bluuebunny/crossref_metadata_2025 huggingface dataset:
The Correlation between MicroRNA-199a and White Adipose Tissue in C57/BL6J Mice with High-Fat Diet
Authors: Liu Dan , Wang Xia , Lin Xinying , Zhang Baihui , Wang Shue , Bao Wei
Published: July 2017

Understanding is emerging about microRNAs as mediators in the regulation of white adipose tissue (WAT) and obesity. The expression level of miR-199a in mice was investigated to test our hypothesis: miR-199a might be related to fat accumulation and try to find its target mRNA, which perhaps could propose strategies with a therapeutic potential affecting the fat storage. C57/BL6J mice were randomly assigned to either a control group or an obesity model group (n=10 in both groups). Control mice were fed a normal diet (fat: 10 kcal %)ad libitumfor 12 weeks, and model mice were fed a high-fat diet (fat: 30 kcal %)ad libitumfor 12 weeks to induce obesity. At the end of the experiment, body fat mass and the free fatty acids (FFAs) and triglycerides (TGs) in WAT were tested. Fat cell size was measured by hematoxylin-eosin (H&E) staining method. The fat mass of the model group was higher than that of the control group (P<0.05). In addition, the concentrations of the FFAs and TGs were higher (P<0.05) and the adipocyte count was lower (P<0.05) in the model group. We tested the expression levels of miR-199a and key adipogenic transcription factors, including peroxisome proliferator activated receptor gamma2 (PPARγ2), CCAAT/enhancer binding proteins alpha (C/EBPα), adipocyte fatty acid-binding protein (aP2), and sterol regulatory element binding protein-1c (SREBP-1c). Up-regulated expression of miR-199a was observed in model group. Increased levels of miR-199a was accompanied by high expression levels of SREBP-1c. We found that the 3’-UTR of SREBP-1c mRNA has a predicted binding site for miR-199a. Based on the current discoveries, we suggest that miR-199a may exert its action by binding to its target mRNA and cooperate with SREBP-1c to induce obesity. Therefore, if the predicted binding site is confirmed by further research, miR-199a may have therapeutic potential for obesity.

Abbreviations

WAT, white adipose tissue; PPARγ2, peroxisome proliferator, activated receptor γ2; C/EBP αCCAAT/enhancer binding proteins α; aP2, adipocyte fatty acid-binding protein; SREBP-1c, sterol regulatory element binding protein-1c; HFD, high-fat diet.
Operating regimes of covalent modification cycles at high enzyme concentrations
Authors: Straube Ronny
Published: July 2017

The Goldbeter-Koshland model has been a paradigm for ultrasensitivity in biological networks for more than 30 years. Despite its simplicity the validity of this model is restricted to conditions when the substrate is in excess over the converter enzymes − a condition that is easy to satisfyin vitro, but which is rarely satisfiedin vivo. Here, we analyze the Goldbeter-Koshland model by means of the total quasi-steady state approximation which yields a comprehensive classification of the steady state operating regimes under conditions when the enzyme concentrations are comparable to or larger than that of the substrate. Where possible we derive simple expressions characterizing the input-output behavior of the system. Our analysis suggests that enhanced sensitivity occurs if the concentration of at least one of the converter enzymes is smaller (but not necessarily much smaller) than that of the substrate and if that enzyme is saturated. Conversely, if both enzymes are saturated and at least one of the enzyme concentrations exceeds that of the substrate the system exhibits concentration robustness with respect to changes in that enzyme concentration. Also, depending on the enzyme’s saturation degrees and the ratio between their maximal reaction rates the total fraction of phosphorylated substrate may increase, decrease or change nonmonotonically as a function of the total substrate concentration. The latter finding may aid the interpretation of experiments involving genetic manipulations of enzyme and substrate abundances.
Capturing the diversity of biological tuning curves using generative adversarial networks
Authors: Arakaki Takafumi , Barello G. , Ahmadian Yashar
Published: July 2017

