bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-rRNA processing and its response to temperature stress in maize
Authors: Liu Guoqin , Yan Pengshuai , Du Qingguo , Wang Yafei , Guo Yu , Fu Zhiyuan , Wang Hongqiu , Tang Jihua
Published: October 2019

Ribosome biogenesis is a fundamental process in all eukaryotic cells and is coupled with the processing and maturation of pre-rRNAs. Maize is the primary staple crop across the world. However, little is known about the exact pre-rRNA processing sites and pathways in maize. In this study, we identified the critical endonucleolytic cleavage sites and detected the pre-rRNA intermediates by circular reverse transcription PCR (cRT-PCR) and northern blot, presenting a detailed model of the pre-rRNA processing pathway in maize. We demonstrated that two pathways coexist in maize to promote the processing of 35S pre-rRNA and that the processing of 27SA pre-rRNA could proceed via two different pathways, which were distinguished based on the order of ITS1 removal and ITS2 cleavage. Compared with yeast and mammals, this new 27SA pre-rRNA processing mechanism is unique to maize and other higher plants. Moreover, we discovered that maize could modulate pre-rRNA processing levels in response to chilling and heat stress, as indicated by the significant reduction of P-A3. Our study should facilitate future research on ribosome biogenesis and pre-rRNA processing in maize.
Toward multimodal corpus pragmatics: Rationale, case, and agenda
Authors: Huang Lihe
Published: October 2019

Human interaction is multimodal in nature, and meaning in discourse is created through an interplay of an array of modalities. Inspired by the integration of multimodality and corpus pragmatics, we are concerned with a general multimodal framework that facilitates the exploration on pragmatic questions by using corpus methods. By demonstrating how the study on speech acts in situated discourse is benefited from the multimodal corpus approach, we claim that the scope and methods of pragmatic studies will be enriched and the classic pragmatic theories could be further developed toward multimodal corpus pragmatics. This article, therefore, hopes to inspire further theoretical discussion and case study in this domain.
Mechanical Thrombectomy in Acute Ischemic Stroke Patients Performed Within and Outside Clinical Trials in the United States
Authors: Qureshi Adnan I , Singh Baljinder , Huang Wei , Du Zhiyuan , Lobanova Iryna , Liaqat Jahanzeb , Siddiq Farhan
Published: October 2019

BACKGROUND

A better understanding of differences in outcomes of mechanical thrombectomy performed within and outside clinical trials will assist in optimal implementation of the procedure for acute ischemic stroke patients in general practice.

OBJECTIVE

To identify differences in demographic and clinical characteristics and outcomes related to mechanical thrombectomy in patients treated within clinical trials and those treated outside clinical trials in a large national cohort.

METHODS

 We compared the patient characteristics and associated in-hospital outcomes of mechanical thrombectomy in acute ischemic stroke patients performed within and outside clinical trials using the Nationwide Inpatient Sample from 2013 to 2015. We analyzed in-hospital mortality (primary outcome) and moderate to severe disability (secondary outcome) based on discharge disposition after adjusting for potential confounders.

RESULTS

Of 23 375 patients who underwent mechanical thrombectomy, 430 (1.8%) underwent the procedure as part of a clinical trial. After adjusting for age, gender, and the teaching status of the hospital, patients treated within a clinical trial had lower rates of in-hospital mortality (odds ratio [OR] 0.14; 95% CI .03 to .71; P < .001). Among patients discharged alive, the rate of moderate to severe disability (OR .43; 95% CI .26 to .71; P < .001) was lower among those patients treated within a clinical trial. There was no difference in odds of post-thrombectomy intracerebral or subarachnoid hemorrhage between the two groups.

CONCLUSION

Mechanical thrombectomy performed as part of clinical trials was associated with lower rates of in-hospital mortality and lower rates of moderate to severe disability compared with those performed outside clinical trials.
The double-edged sword of beneficiary consultation
Authors: Carey Bernadette , Duncan Chris
Published: October 2019

Trustees are routinely faced with problems that need solutions, many of which are significant with no clear or easy resolution within reach. Both onshore and offshore, the Public Trustee v Cooper jurisdiction offers a helpful set of court-assisted solutions for a number of different types of issues encountered by trustees. But to what extent should beneficiaries of trusts be able to weave their way into the issue-resolution and decision-making processes, and just how far (and for how long) should the trustee remain engaged in that process? Recent decisions of the Cayman Islands courts offer some helpful guidance in this regard.
Using δ13C and δ18O to analyze loblolly pine (Pinus taeda L.) response to experimental drought and fertilization
Authors: Lin Wen , Domec Jean-Christophe , Ward Eric J , Marshall John , King John S , Laviner Marshall A , Fox Thomas R , West Jason B , Sun Ge , McNulty Steve , Noormets Asko
Published: October 2019

