuo Yuan‐Hung , Kee Kwong‐Ming , Wang Jing‐Houng , Hsu Nien‐Tzu , Hsiao Chang‐Chun , Chen Yi , Lu Sheng‐Nan
Published: September 2018

Background

The impact of metabolic syndrome (MetS) on hepatitis is an interesting issue.

Aim

To evaluate the association of MetS and chronic viral hepatitis including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in southern Taiwan.

Methods

From 2004 to 2013, a series of community‐based health screenings for residents aged 40 and older were held in Tainan city. MetS was defined according to the Joint Scientific Statement. Cut‐offs of body‐mass index measures of 24 kg/m2 and 27 kg/m2 were used to stratify lean, overweight and obese subjects.

Results

We enrolled 180 359 participants; the prevalence of MetS was 30.1%, which was significantly associated with advanced age and female sex. There were 18 726 (10.4%) HBV, 13 428 (7.4%) HCV, 1337 (0.7%) HBV plus HCV (B+C) and 146 868 (81.5%) non‐HBV non‐HCV participants (NBNC). Prevalence rates of MetS in subjects with HBV, HCV, B+C and NBNC were 25.2%, 31.5%, 28.9% and 30.7% respectively (P < 0.001). There were 18.8% lean body, 35.4% overweight and 45.8% obese participants among 54 361 MetS subjects. Lean MetS subjects were older, had more diabetes, and had higher metabolic component levels, but lower alanine transaminase and aspartate transaminase‐platelet ratio index levels compared with obese MetS subjects. HCV infection was positively associated with MetS (P < 0.001). However, HBV infection was inversely associated with MetS only among lean subjects (P = 0.002), but not among the general population.

Conclusions

This large population‐based study indicated that HCV infection was positively associated with MetS. However, HBV infection was inversely associated with MetS only among lean subjects.
Retesting the income inequality hypothesis: Pooled time‐series–cross‐section regression with a new statistical case selection method
Authors: Baek Seung‐ho , Kim Ki‐tae
Published: September 2018

The Wilkinson hypothesis, which posits that it is income inequality, rather than economic growth, that determines population health in wealthy societies has been widely debated over decades. This article, with an original case selection process, retests the controversial hypothesis with the time‐series–cross‐section (TSCS) regression model. The main findings are that disposable income inequality is not statistically significantly associated with life expectancy, and its influences on the health of the elderly population are counterintuitively beneficial. Infant mortality rate is the only health indicator that both has the statistically significant association with income inequality and corresponds with the Wilkinson hypothesis. Finally, the relationship between income inequality and population health is not as simple as the hypothesis suggests and found to be dynamic and complex depending on what health indicator is used for the test.
Children's perspectives on neighbourhood barriers and enablers to active school travel: A participatory mapping study
Authors: Wilson Katherine , Coen Stephanie E. , Piaskoski Angela , Gilliland Jason A.
Published: September 2018

Children today are spending more sedentary time indoors than time playing and being active outdoors. The daily journey to and from school represents a valuable opportunity for children to be physically active through active school travel. The majority of research on children's active school travel omits children from the research process even though children interpret their environments in fundamentally different ways than adults. Our research uses innovative participatory mapping and qualitative GIS methods to examine how children's perceptions of their environments influence their school journey experiences. Through our thematic analysis of 25 map‐based focus groups, we identified three main themes characterizing barriers and enablers to active school travel: safety‐related, material, and affective features. By positioning children as experts of their environments in our participatory methodology, our findings provide an important counterpoint to the adultist privilege characterizing the majority of research on children's active school travel. Environmental features that mattered for children's school journeys took on multiple meanings in their eyes, demonstrating that children's perspectives must be engaged to inform interventions to promote active school travel. We thus argue that identifying barriers and enablers to active school travel for children requires engaging children's views.
Immunoglobulin A anti-phospholipid antibodies in Swedish cases of systemic lupus erythematosus: associations with disease phenotypes, vascular events and damage accrual
Authors: Frodlund M , Vikerfors A , Grosso G , Skogh T , Wetterö J , Elvin K , Gunnarsson I , Kastbom A , Dahlström Ö , Rönnelid J , Svenungsson E , Sjöwall C
Published: September 2018

Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-β2-glycoprotein-I (anti-β2GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-β2GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n = 100), primary Sjögren's syndrome (n = 50) and blood donors (n = 507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-β2GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and ≥ 1 aCL/anti-β2GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-β2GPI, 34 (6%) being seronegative regarding IgG/IgM anti-β2GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-β2GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-β2GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR) = 0·21, 95% confidence interval (CI) = 0·06–0·72) and photosensitivity (OR = 0·19, 95% CI = 0·05–0·72). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.
STAT6 and IL-10 are required for the anti-arthritic effects ofSchistosoma mansonivia different mechanisms
Authors: Osada Y , Horie Y , Nakae S , Sudo K , Kanazawa T
Published: September 2018