Tuning curves characterizing the response selectivities of biological neurons often exhibit large degrees of irregularity and diversity across neurons. Theoretical network models that feature heterogeneous cell populations or random connectivity also give rise to diverse tuning curves. However, a general framework for fitting such models to experimentally measured tuning curves is lacking. We address this problem by proposing to view mechanistic network models as generative models whose parameters can be optimized to fit the distribution of experimentally measured tuning curves. A major obstacle for fitting such models is that their likelihood function is not explicitly available or is highly intractable to compute. Recent advances in machine learning provide ways for fitting generative models without the need to evaluate the likelihood and its gradient. Generative Adversarial Networks (GAN) provide one such framework which has been successful in traditional machine learning tasks. We apply this approach in two separate experiments, showing how GANs can be used to fit commonly used mechanistic models in theoretical neuroscience to datasets of measured tuning curves. This fitting procedure avoids the computationally expensive step of inferring latent variables,e.g., the biophysical parameters of individual cells or the particular realization of the full synaptic connectivity matrix, and directly learns model parameters which characterize thestatisticsof connectivity or of single-cell properties. Another strength of this approach is that it fits the entire, joint distribution of experimental tuning curves, instead of matching a few summary statistics pickeda prioriby the user. More generally, this framework opens the door to fitting theoretically motivated dynamical network models directly to simultaneously or non-simultaneously recorded neural responses.
Metabolism constrains bird and mammal ranges and predicts shifts in response to climate change
Authors: Buckley Lauren B. , Khaliq Imran , Swanson David L. , Hof Christian
Published: July 2017

Aim

We test whether physiological constraints on maximum metabolic rate and the factor by which endotherms can elevate their metabolism (metabolic expansibility) govern cold range limits for mammal and bird species.

Location

Global

Methods

We examine metabolic expansibility at the cold range boundary (MEcrb) and its trait predictors and then use MEcrbto project range shifts for 210 mammal and 61 bird species.

Results

We find evidence for metabolic constraints: the distributions of metabolic expansibility at the cold range boundary peak at similar values for birds (2.7) and mammals (3.2). The right skewed distributions suggest some species have adapted to elevate or evade metabolic constraints. Mammals exhibit greater skew than birds, consistent with their diverse thermoregulatory adaptations and behaviors. Mammal and bird species that are small and occupy low trophic levels exhibit high levels of MEcrb. Mammals with high MEcrbtend to hibernate or use torpor. Predicted metabolic rates at the cold range boundaries represent large energetic expenditures (>50% of maximum metabolic rates). We project species to shift their cold range boundaries poleward by an average of 3.9° latitude by 2070.

Main conclusions

Our analysis suggests that metabolic constraints provide a viable mechanism for projecting cold range boundaries and range shifts in response to climate change for endotherms.
Crystal structure of hexamethyl 4,4′,4′′,4′′′,4′′′',4′′′''-[(1,3,5,2λ5,4λ5,6λ5-triazatriphosphinine-2,2,4,4,6,6-hexayl)hexakis(oxy)]hexabenzoate
Authors: Zhu Jing , Hou Guo Hui , Li Qian , Zheng Fu Wei , Wei Hong Liang , Chu Hui Juan , Wang Gang , He Juan , Qu Ling Bo
Published: July 2017

The title compound, C48H42N3O18P3, achieved in a two-step synthesis, comprises a cyclotriphosphazene core and six 4-methoxycarbonylphenoxy groups. Each P atom is attached to two substituents located up and down with respect to the plane of the phosphazene ring, the central P3N3 ring having a twist-boat conformation. The three O/P/O planes and five of the six benzene rings are nearly perpendicular to the mean plane through the phosphazene ring [dihedral angles = 82.98 (8)–88.92 (8)°], while the remaining benzene ring forms a dihedral angle of 25.72 (7)°. The crystal packing is stabilized by van der Waals interactions only.
Bis(lysine-κ2
N,O)hexa-μ2-oxido-hexaoxidobis(1,10-phenanthroline-κ2
N,N′)dicopper(II)tetravanadium(V) tetrahydrate
Authors: Giron-Moreno Ana Karen , Lara-Sánchez Nancy , Moreno-Martínez Gabriela , Pastor-Ramírez Cándida , Sánchez-Lara Eduardo , Sánchez-Morales Nailea Karina
Published: July 2017

The heterometallic coordination compound [Cu(Lys)(phen)]2V4O12·4H2O (Lys is the amino acid lysine, C6H14N2O2, and phen is 1,10-phenanthroline, C12H8N2) lies across an inversion centre. Two [Cu(Lys)(phen)]2+ units coordinate to the cyclo-vanadate fragment and the formula unit is completed by four solvent water molecules. The lysine ligand is in the zwitterionic form and chelates the CuII atom via the α-NH2 and α-COO− donor groups, while the ∊-NH3
+ group is involved in intramolecular hydrogen bonds with the central [V4O12]4− core and with solvent water molecules. In the crystal, N—H...O and O—H...O hydrogen bonds connect the components of the structure to form a three-dimensional network. The crystal structure is further stabilized by π–π interactions involving the phen ligands. The lysine group is disordered over two sets of sites with refined occupancies of 0.534 (11) and 0.466 (11).
Corporate boards, monitoring and securities class actions: a pitch
Authors: Clout Victoria J.
Published: July 2017

Purpose

The purpose of this paper is to apply Faff’s (2015) pitch template to a regulatory financial accounting research topic. The author describes her personal reflections on completing the pitch template for this project by investigating corporate boards, monitoring and securities class actions (SCAs) in Australia. The author builds on prior research in this area (Chapple et al., 2014). This study is set within prior literature examining capital markets, corporate governance, continuous disclosure regime and regulatory changes. The market reaction to corporate board changes pre- and post-SCAs is the focus of the examination within the pitch template. The pitch letter contributes to prior literature, as it demonstrates a team with established researchers using the pitch template, while prior papers have documented PhD student usage of the pitch template.