Drought frequency and intensity are projected to increase throughout the southeastern USA, the natural range of loblolly pine (Pinus taeda L.), and are expected to have major ecological and economic implications. We analyzed the carbon and oxygen isotopic compositions in tree ring cellulose of loblolly pine in a factorial drought (~30% throughfall reduction) and fertilization experiment, supplemented with trunk sap flow, allometry and microclimate data. We then simulated leaf temperature and applied a multi-dimensional sensitivity analysis to interpret the changes in the oxygen isotope data. This analysis found that the observed changes in tree ring cellulose could only be accounted for by inferring a change in the isotopic composition of the source water, indicating that the drought treatment increased the uptake of stored moisture from earlier precipitation events. The drought treatment also increased intrinsic water-use efficiency, but had no effect on growth, indicating that photosynthesis remained relatively unaffected despite 19% decrease in canopy conductance. In contrast, fertilization increased growth, but had no effect on the isotopic composition of tree ring cellulose, indicating that the fertilizer gains in biomass were attributable to greater leaf area and not to changes in leaf-level gas exchange. The multi-dimensional sensitivity analysis explored model behavior under different scenarios, highlighting the importance of explicit consideration of leaf temperature in the oxygen isotope discrimination (Δ18Oc) simulation and is expected to expand the inference space of the Δ18Oc models for plant ecophysiological studies.
Mutations in the anti-sigma H factor RshA confer resistance to econazole and clotrimazole in Mycobacterium smegmatis
Authors: Morbidoni Héctor R. , de la Iglesia Agustina I. , Figueroa Virginia , Di Capua Cecilia , Ioerger Thomas R. , Parish Tanya
Published: October 2019

Azole drugs such as econazole, are active on

Mycobacterium tuberculosis

and

Mycobacterium smegmatis

; however, the identification of their target(s) is still pending. It has been reported that mutations in the non-essential system mmpL5-mmpS5 conferred resistance to econazole in

M. tuberculosis

. We herein report that an azole-resistant mutant screen in

M. smegmatis

rendered mutations in rshA, encoding a non-essential anti-sigma H protein.
ARMC9 and TOGARAM1 define a Joubert syndrome-associated protein module that regulates axonemal post-translational modifications and cilium stability
Authors: Latour Brooke L. , Van De Weghe Julie C. , Rusterholz Tamara D. S. , Letteboer Stef J.F. , Gomez Arianna , Shaheen Ranad , Gesemann Matthias , Grout Megan E. , van Reeuwijk Jeroen , Van Beersum Sylvia E.C. , Miller Caitlin V. , Dempsey Jennifer C. , Morsy Heba , Bamshad Michael J. , Nickerson Deborah A. , Neuhauss Stephan C.F. , Boldt Karsten , Ueffing Marius , Alkuraya Fowzan S. , Bachmann-Gagescu Ruxandra , Roepman Ronald , Doherty Dan
Published: October 2019

Joubert syndrome (JBTS) is a recessive neurodevelopmental ciliopathy, characterized by a pathognomonic hindbrain malformation. All known JBTS-genes encode proteins involved in the structure or function of primary cilia, ubiquitous antenna-like organelles essential for cellular signal transduction. Here, we use the recently identified JBTS-associated protein ARMC9 in tandem-affinity purification and yeast two-hybrid screens to identify a novel ciliary module composed of ARMC9-TOGARAM1-CCDC66-CEP104- CSPP1. TOGARAM1-variants cause JBTS and disrupt its interaction with ARMC9. Using a combination of protein interaction analyses and characterization of patient-derived fibroblasts, CRISPR/Cas9-engineered zebrafish and hTERT-RPE1 cells, we demonstrate that dysfunction of ARMC9 or TOGARAM1 results in short cilia with decreased axonemal acetylation and glutamylation, but relatively intact transition zone function. Aberrant serum-induced ciliary resorption and cold-induced depolymerization in both ARMC9 and TOGARAM1 patient cells lines suggest a role for this new JBTS-associated protein complex in ciliary stability.
Evidence for widespread selection in shaping the genomic landscape during speciation ofPopulus
Authors: Wang Jing , Street Nathaniel R. , Park Eung-Jun , Liu Jianquan , Ingvarsson Pär K.
Published: October 2019

Increasing our understanding of how various evolutionary processes drive the genomic landscape of variation is fundamental to a better understanding of the genomic consequences of speciation. However, the genome-wide patterns of within- and between-species variation have not been fully investigated in most forest tree species despite their global ecological and economic importance. Here, we use whole-genome resequencing data from fourPopulusspecies spanning the speciation continuum to reconstruct their demographic histories, investigate patterns of diversity and divergence, infer their genealogical relationships and estimate the extent of ancient introgression across the genome. Our results show substantial variation in these patterns along the genomes although this variation is not randomly distributed but is strongly predicted by the local recombination rates and the density of functional elements. This implies that the interaction between recurrent selection and intrinsic genomic features has dramatically sculpted the genomic landscape over long periods of time. In addition, our findings provide evidence that, apart from background selection, recent positive selection and long-term balancing selection are also crucial components in shaping patterns of genome-wide variation during the speciation process.
The reconstruction and functional mapping of a recurrent microcircuit inDrosophilamushroom body
Authors: Wang Guangxia , Zhou Bangyu , Wang Shengxiong , Yang Kai , Zhao Jianjian , Yang Xing , Li Yiming , Shen Lijun
Published: October 2019