To investigate possible roles of T helper type 2 (Th2) cytokines in the anti-arthritic effects of a blood fluke, Schistosoma mansoni (Sm), for mouse collagen-induced arthritis (CIA), wild-type (WT), signal transducer and activator of transcription 6 (STAT6) knock-out (KO) and interleukin (IL)-10 KO mice were infected with Sm. Three weeks after infection, the mice were immunized with bovine type II collagen (IIC). Arthritis severity was monitored by scoring, measurement of paw thickness and the presence of ankylosis. Serum anti-IIC IgG levels, splenic cytokine production and cytokine gene expression in the popliteal lymph nodes (PLNs) were measured and compared among WT and gene-KO mice. Consistent with our previous findings, Sm infection reduced the arthritis severity in WT mice. Splenic production of IL-17A and tumor necrosis factor (TNF)-α was reduced by the infection. In contrast, Sm infection markedly exacerbated CIA in STAT6 KO mice. In the KO mice, IL-17A production was increased by the infection. Conversely, Sm infection did not affect the exacerbated arthritis in IL-10 KO mice, although IL-17A production was reduced by the helminth. Our results suggest that signaling via STAT6 (presumably IL-4 and/or IL-13) and IL-10 is required for the suppression of CIA by Sm infection, but through different mechanisms. STAT6 was essential for helminth-induced reduction of IL-17A, whereas regulation of the basal arthritis severity by IL-10 was needed in order for it to be sufficiently suppressed by the helminth.
Fertility induction in hypogonadotropic hypogonadal men
Authors: Prior Matthew , Stewart Jane , McEleny Kevin , Dwyer Andrew A. , Quinton Richard
Published: September 2018

Men with hypogonadotropic hypogonadism (HH) are typically azoospermic, and yet HH is one of the few treatable forms of male infertility. Sperm induction protocols using gonadotrophins aim to replicate the natural endocrine control of spermatogenesis. Previously virilised men with adult‐onset HH and normal testicular volume respond well to monotherapy in which human chorionic gonadotrophin (hCG) acts as a long‐acting LH‐analogue stimulating spermatogenesis. However, this approach is rarely successful for men with congenital HH (CHH) (eg, Kallmann syndrome), for whom combined gonadotrophin therapy (hCG + follicle‐stimulating hormone [FSH]) is an absolute requirement to maximise fertility potential. Key baseline predictors of successful spermatogenesis‐induction include prior spontaneous testicular development (ie, testicular volume [TV] > 4 mL), serum inhibin B (IB) concentration >60 pg/mL and no history of maldescended testes (cryptorchidism).
Cable Joints
Authors: Müller Matthias , Chentanez Nuttapong , Jeschke Stefan , Macklin Miles
Published: September 2018

Robustly and efficiently simulating cables and ropes that are part of a larger system such as cable driven machines, cable cars or tendons in a human or robot is a challenging task. To be able to adapt to the environment, cables are typically modeled as a large number of small segments that are connected via joints. The two main difficulties with this approach are to satisfy the inextensibility constraint and to handle the typically large mass ratio between the small segments and the larger objects they connect.

In this paper we present a new approach which solves these problems in a simple and effective way. Our method is based on the idea to simulate the effect of the cables instead of the cables themselves. To this end we propose a new special type of distance constraint we call cable joint that changes both its attachment points and its rest length dynamically. A cable connecting a series of objects is then modeled as a sequence of cable joints which reduces the complexity of the simulation from the order of the number of segments to just the number of connected objects. This makes simulations both faster and more robust as we will demonstrate on a variety of examples.
Collision‐Aware and Online Compression of Rigid Body Simulations via Integrated Error Minimization
Authors: Jeruzalski Timothy , Kanji John , Jacobson Alec , Levin David I.W.
Published: September 2018

Methods to compress simulation data are invaluable as they facilitate efficient transmission along the visual effects pipeline, fast and efficient replay of simulations for visualization and enable storage of scientific data. However, all current approaches to compressing simulation data require access to the entire dynamic simulation, leading to large memory requirements and additional computational burden. In this paper we perform compression of contact‐dominated, rigid body simulations in an online, error‐bounded fashion. This has the advantage of requiring access to only a narrow window of simulation data at a time while still achieving good agreement with the original simulation. Our approach is simulator agnostic allowing us to compress data from a variety of sources. We demonstrate the efficacy of our algorithm by compressing contact‐dominated rigid body simulations from a number of sources, achieving compression rates of up to 360 times over raw data size.