Design/methodology/approach

The author uses the Faff (2015) pitch template to focus the research team’s ideas into a concisely focused research idea. An earlier version of this pitch was presented at the Centre for International Finance and Regulation Pitching Research Symposium on 29 May 2015 in Sydney to a panel of distinguished professors and participants from market regulators including the Australian Securities and Investments Commission, Reserve Bank of Australia, Australian Prudential Regulation Authority and the financial sector including Colonial First State.

Findings

It was found that there are benefits to using the pitch template for both established and emerging researchers. Prior pitch papers have primarily been authored by PhD students. This paper’s aim was to provide evidence that established as well as emerging scholars can benefit from completing the Faff pitch template.

Originality/value

This pitch letter contributes to the research community, as it shows the process and personal reflections on undertaking the pitch exercise by a team including established and emerging researchers. Within this pitch letter there is a documentation of how the research team for the underlying project was formed and the prior experiences of the team.
Dynamic marketing capabilities, foreign ownership modes, sub-national locations and the performance of foreign affiliates in developing economies
Authors: Konwar Ziko , Papageorgiadis Nikolaos , Ahammad Mohammad Faisal , Tian Yumiao , McDonald Frank , Wang Chengang
Published: July 2017

Purpose

The purpose of this paper is to examine the role of dynamic marketing capabilities (DMC), foreign ownership modes and sub-national locations on the performance of foreign-owned affiliates (FOAs) in developing economies.

Design/methodology/approach

Based on a sample of 254 FOAs in the Indian manufacturing sector (covering the period of 2000-2008 leading to 623 firm-year observations), the empirical paper adopts the panel data regression approach.

Findings

The study confirms the significant importance of DMC to assist FOAs to gain better sales performance in an emerging market such as India. The findings indicate that wholly owned foreign affiliates (WOFAs) have better sales performance than international joint ventures (IJVs), and majority-owned international joint ventures (MAIJVs) perform better than minority-owned international joint ventures in the Indian manufacturing sector. The results confirm that effective deployment of DMC leads to better sales performance in WOFAs and to some extent in MAIJVs. Perhaps the most interesting finding is that developing DMC in non-metropolitan areas is associated with higher sales growth than in metropolitan locations.

Originality/value

The study contributes to the literature by examining the impact of DMC on performance of FOA by considering the organised manufacturing sector in a large and fast growing developing economy. In addition, the results for the moderating effects provide novel evidence of the conditions under which DMC of FOA interact with different ownership modes and influence firm performance.
The characteristics to consider in municipal shared spaces
Authors: Brinkoe Rikke , Nielsen Susanne Balslev
Published: July 2017

Purpose

The purpose of this study is through collaboration with practitioners to identify key characteristics of municipal shared spaces and, based on these, developing a guide for establishing a shared space in a municipal real-estate portfolio.

Design/methodology/approach

This paper builds on existing theory on the subject of shared space as well as the practical experience of professionals within the fields of property management, space management and facilities management. The guide presented is the result of data collected through case studies, interviews, surveys and literature reviews. This knowledge is combined with data collected through a workshop with practitioners from municipalities and the private sector, to provide a final guide that is directly applicable as a tool for working with shared space as a part of a property management strategy.

Findings

The result presented is a guide to establishing a shared space in a municipal real-estate portfolio, created in collaboration between researchers and practitioners. It provides an introduction to the topic and outlines a number of tasks that must be completed in different parts of a project, thereby providing a tool which practitioners can use to realise shared space as a strategy in the context of public real-estate management.

Originality/value

The guide presented is a first in connecting theory with practical application and through collaboration between researchers and practitioners, creating a tool to be used when working with shared space in a municipal real-estate portfolio.
Analysis of value at risk of Sukuk and conventional bonds in Pakistan
Authors: Nasir Adeel , Farooq Umar
Published: July 2017

Purpose

The purpose of this paper is to provide empirical evidence that Sukuk are different from conventional bonds from risk perspective. This study is about the comparative risk analysis of Sukuk and conventional bonds in Pakistan.