InDrosophila melanogaster, mushroom body and anterior paired lateral (APL) neurons play important roles not only in learning and memory but also in high cognitive behavior, reversal learning. The circuit between APL neurons and Kenyon cells (KCs) in the mushroom body underlies this behavior, including reversal learning, and electron microscopy (EM) methods must be used to reveal this circuit. Here, we reconstructed the connections between mushroom body cells and APL neurons in the vertical lobe of the mushroom body via focused ion beam scanning electron microscopy (FIB-SEM) and sparse genetic horseradish peroxidase (HRP) labeling. We offer the first EM evidence that recurrent network and lateral inhibition connections exist between APL neurons and KCs in the vertical lobe of the mushroom body. This circuit is the neural basis of action selection decision making, associative learning and reversal learning. Additionally, dopamine neurons project to different areas of mushroom bodies and, together with extrinsic neurons and KC axons, form a compartmental structure of mushroom body axons, thereby restricting the KC-mushroom body output neuron (MBON) response to local compartments. Whether APL neurons also respond locally is uncertain. We found that APL neurons exhibited input and output synapses that were intermixed and arranged on enlarged and thin sections, respectively, resembling a string of beads. Different KCs were found to project to APL neurons nonrepetitively, forming a local circuit structure. Furthermore, using a single neurite calcium imaging method, we identified local calcium domains on this circuit, suggestive of individual electrical compartments. The electrically recorded APL neurons were nonspike neurons that selectively responded to odor in both the lobes and calyx. Thus, the localized APL neuron responses coordinate with mushroom body–dopamine-MBON compartmental function.
In silico investigation of Y220C mutant p53 for lead design
Authors: Chowdhury Mayank Roy , Tiwari Anamika , Dubey G.P.
Published: October 2019

p53 protein coded by the Tp53 gene is considered as one of the most intensively researched protein and mainly due to its role as a tumor suppressor, it acts as a tumor suppressor by carrying out two biologically complex processes namely Cell cycle arrest and apoptosis, In the oncogenic Y220C mutant p53, tyrosine is replaced by cysteine at 220th residue of the DNA binding Domain which causes the formation of a surface crevice, this specific mutation is responsible for approx. 100,000 cancer cases per year due to the destabilization and denaturation of the protein, as a result, the protein degrades at room temperature. In this work we carry out intensive Molecular Dynamic Simulations and Molecular Docking Studies to understand the structural dynamics of wild type p53 and changes the occurs in the mutant protein and also try to design lead against the druggable crevice and at the end of our study we used fragment-based optimization to come up with lead molecules which can act as scaffold for further drug development process
DNA Methylation Signature on Phosphatidylethanol, not Self-Reported Alcohol Consumption, Predicts Hazardous Alcohol Consumption in Two Distinct Populations
Authors: Liang Xiaoyu , Justice Amy C. , So-Armah Kaku , Krystal John H. , Sinha Rajita , Xu Ke
Published: October 2019

The process of diagnosing hazardous alcohol drinking (HAD) is based on self-reported data and is thereby vulnerable to bias. There has been an interest in developing epigenetic biomarkers for HAD that might complement clinical assessment. Because alcohol consumption has been previously linked to DNA methylation (DNAm), here, we aimed to select DNAm signatures in blood to predict HAD from two demographically and clinically distinct populations (Ntotal=1,549). We first separately conducted an epigenome-wide association study (EWAS) for phosphatidylethanol (PEth), an objective measure of alcohol consumption, and for self-reported alcohol consumption in Cohort 1. We identified 102 PEth-associated CpGs, including 32 CpGs previously associated with alcohol consumption or alcohol use disorders. In contrast, no CpG reached epigenome-wide significance on self-reported alcohol consumption. Using a machine learning approach, two subsets of CpGs from EWAS on PEth and on self-reported alcohol consumption from Cohort 1 were separately tested for the prediction of HAD in Cohort 2. We found that a subset of 130 CpGs selected from the EWAS on PEth showed an excellent prediction of HAD with area under the ROC curve (AUC) of 91.31% in training set and 70.65% in validation set of Cohort 2. However, CpGs preselected from the EWAS on self-reported alcohol consumption showed a poor prediction of HAD with AUC 75.18% in the training set and 57.60% in the validation set. Our results demonstrate that an objective measure for alcohol consumption is a more informative phenotype than self-reported data for revealing epigenetic mechanism. The PEth-associated DNAm signature in blood is a robust biomarker for alcohol consumption.
Evaluating physicians’ serendipitous knowledge discovery in online discovery systems
Authors: Hopkins Mark E. , Zavalina Oksana L.
Published: October 2019

Purpose

A new approach to investigate serendipitous knowledge discovery (SKD) of health information is developed and tested to evaluate the information flow-serendipitous knowledge discovery (IF-SKD) model. The purpose of this paper is to determine the degree to which IF-SKD reflects physicians’ information behaviour in a clinical setting and explore how the information system, Spark, designed to support physicians’ SKD, meets its goals.

Design/methodology/approach

The proposed pre-experimental study design employs an adapted version of the McCay-Peet’s (2013) and McCay-Peet et al.’s (2015) serendipitous digital environment (SDE) questionnaire research tool to address the complexity associated with defining the way in which SKD is understood and applied in system design. To test the IF-SKD model, the new data analysis approach combining confirmatory factor analysis, data imputation and Monte Carlo simulations was developed.

Findings

The piloting of the proposed novel analysis approach demonstrated that small sample information behaviour survey data can be meaningfully examined using a confirmatory factor analysis technique.