Design/methodology/approach

Sample consists of 15 Sukuk and 30 Term Finance Certificates issued in Pakistan. Value at risk is deployed by using delta normal approach to calculate risk. Two portfolios are formed separately with equal investment of ₹3m to explore the maximum loss an investor would have in portfolio of Sukuk and conventional bonds separately.

Findings

Results revealed that Sukuk are less risky and more stable instrument as compared to conventional bonds. Risk and stability of Sukuk are explained with diversification theory and liquidity perspective. It is found that correlation among most of Sukuk securities are less or negative, which help in diversifying their risk. However, the attribute of stability can be due to the few days of trading in case of Sukuk comparatively.

Originality/value

Literature has explored the operational differences between conventional and Islamic bonds on theoretical basis. However, few studies explain their differences empirically especially with respect to risk in case of Pakistan where debt market is developing. Therefore, the originality of this research lies within its comparative investigation of risk for two securities that are different from their operational perspectives.
Hardness testing of lead-free solders: a review
Authors: Yahaya Muhamad Zamri , Mohamad Ahmad Azmin
Published: July 2017

Purpose

This paper aims to cover the recent (2010-2016) techniques for carrying out hardness evaluation on lead-free solders. Details testing configuration/design were compiled and discussed accordingly to each of the measurement techniques: Vickers microhardness, Brinell microhardness and nanoindentation.

Design/methodology/approach

A brief introduction on lead-free solders and the concept of hardness testing has been described at the beginning of the review. Equipment setup, capabilities, test configuration and outcomes were presented for each technique and discussed in parallel along with the case studies from selected articles.

Findings

Comparison, outcomes and insight regarding each of the methods were highlighted to observe the recent trends, scientific challenges, limitations and probable breakthroughs of the particular hardness testing methods.

Originality/value

The compilation of latest reports, technical setup plus with the critics and perception from the authors are the main key value in this review. This provides an in-depth understanding and guidance for conducting hardness evaluation on lead-free solders.
Severe subcutaneous hematoma in a patient with psoriatic arthritis: Changes of platelet count in psoriatic patients with biologic agents
Authors: Maya Yuka , Fujita Yasuyuki , Nakayama Chihiro , Kitamura Shinya , Hata Hiroo , Arita Ken , Shimizu Hiroshi
Published: July 2017

The effectiveness of biologics has changed therapeutic strategies for psoriasis dramatically, but biologics are known to have various adverse effects. We report a 63‐year‐old woman with psoriatic arthritis who suddenly developed a subcutaneous hematoma after being successfully treated with adalimumab. As she had also suffered from alcoholic cirrhosis, we speculated that she had developed thrombocytopenia severe enough to cause a subcutaneous hematoma. Furthermore, we investigated the changes of platelet counts in 65 psoriatic patients treated with biologics at a single institute from 2010 to 2016. Platelet counts were found to have decreased by 17.4 ± 2.8% during adalimumab therapy (n = 16), 18.5 ± 3.8% during infliximab therapy (n = 17), 14.8 ± 2.1% during ustekinumab therapy (n = 20) and 18.5 ± 5.1% during secukinumab therapy (n = 12). Platelet counts decrease after the administration of biologics in accordance with disease activity, and there is the potential risk of subcutaneous hematoma and other adverse effects. When administrating biologics to psoriatic patients, especially to those with chronic liver disease, dermatologists should carefully monitor for thrombocytopenia.
Measuring changes in fracture properties from temporal variations in anisotropic attenuation of microseismic waveforms
Authors: Usher P. J. , Kendall J.‐M. , Kelly C. M. , Rietbrock A.
Published: July 2017

We investigate fracture‐induced attenuation anisotropy in a cluster of events from a microseismic dataset acquired during hydraulic fracture stimulation. The dataset contains 888 events of magnitude −3.0 to 0.0. We use a log‐spectral‐amplitude‐ratio method to estimate change in over a half‐hour time period where fluid is being injected and an increase in fracturing from S‐wave splitting analysis has been previously inferred. A Pearson's correlation analysis is used to assess whether or not changes in attenuation with time are statistically significant. P‐waves show no systematic change in during this time. In contrast, S‐waves polarised perpendicular to the fractures show a clear and statistically significant increase with time, whereas S‐waves polarised parallel to the fractures show a weak negative trend. We also compare between the two S‐waves, finding an increase in with time. A poroelastic rock physics model of fracture‐induced attenuation anisotropy is used to interpret the results. This model suggests that the observed changes in t* are related to an increase in fracture density of up to 0.04. This is much higher than previous estimates of 0.025 ± 0.002 based on S‐wave velocity anisotropy, but there is considerably more scatter in the attenuation measurements. This could be due to the added sensitivity of attenuation measurement to non‐aligned fractures, fracture shape, and fluid properties. Nevertheless, this pilot study shows that attenuation measurements are sensitive to fracture properties such as fracture density and aspect ratio.
Ventana immunohistochemistry assay for anaplastic lymphoma kinase gene rearrangement detection in patients with non‐small cell lung cancer: A meta‐analysis
Authors: Zhiwei Wang , Yuan Jiang , Yihui Yao , Xin Hou , Jingtao Chen , Lei Shi , Yongjian Duan
Published: July 2017

Background

The aim of this study was to evaluate the diagnostic value of Ventana immunohistochemistry (IHC) assay for anaplastic lymphoma kinase (ALK) gene rearrangement screening in patients with non‐small cell lung cancer (NSCLC).

Methods

Open published studies that reported the diagnostic performance of Ventana IHC assay for ALK gene rearrangement detection in NSCLC patients were extracted from PubMed, Embase, Google scholar, Wanfang, and China National Knowledge Infrastructure. The general information and number of true positive (tp), false positive (fp), false negative (fn), and true negative (tn) cases identified by Ventana IHC assay were extracted. The diagnostic sensitivity, specificity, positive likelihood ratio (+lr), negative likelihood ratio (−lr), diagnostic odds ratio (dor) and the summary receiver operating characteristic (ROC) curve were calculated using Stata 11.0 software.

Results

Ten studies, including 240 ALK positive and 1973 ALK negative NSCLC patients were included in this meta‐analysis. The pooled diagnostic sensitivity, specificity, +lr, −lr, and dor were 0.94 (95% confidence interval [CI] 0.85–0.98), 1.00 (95% CI 0.99–1.00), 859.61 (95% CI 60.81–1200.00), 0.06 (95% CI 0.03–0.16), and 1400.00 (95% CI 813.29–23 000.00), respectively. The area under the ROC curve was 0.996 for Ventana IHC assay in detecting ALK gene rearrangement in NSCLC patients.

Conclusion

The sensitivity and specificity of Ventana IHC assay for the detection of ALK gene rearrangement were high, thus Ventana IHC could substitute fluorescence in situ hybridization for the screening of ALK+ NSCLC patients.
Influence of lateral position and pneumoperitoneum on oropharyngeal leak pressure with two types of laryngeal mask airways
Authors: Lan S. , Zhou Y. , Li J. T. , Zhao Z. Z. , Liu Y.
Published: July 2017

Background

An important parameter to monitor adequate ventilation for laryngeal mask airway (LMA) is its oropharyngeal leak pressure (OLP). This study was designed to evaluate and compare the effect of lateral position and pneumoperitoneum on the OLP and ventilation efficiency between LMA™ Proseal (PLMA) and LMA™ Supreme (SLMA).

Methods

Patients were randomized to receive either the PLMA or the SMLA. The OLP was assessed in both the supine position and the lateral position with or without pneumoperitoneum. Minute ventilation was increased to maintain normal EtCO2 as far as possible. Ventilatory efficiency was scored as Class I (optimal, EtCO2 35–45 mmHg), Class II (suboptimal, EtCO2 45–55 mmHg) and Class III (poor, EtCO2 >55 mmHg). Adverse events associated with LMA such as blood staining on the mask and sore throat were also recorded.

Results

Within each group, the OLP was higher in the supine position than that in the lateral position with or without pneumoperitoneum (P < 0.01). However, pneumoperitoneum did not further decrease the OLP. The OLP with PLMA was higher compared with SLMA regardless of the position and pneumoperitoneum (P < 0.05 or 0.01). There was no significant difference in the number of patients in Class I/II/III for ventilation scores in the lateral position with pneumoperitoneum (83/7/2 in PLMA group and 76/14/2 in SLMA group, respectively). The incidence of adverse events was comparable in both groups.

Conclusion

Our data demonstrate that the PLMA has a higher OLP in comparison with the SLMA in the lateral position for laparoscopic surgery. Both devices provide comparably adequate ventilatory efficiency.
Thermal suit in preventing unintentional intraoperative hypothermia during general anaesthesia: a randomized controlled trial
Authors: Lauronen S.‐L. , Kalliomäki M.‐L. , Aho A. J. , Kalliovalkama J. , Riikonen J. M. , Mäkinen M.‐T. , Leppikangas H. M. , Yli‐Hankala A. M.
Published: July 2017

Background

Unintentional perioperative hypothermia causes serious adverse effects to surgical patients. Thermal suit (T‐Balance®) is an option for passive warming perioperatively. We hypothesized that the thermal suit will not maintain normothermia more efficiently than conventional cotton clothes when also other preventive procedures against unintentional hypothermia are used.