Research limitations/implications

This method allows to improve the reliability in measuring SKD and the generalisability of findings.

Originality/value

This paper makes an original contribution to developing and refining methods and tools of research into information-system-supported serendipitous discovery of information by health providers.
Administrative staff self-reported long-term conditions
Authors: Wright Kathy Lee , Verney Karen , Brennan Daryl , Lindsay David , Lindsay Daniel , Smyth Wendy
Published: October 2019

Purpose

The purpose of this paper is to investigate the long-term conditions affecting the administration workforce of a regional Australian health service, and their self-management of these conditions.

Design/methodology/approach

A cross-sectional survey design was used. The sample consisted of all administration staff members employed in 2018 across a large regional health service in Northern Australia.

Findings

Of the 328 respondents, 167 (51 per cent) reported having at least one long-term condition. Of these, 136 (81.4 per cent) indicated a single main condition for which management strategies were used. Musculoskeletal conditions were the most commonly nominated category (59.6 per cent), followed by mental health (10.3 per cent). Respondents with musculoskeletal conditions were statistically more likely to have a co-existing mental health long-term condition, χ2(1) = 95.64, p<0.001. There was also a statistically significant association between respondents reporting a mental health condition and being overweight, χ2(1) = 54.27, p< 0.05.

Research limitations/implications

The response rate of 35 per cent, whilst relatively low, is a slight increase on similar surveys within this organisation. The reliability of the self-report data, presence of study bias and a weakening of the study’s external validity is acknowledged.

Practical implications

Targeted workplace intervention strategies, such as holistic wellness programs, should complement personal approaches, promote an ergonomic environment and create opportunities for increased dialogue between employees and their line managers, particularly regarding the complex interplay between long-term physical and mental health.

Originality/value

This is the first study of self-reported long-term conditions among administration staff within a health service, and augments findings from previous studies involving health professional groups in the same organisation.
Moisture absorption in thick composite plates: modelling and experiments
Authors: Canale Giacomo , Kinawy Moustafa , Sathujoda Prabhakar , Maligno Angelo , Citarella Roberto Guglielmo
Published: October 2019

Purpose

When a thick structure is, on the contrary, subjected to moisture absorption, a fairly long time may be needed to reach full saturation. It is, therefore, important to understand and predict the areas of complex composite structures that are more prone to saturation. The material knock-down factors (proportional to the moisture content) may be applied only to these zones, in order to obtain a less pessimistic structural response prediction. The purpose of this paper is to investigate an FE diffusion model that was used to validate the absorption testing results of thick carbon epoxy laminates.

Design/methodology/approach

The experimental results were validated by using a diffusion model in Abaqus FE code.

Findings

The absorption results of three 15 mm thick carbon epoxy laminates are presented and reproduced via a mass diffusion model. The laminates were conditioned at 70°C and 85 per cent relative humidity in a moisture chamber. Areas more prone to saturation have been predicted by the FE model and the moisture content in the non-saturated areas has been calculated.

Practical implications

The practical implications of the absorption model are discussed on an example of an aero-engine fan blade-like structure.

Originality/value

Validation of thick panels’ absorption data is an important point of novelty of this paper, given the lack of experimental and modelling validation in the open literature.
Discrimination in the United States: Experiences of lesbian, gay, bisexual, transgender, and queer Americans
Authors: Casey Logan S. , Reisner Sari L. , Findling Mary G. , Blendon Robert J. , Benson John M. , Sayde Justin M. , Miller Carolyn
Published: October 2019

Objective

To examine reported experiences of discrimination against lesbian, gay, bisexual, transgender, and queer (LGBTQ) adults in the United States, which broadly contribute to poor health outcomes.

Data Source and Study Design

Data came from a national, probability‐based telephone survey of US adults, including 489 LGBTQ adults (282 non‐Hispanic whites and 201 racial/ethnic minorities), conducted January‐April 2017.

Methods

We calculated the percentages of LGBTQ adults reporting experiences of discrimination in health care and several other domains related to their sexual orientation and, for transgender adults, gender identity. We report these results overall, by race/ethnicity, and among transgender adults only. We used multivariable models to estimate adjusted odds of discrimination between racial/ethnic minority and white LGBTQ respondents.

Principal Findings

Experiences of interpersonal discrimination were common for LGBTQ adults, including slurs (57 percent), microaggressions (53 percent), sexual harassment (51 percent), violence (51 percent), and harassment regarding bathroom use (34 percent). More than one in six LGBTQ adults also reported avoiding health care due to anticipated discrimination (18 percent), including 22 percent of transgender adults, while 16 percent of LGBTQ adults reported discrimination in health care encounters. LGBTQ racial/ethnic minorities had statistically significantly higher odds than whites in reporting discrimination based on their LGBTQ identity when applying for jobs, when trying to vote or participate in politics, and interacting with the legal system

Conclusions

Discrimination is widely experienced by LGBTQ adults across health care and other domains, especially among racial/ethnic minorities. Policy and programmatic efforts are needed to reduce these negative experiences and their health impact on sexual and/or gender minority adults, particularly those who experience compounded forms of discrimination.
Association of adipokines with rheumatic disease activity indexes and periodontal disease in patients with early rheumatoid arthritis and their first‐degree relatives
Authors: Chaparro‐Sanabria Jeimy A. , Bautista‐Molano Wilson , Bello‐Gualtero Juan M. , Chila‐Moreno Lorena , Castillo Diana M. , Valle‐Oñate Rafael , Chalem Phillipe , Romero‐Sánchez Consuelo
Published: October 2019

Objective

To evaluate the adipokine levels in early rheumatoid arthritis (eRA) and first‐degree relatives (FDR) of patients with RA and establish their association with rheumatic disease activity and periodontal variables.