Methods

One hundred patients were recruited to this prospective, randomized trial. They were allocated to the Thermal Suit group or a Control group wearing conventional hospital cotton clothes. All patients received our institution's standard treatment against unintentional hypothermia including a warming mattress, a forced‐air upper body warming blanket and a warming device for intravenous fluids. Eardrum temperature was measured pre‐operatively. In the operating room and post‐anaesthesia care unit temperatures were measured from four locations: oesophagus, left axilla, dorsal surface of the left middle finger and dorsum of the left foot. The primary outcome measure was temperature change during robotic‐assisted laparoscopic radical prostatectomy.

Results

The temperatures of 96 patients were analysed. There was no difference in mean core temperatures, axillary temperatures or skin temperatures on the finger between the groups. Only foot dorsum temperatures were significantly lower in the Thermal Suit group. Intraoperative temperature changes were similar in both groups. In the post‐anaesthesia care unit temperature changes were minimal and they did not differ between the groups.

Conclusion

Provided that standard preventive procedures in maintaining normothermia are effective the thermal suit does not provide any additional benefit over conventional cotton clothes during robotic‐assisted laparoscopic radical prostatectomy.
Depression and Anxiety Among Emergency Department Patients: Utilization and Barriers to Care
Authors: Abar Beau , Holub Ashley , Lee Joseph , DeRienzo Vincent , Nobay Flavia
Published: July 2017

Background

Anxiety and depression rates among emergency department (ED) patients are substantially higher than those in the general population. Additionally, those with mental health issues often have difficulty accessing care. Unfortunately, issues of anxiety and depression are frequently not addressed in the ED due to competing care priorities. This may lead to increased burden and overcrowding in EDs.

Objective

This study related anxiety and depression with ED utilization and perceived barriers to care.

Methods

To limit the impact of insurance coverage on ED utilization and access to care, a convenience sample of adults 45 to 85 years of age in the ED were surveyed. The Generalized Anxiety Disorder 7 and Patient Health Questionnaire 9 were used to measure anxiety and depression.

Results

A total of 251 subjects were enrolled. Severe anxiety was observed in 10% of patients, while moderately severe or severe depression was observed in 12%. Patients who were both severely anxious and depressed visited the ED nearly twice as often as nonanxious and nondepressed patients. The majority of patients cited at least one moderate barrier to care, and greater anxiety and depression scores were related to greater perceived barriers to care. Perceived barriers to care were more than three times higher among patients who were both anxious and depressed compared to those in patients who were neither depressed nor anxious and twice as high as in those who were either depressed or anxious (p < 0.001).

Conclusion

Patients identified with internalizing mental health concerns utilize the ED at elevated rates while also reporting the greatest difficulties accessing care. These findings highlight the need for ED interventions aimed at identifying patient mental health concerns, as well as perceived barriers to care, to design interventions to effectively improve continuity of care.
Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co‐twin control study
Authors: Meier Madeline H. , Caspi Avshalom , Danese Andrea , Fisher Helen L. , Houts Renate , Arseneault Louise , Moffitt Terrie E.
Published: July 2017

Aims

This study tested whether adolescents who used cannabis or met criteria for cannabis dependence showed neuropsychological impairment prior to cannabis initiation and neuropsychological decline from before to after cannabis initiation.

Design

A longitudinal co‐twin control study.

Setting and Participants

Participants were 1989 twins from the Environmental Risk (E‐Risk) Longitudinal Twin Study, a nationally representative birth cohort of twins born in England and Wales from 1994 to 1995.

Measurements

Frequency of cannabis use and cannabis dependence were assessed at age 18. Intelligence quotient (IQ) was obtained at ages 5, 12 and 18. Executive functions were assessed at age 18.

Findings

Compared with adolescents who did not use cannabis, adolescents who used cannabis had lower IQ in childhood prior to cannabis initiation and lower IQ at age 18, but there was little evidence that cannabis use was associated with IQ decline from ages 12–18. For example, adolescents with cannabis dependence had age 12 and age 18 IQ scores that were 5.61 (t = −3.11, P = 0.002) and 7.34 IQ points (t = −5.27, P < 0.001) lower than adolescents without cannabis dependence, but adolescents with cannabis dependence did not show greater IQ decline from age 12–18 (t = −1.27, P = 0.20). Moreover, adolescents who used cannabis had poorer executive functions at age 18 than adolescents who did not use cannabis, but these associations were generally not apparent within twin pairs. For example, twins who used cannabis more frequently than their co‐twin performed similarly to their co‐twin on five of six executive function tests (Ps > 0.10). The one exception was that twins who used cannabis more frequently than their co‐twin performed worse on one working memory test (Spatial Span reversed; β = −0.07, P = 0.036).