Method

A cross‐sectional study with eRA patients, FDR and a healthy population. Adipokine levels, clinical, joint radiological indexes and periodontal variables were evaluated. A descriptive, bivariate analysis was performed based on the adipokine levels by χ2, Fisher's test and Mann–Whitney U test. A logistic regression was made for associations.

Results

High leptin levels were associated with the diagnosis of eRA (odds ratio [OR] = 2.79; 95% CI 1.54‐5.07). Early rheumatoid arthritis with high adiponectin levels was less likely to have Multidimensional Health Assessment Questionnaire score >3, body mass index (BMI) >25 and Routine Assessment of Patient Index Data 3 score >12 (OR = 0.16; 95% CI 0.03‐0.72). Early rheumatoid arthritis was more likely to present high leptin and interleukin (IL)6 levels with low adiponectin simultaneously (OR = 5.03; 95% CI 1.05‐24.0). High leptin levels were associated with the FDR adjusted for IgG2 Porphyromonas gingivalis, swollen joints, P gingivalis and low IL6 (OR = 2.57; 95% CI 1.14‐5.95).

Conclusion

High adipokine levels in eRA may modulate the disease activity. Having more than 1 adipokine at high serum levels is associated with increased disability, disease activity and BMI, indicating that RA is controlled by adiponectin levels in the early stages of the disease. High leptin levels, presence of P gingivalis and swollen joints may be the factors associated with the development of RA in FDR.
Diffusion of effects of the ASSIST school‐based smoking prevention intervention to non‐participating family members: a secondary analysis of a randomized controlled trial
Authors: White James , Holliday Jo , Daniel Rhian , Campbell Rona , Moore Laurence
Published: October 2019

Aims

To investigate whether effects of the ASSIST (A Stop Smoking In Schools Trial) school‐based smoking prevention intervention diffused from students to the people they lived with.

Design

Secondary analysis of a cluster‐randomized control trial (cRCT).

Setting

England and Wales.

Participants

A total of 10 730 students aged 12–13 years in 59 schools assigned using stratified block randomization to the control (29 schools, 5372 students) or intervention (30 schools, 5358 students) condition.

Intervention and comparator

The ASSIST intervention involves 2 days of off‐site training of influential students to encourage their peers not to smoke during a 10‐week period. The control group continued with their usual education.

Measurements

The outcomes were the proportion of students who self‐reported living with a smoker and the smoking status of each resident family member/caregiver. Follow‐up assessments were immediately after the intervention and at 1 and 2 years post‐intervention.

Findings

The odds ratio (OR) for living with a smoker in the intervention compared with the control groups was 0.86 [95% confidence interval (CI) = 0.72, 1.03] immediately after the intervention, OR = 0.84 (95% CI = 0.72, 0.97) at a 1‐year follow‐up and OR = 0.86 (95% CI = 0.75, 0.99) at 2‐year follow‐up. In a three‐tier multi‐level model with data from all three follow‐ups, student‐reported smoking by fathers (OR = 0.90, 95% CI = 0.80, 1.00), brothers (OR = 0.78, 95% CI = 0.67, 0.92) and sisters (OR = 0.80, 95% CI = 0.69, 0.92) was lower in the intervention compared with control group. Subgroup analyses by baseline smoking status suggested that these effects were more consistent with prevention of uptake than prompting cessation.

Conclusions

A Stop Smoking In Schools Trial (ASSIST) school‐based smoking prevention intervention may have reduced the prevalence of smoking in people who lived with ASSIST‐trained students. This indirect transmission is consistent with the predictions of diffusion of innovations theory which underpins the design of ASSIST.
Substance use disorders and risk for treatment resistant depression: a population‐based, nested case‐control study
Authors: Brenner Philip , Brandt Lena , Li Gang , DiBernardo Allitia , Bodén Robert , Reutfors Johan
Published: October 2019

Background and aims

Treatment‐resistant depression (TRD), defined as inadequate treatment response after at least two adequate treatment trials, is common among patients initiating antidepressant treatment. Current or previous substance use disorders (SUD) are common among patients with depression and often lead to worse treatment outcomes. However, in clinical studies, SUD have not been found to increase the risk for TRD. The aim of this study was to investigate the association between SUD and TRD.

Design

Nested case–control study.

Setting

Nation‐wide governmental health‐care registers in Sweden.

Cases and controls

Data on prescribed drugs and diagnoses from specialized health care were used to establish a prospectively followed cohort of antidepressant initiators with depression (n = 121 669) from 2006 to 2014. Of these, 15 631 patients (13%) were defined as TRD cases, with at least three treatment trials within a single depressive episode. Each case with TRD was matched on socio‐demographic data with five controls with depression.