Conclusions

Short‐term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests.
Major life events and risk of alcohol use disorders: a prospective cohort study
Authors: Just‐Østergaard Emilie , Mortensen Erik L. , Flensborg‐Madsen Trine
Published: July 2017

Aims

To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD).

Design

Prospective cohort study with baseline examination in 1991–93 and linkage to national registers to identify AUD at follow‐up.

Setting

Copenhagen, Denmark.

Participants

Individuals (aged 21–93 years) who participated in the Copenhagen City Heart Study in 1991–93 (n = 8758).

Measurements

The primary outcome was first registration with AUD during follow‐up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity.

Findings

Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD.

Conclusions

Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.
Scaling‐up HCV prevention and treatment interventions in rural United States—model projections for tackling an increasing epidemic
Authors: Fraser Hannah , Zibbell Jon , Hoerger Thomas , Hariri Susan , Vellozzi Claudia , Martin Natasha K. , Kral Alex H. , Hickman Matthew , Ward John W. , Vickerman Peter
Published: July 2017

Background and aims

Effective strategies are needed to address dramatic increases in hepatitis C virus (HCV) infection among people who inject drugs (PWID) in rural settings of the United States. We determined the required scale‐up of HCV treatment with or without scale‐up of HCV prevention interventions to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025 and 2030 in a rural US setting.

Design

An ordinary differential equation model of HCV transmission calibrated to HCV epidemiological data obtained primarily from an HIV outbreak investigation in Indiana.

Setting

Scott County, Indiana (population 24 181), USA, a rural setting with negligible baseline interventions, increasing HCV epidemic since 2010, and 55.3% chronic HCV prevalence among PWID in 2015.

Participants

PWID.

Measurements

Required annual HCV treatments per 1000 PWID (and initial annual percentage of infections treated) to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025/30, either with or without scaling‐up syringe service programmes (SSPs) and medication‐assisted treatment (MAT) to 50% coverage. Sensitivity analyses considered whether this impact could be achieved without re‐treatment of re‐infections, and whether greater intervention scale‐up was required due to the increasing epidemic in this setting.

Findings

To achieve a 90% reduction in incidence and prevalence by 2030, without MAT and SSP scale‐up, 159 per 1000 PWID (initially 24.9% of infected PWID) need to be HCV‐treated annually. However, with MAT and SSP scaled‐up, treatment rates are halved (89 per 1000 annually or 14.5%). To reach the same target by 2025 with MAT and SSP scaled‐up, 121 per 1000 PWID (19.9%) need treatment annually. These treatment requirements are threefold higher than if the epidemic was stable, and the impact targets are unattainable without retreatment.

Conclusions

Combined scale‐up of hepatitis C virus treatment and prevention interventions is needed to decrease the increasing burden of hepatitis C virus incidence and prevalence in rural Indiana, USA, by 90% by 2025/30.
The stability of baseline‐defined categories of alcohol consumption during the adult life‐course: a 28‐year prospective cohort study
Authors: Knott Craig S. , Bell Steven , Britton Annie
Published: July 2017

Background and aims

Studies that report the relationship between alcohol consumption and disease risk have predominantly operationalized drinking according to a single baseline measure. The resulting assumption of longitudinal stability may be simplistic and complicate interpretation of risk estimates. This study aims to describe changes to the volume of consumption during the adult life‐course according to baseline categories of drinking.

Design

A prospective observational study.

Setting

United Kingdom.

Participants

A cohort of British civil servants totalling 6838 men and 3372 women aged 34–55 years at baseline, followed for a mean 19.1 (standard deviation = 9.5) years.

Measurements

The volume of weekly alcohol consumption was estimated from data concerning the frequency and number of drinks consumed. Baseline categories were defined: non‐current drinkers, infrequent drinkers, 0.1–50.0 g/week, 50.1–100.0 g/week, 100.1–150.0 g/week, 150.1–250.0 g/week and >250.0 g/week. For women, the highest category was defined as > 100.0 g/week. Baseline frequency was derived as ‘daily or almost daily’ and ‘not daily or almost daily’. Trajectories were estimated within baseline categories using growth curve models.

Findings

Trajectories differed between men and women, but were relatively stable within light‐to‐moderate categories of baseline consumption. Drinking was least stable within the highest categories of baseline consumption (men: > 250.0 g/week; women: > 100.0 g/week), declining by 47.0 [95% confidence interval (CI) = 40.7, 53.2] and 16.8 g/week (95% CI = 12.6, 21.0), respectively, per 10‐year increase in age. These declines were not a consequence of sudden transitions to complete abstention. Rates of decline appear greatest in older age, with trajectories converging toward moderate volumes.