Measurements

Crude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) estimated the association between TRD and SUD diagnosis and/or treatment in five different time intervals until the time for fulfillment of TRD definition for the case. The analysis was adjusted for clinical and socio‐demographic covariates.

Findings

Having any SUD during, or ≤ 180 days before start of, antidepressant treatment was associated with almost double the risk for TRD [≤ 180 days before: adjusted OR (aOR) = 1.86, CI = 1.70–2.05]. Increased risks for TRD were found ≤ 180 days before treatment start for the subcategories of sedative use (aOR = 2.37; 1.88–2.99), opioids (aOR = 2.02; 1.48–2.75), alcohol (aOR = 1.77; CI = 1.59–1.98) and combined substance use (aOR = 2.31; 1.87–2.99).

Conclusions

Recent or current substance use disorders is positively associated with treatment resistance among patients initiating treatment for depression.
New psychoactive substances (NPS) in the Netherlands: occurrence in forensic drug samples, consumer drug samples and poisons center exposures between 2013 and 2017
Authors: Hondebrink Laura , Nugteren‐van Lonkhuyzen Johanna J. , Hunault Claudine C. , van den Berg Jorrit , van der Gouwe Daan , van Riel Antoinette J. H. P.
Published: October 2019

Background and Aims

Although European‐wide data on the new psychoactive substances (NPS) drug market are available, country‐specific data are limited. We studied recent NPS trend data relative to all recreational drugs on the Dutch drug market.

Design

National observational study.

Setting

The Netherlands.

Data sources

Three national indicators were used between 2013 and 2017: (1) forensic drug samples offered to the Netherlands Forensic Institute (NFI); (2) drug samples submitted by consumers to the Drugs Information and Monitoring System (DIMS); and (3) exposures in which the Dutch Poisons Information Center (DPIC) was consulted.

Measurements

Overall NPS incidence rate was the primary outcome. Numbers and specific categories of NPS were also studied. Changes in NPS incidence rates over time were analyzed using Poisson regression analyses [year effect expressed as incidence rate ratios (IRR)].

Findings

From 2013 to 2017, NPS were involved in 1892 forensic samples, 6316 consumer samples and 481 poisons center exposures. In 2013, NPS incidence rates were 2.5, 7 and 4% versus 3, 11 and 11% in 2017, respectively, in the NFI, DIMS and DPIC samples/exposures. NPS incidence rates increased significantly in consumer samples between 2013 and 2016 [IRR = 1.23; 95% confidence interval (CI) = 1.18, 1.29] and in poisons center exposures between 2013 and 2017 (IRR = 1.19; 95% CI = 1.06, 1.35), while the trend in forensic samples appeared more stable. Phenethylamines were the largest class and were detected in 58, 80 and 63% of NFI, DIMS and DPIC samples/exposures, respectively. Detected phenethylamines mainly involved 4‐fluoroamphetamine and 2C‐x derivatives. The second largest class were cathinones, which were detected in 21, 11 and 16% of NFI, DIMS and DPIC samples/exposures, respectively.

Conclusions

Analysis of forensic drug samples, consumer drug samples and exposures reported to poison centers from 2013 to 2017 shows the constant presence of new psychoactive substances on the Dutch drug market and its use by the Dutch population. The two largest classes present in the Netherlands were phenethylamines and cathinones.
Acute post‐streptococcal glomerulonephritis in Central Australia
Authors: Dowler James , Wilson Angela
Published: October 2019

Objective

To determine the incidence, clinical presentation and progress of acute post‐streptococcal glomerulonephritis in Central Australia.

Design

Retrospective observational analysis.

Setting

Paediatric inpatient admission at Alice Springs Hospital.

Participants

Patients admitted to Alice Springs Hospital under 14 years of age meeting diagnostic criteria for acute post‐streptococcal glomerulonephritis between January 2010 and December 2014.

Main Outcome Measures

Incidence of acute post‐streptococcal glomerulonephritis in central Australia. Biochemical abnormalities associated with acute post‐streptococcal glomerulonephritis. Co‐occuring conditions.

Results

Sixty‐nine out of the 174 cases reviewed were identified as having either acute post‐streptococcal glomerulonephritis (63) or probable acute post‐streptococcal glomerulonephritis (6). We calculate the incidence of APSGN admission to be higher than previously reported and the highest reported incidence globally in children. Clinical evidence of skin infection was frequently documented. Co‐occurring infections were common, including scabies/head lice, urinary tract infection and pneumonia. Fifty‐three patients showed biochemical evidence of acute kidney injury.

Conclusions

Aboriginal children in Central Australia have the highest incidence of acute post‐streptococcal glomerulonephritis reported worldwide. Urgent action is required to improve housing and reduce overcrowding in Central Australian towns and communities to reduce the burden of disease of skin infection and Group A Streptococcus related diseases. Without effective change in living conditions, it is unlikely that there will be a significant change in the morbidity related to these conditions.
Investigating the clinical factors and comedications associated with circulating levels of atorvastatin and its major metabolites in secondary prevention
Authors: Turner Richard M. , Fontana Vanessa , FitzGerald Richard , Morris Andrew P. , Pirmohamed Munir
Published: October 2019

Aims

The lipid‐lowering drug, atorvastatin (ATV), is 1 of the most commonly prescribed medications worldwide. The aim of this study was to comprehensively investigate and characterise the clinical factors and comedications associated with circulating levels of ATV and its metabolites in secondary prevention clinical practice.

Methods

The plasma concentrations of ATV, 2‐hydroxy (2‐OH) ATV, ATV lactone (ATV L) and 2‐OH ATV L were determined in patients 1 month after hospitalisation for a non‐ST elevation acute coronary syndrome. Factors were identified using all subsets multivariable regression and model averaging with the Bayesian information criterion. Exploratory genotype‐stratified analyses were conducted using ABCG2 rs2231142 (Q141K) and CYP2C19 metaboliser status to further investigate novel associations.

Results

A total of 571 patients were included; 534 and 37 were taking ATV 80 mg and 40 mg daily, respectively. Clinical factors associated with ATV and/or its metabolite levels included age, sex, body mass index and CYP3A inhibiting comedications. Smoking was newly associated with increased ATV lactonisation and reduced hydroxylation. Proton pump inhibitors (PPIs) and loop diuretics were newly associated with modestly increased levels of ATV (14% and 38%, respectively) and its metabolites. An interaction between PPIs and CYP2C19 metaboliser status on exposure to specific ATV analytes (e.g. interaction P = .0071 for 2‐OH ATV L) was observed. Overall model R2 values were 0.14–0.24.ConclusionMultiple factors were associated with circulating ATV and metabolite levels, including novel associations with smoking and drug–drug(–gene) interactions involving PPIs and loop diuretics. Further investigations are needed to identify additional factors that influence ATV exposure.
Adverse events following cannabis for medical use in Tuscany: An analysis of the Italian Phytovigilance database
Authors: Crescioli Giada , Lombardi Niccolò , Bettiol Alessandra , Menniti‐Ippolito Francesca , Da Cas Roberto , Parrilli Maria , Del Lungo Martina , Gallo Eugenia , Mugelli Alessandro , Maggini Valentina , Firenzuoli Fabio , Vannacci Alfredo
Published: October 2019

Aims

Despite a significant increase in using cannabis for medical purposes, current evidence on its safety in real‐world clinical practice is still poorly characterised. By a case‐by‐case analysis of spontaneous reports of suspected adverse events (AEs) collected in Tuscany within the Italian Phytovigilance database, the aim of the present study was to describe AEs occurred in patients exposed to medical cannabis.

Methods

We evaluated all reports of cannabis‐related suspected AEs collected within the Phytovigilance database up to December 2018. Information regarding cannabis therapy, patient's demographic and clinical characteristics, concomitant medications, AE description according to the Medical Dictionary for Regulatory Activities (MedDRA) classification, AE seriousness and AE outcome, were collected. The causality assessment was performed following World Health Organisation–Uppsala Monitoring Centre criteria.

Results

Fifty‐three cannabis‐related AE reports were analysed. The majority of patients were females (77.3%), with a mean age of 61.9 years. Thirty‐nine (73.6%) cases were defined as nonserious and the majority of them (86.9%) showed a complete resolution or improvement. Forty‐six (86.8%) cases were judged as probably related to cannabis consumption. The most frequently reported system organ class was psychiatric and nervous system disorders, and a potential drug–drug interaction was present in 16 cases.

Conclusion

Cannabis was generally well tolerated and the majority of AEs were mild and transient. Our analysis highlighted important safety issues for clinical practice, in particular the need for an accurate prescription monitoring during the titration phase, particularly in the presence of concomitant medications.
From Big to Small Cities: A Qualitative Analysis of the Causes and Outcomes of Post–Recession Municipal Bankruptcies
Authors: Davidson Mark
Published: October 2019

Two cities loom large in the history of American urban restructuring. New York City's 1975 technical bankruptcy and Detroit's 2013 Chapter 9 bankruptcy have played an oversized role in urban theory. This is currently reflected in competing theories of post–recession urban restructuring. “Austerity urbanism” uses Detroit as an exemplar, whereas “pragmatic municipalism” adopts the converse position arguing post–recession reform is defined by local context. This paper draws on the small cities literature to generate a different account of recent municipal bankruptcies and their broader impacts. It uses qualitative methods to survey the causes and outcomes of all eight post–recession Chapter 9 bankruptcies. The research recognizes the potential nationwide significance of these extreme events but avoids focusing on big city examples. The paper's findings suggest small and medium sized cities play a significant role in shaping recession–related restructuring.
Simulation, synthesis, characterisation and dyeing properties of a fluorescent hemicyanine dye
Authors: Tang Songsong , Qin Chuanxiang , Li Hui , Chen Guoqiang
Published: October 2019

In this study, a hemicyanine dye, trans‐4‐(4‐(diethylamino)styryl)‐1‐ethylpyridinium bromide (DYE‐BD), was synthesised and simulated. The maximum absorption wavelength of DYE‐BD was calculated with the same basis set by using the Gaussian 09 software based on different methods, while time‐dependent density functional theory was applied to simulate the maximum emission wavelength of the designed dye. The changes in enthalpy and Gibbs free energy were simulated at the b3lyp/6‐31G(d) level, and energy changes in the luminescence process were assessed using mathematical methods. Furthermore, DYE‐BD was used to colour acrylic fabric following the typical dyeing procedure for cationic dyes. The photostability of the synthesised dye was analysed using quantum theory and mathematical methods. The synthesised dye, analysed using the Ecological Structure Activity Relationships class program, had no toxicity to aquatic life, while the acrylic fabrics dyed with DYE‐BD met the fluorescent orange requirements for background and combined performance materials according to the EN ISO 20471:2013 standard.
South African service users’ perceptions of patient‐reported outcome and experience measures for adolescent substance use treatment: A qualitative study
Authors: Myers Bronwyn , Johnson Kim , Lucas Warren , Govender Rajen , Manderscheid Ron , Williams Petal Petersen , Koch J. Randy
Published: October 2019

Introduction and Aims

Patient‐reported outcome measures (PROM) and experience measures (PREM) for substance use disorder (SUD) treatment exist for adults but have unknown relevance for adolescents. This study aimed to explore adolescents' perceptions of effective SUD treatment and possible barriers to completing PROMs and PREMs to guide efforts to adapt the South African Addiction Treatment Services Assessment (SAATSA) for adolescents.

Design and Methods

Five focus groups were conducted with 38 adolescent service users recruited from residential and outpatient SUD treatment facilities in South Africa. Group discussions explored perceptions of treatment components necessary for desired SUD treatment outcomes, treatment experiences that support engagement in care, and perceptions of PROM and PREM completion.

Results

Participants viewed treatment elements that enhance motivation for change, coping and emotional regulation; provide recreational alternatives to substance use; and improve family relationships and home environments as critical to positive treatment outcomes. They reflected that provider characteristics and developmentally and culturally appropriate services facilitated engagement in treatment. PROM and PREM completion seemed acceptable, with participants suggesting ways to enhance their appeal.

Discussion and Conclusion

Findings confirm that adult‐oriented PROMs and PREMs require adaptation for adolescents. Service user inputs identified ways to expand the content of the SAATSA to better reflect adolescents' treatment priorities. These inputs have also guided changes to item formulation and administration procedures to enhance the SAATSA's acceptability for adolescents. Ensuring the SAATSA addresses treatment outcomes and experiences that matter to adolescents is vital for generating information to guide improvements to adolescent SUD services.
Hepatocellular carcinoma with inferior vena cava and right atrial tumor thrombus: A case report
Authors: Chen Meihua , Huang Xuning , Yang Qianyu
Published: October 2019

This is a case report of a 45‐year‐old patient admitted with the symptom of bilateral leg swelling. Ultrasonography revealed a hyperechoic mass in the right lobe of the liver, which invaded the right hepatic vein (RHV) and extended into the inferior vena cava (IVC) and right atrium (RA). Based on the high alpha‐fetoprotein (AFP) level and the ultrasonography findings, the patient was diagnosed as having hepatocellular carcinoma (HCC) with a RHV, IVC, and RA tumor thrombus and secondary Budd–Chiari syndrome (BCS). HCC with a tumor thrombus extending into the IVC and RA has rarely been observed, and as a cause of secondary BCS, this type of HCC has been even more rarely reported.
The European Union and the Background of the Global Compacts
Authors: Martín Díaz Emma , Aris Escarcena Juan Pablo
Published: October 2019

This article explores the influence of the European Union in shaping and promoting the discourse, theoretical bases and political practices that make up the Global Compact on Refugees and the Global Compact on Safe, Orderly, and Regular Migration. It analyses the experiences and dynamics of European Union policies in its most recent history, and explores its operational, discursive and practical dimensions, focusing on the example of the EU's partnership with Turkey.
Effectiveness of epoprostenol in the management of pulmonary arterial hypertension: findings of an Australian retrospective chart review
Authors: Feenstra John , Hopkins Peter , Trotter Michael , O'Brien Kathy
Published: October 2019

Background

Pulmonary arterial hypertension (PAH) is a progressively fatal disease. Parenteral prostanoids, including intravenous (IV) epoprostenol, are the most effective therapies for PAH. As epoprostenol requires continuous infusion, therapy is challenging and use is managed by specialist units.

Aims

To describe the clinical outcomes for the use of IV epoprostenol in an Australian pulmonary vascular disease unit and identify opportunities to improve its use.

Method

We conducted a retrospective chart review of all adult patients who received IV epoprostenol for PAH at Prince Charles Hospital. Data were collected at baseline, initiation of epoprostenol and quarterly to the end of the audit period or the discontinuation of epoprostenol. Descriptive statistics were performed and comparisons made to epoprostenol initiation. Kaplan–Meier curves were used to estimate survival outcomes.

Results

Thirty‐nine patients received epoprostenol therapy. Most (87.2%) were female, had connective tissue disease (46.2%) or idiopathic PAH (35.9%) and had a World Health Organization functional Class of III or IV at initiation. The mean duration of epoprostenol therapy was 2.9 years. Intravenous epoprostenol was associated with favourable outcomes; 1, 3 and 5‐year survival rates since initiation of 90.0, 75.8 and 68.2%; robust improvements in functional class; and improvements in 6‐min walking distance of 160.4 m at 3 years; 94.9% patients experienced at least one drug‐related adverse event and line complications were common.

Conclusion

Epoprostenol therapy was associated with impressive survival rates and durable improvements in functional outcomes. Epoprostenol therapy is challenging; however, it is manageable by the majority of patients with most experiencing positive, sustainable outcomes.