Conclusion

Among UK civil servants, consumption within baseline drinking categories is generally stable during the life‐course, except among heavier baseline drinkers, for whom intakes decline with increasing age. This shift does not appear to be driven by transitions to non‐drinking. Cohorts of older people may be at particular risk of misclassifying former heavy drinkers as moderate consumers of alcohol.
Extended‐release naltrexone for methamphetamine dependence among men who have sex with men: a randomized placebo‐controlled trial
Authors: Coffin Phillip O. , Santos Glenn‐Milo , Hern Jaclyn , Vittinghoff Eric , Santos Deirdre , Matheson Tim , Colfax Grant , Batki Steven L.
Published: July 2017

Background and aims

Methamphetamine use is increasingly prevalent and associated with HIV transmission. Early‐phase human studies suggested naltrexone reduced amphetamine use among dependent individuals. We tested if extended‐release naltrexone (XRNTX) reduces methamphetamine use and associated sexual risk behaviors among high‐risk methamphetamine‐dependent men who have sex with men (MSM).

Design

Double‐blind, placebo‐controlled, randomized trial of XRTNX versus placebo over 12 weeks from 2012 to 2015.

Setting

San Francisco Department of Public Health, California, USA.

Participants

One hundred community‐recruited, sexually‐active, actively‐using methamphetamine‐dependent MSM. Mean age was 43.2 years; 96% were male, 3% transfemale, and 1% transmale; 55.0% were white, 19.0% African American, and 18.0% Latino.

Interventions

XRNTX 380 mg (n = 50) or matched placebo (n = 50) administered by gluteal injection at 4‐week intervals.

Measurements

Regression estimated average level and change in level of positive urines during the period 2–12 weeks (primary outcomes) and sexual risk behaviors (secondary outcome).

Findings

Ninety per cent of visits were completed. By intent‐to‐treat, participants assigned to XRNTX had similar differences during 2–12 weeks in methamphetamine‐positive urines as participants assigned to placebo [incidence rate ratio (IRR) = 0.95, 95% confidence interval (CI) = 0.76–1.20; Bayes factor < 0.3]. Observed urine positivity declined from 78 to 70% in the XRNTX arm and 74 to 64% in the placebo arm. Adherence to injections was 96.7% in the XRNTX arm and 91.3% in the placebo arm. Sexual risk behaviors declined similarly among participants in both arms (all P > 0.05). There were no serious adverse events related to study drug and no differences in frequency of adverse events by treatment arm.

Conclusions

Notwithstanding very high medication adherence for this study, extended‐release naltrexone does not appear to reduce methamphetamine use or sexual risk behaviors among methamphetamine‐dependent men who have sex with men compared with placebo.
Prediction of alcohol use disorder using personality disorder traits: a twin study
Authors: Rosenström Tom , Torvik Fartein Ask , Ystrom Eivind , Czajkowski Nikolai Olavi , Gillespie Nathan A. , Aggen Steven H. , Krueger Robert F. , Kendler Kenneth S. , Reichborn‐Kjennerud Ted
Published: July 2017

Background and Aims

The DSM‐IV personality disorders (PDs) are comorbid with alcohol use disorder (AUD) and with each other. It remains unclear which PD criteria are most likely to drive onset and recurrence of AUD and which are merely confounded with those criteria. We determine which individual PD criteria predict AUD and the degree of underlying genetic and/or environmental aetiology.

Design

A prospective observational twin study.

Setting

Norway 1999–2011.

Participants

A total of 2528 and 2275 Norwegian adult twins in waves 1 and 2 variable‐selection analyses, and 2785 in biometric analyses.

Measurements

DSM‐IV PDs and their 80 criteria were assessed using a structured personal interview, and AUD using the World Health Organization's Composite International Diagnostic Interview.

Findings

In a variable‐selection analysis, two PD criteria were associated with AUD even after taking all the other criteria into account: criterion 8 of antisocial PD (childhood conduct disorder) and criterion 4 of borderline PD (self‐damaging impulsive behaviours). Adjusting for each other, their respective odds ratios were 3.4 [confidence interval (CI) = 2.1–5.4] and 5.0 (CI = 3.3–7.7). Endorsement strength of the criteria was associated with AUD in a dose–response manner and they explained 5.5% of variation in AUD risk—more than the full diagnoses of antisocial and borderline PDs together (0.5%). The association between borderline criterion 4 and AUD 10 years later derived mainly from their overlapping genetic factors, whereas the association between antisocial criterion 8 and AUD 10 years later was due to both genetic and non‐genetic factors.

Conclusions

Conduct disorder and self‐harming impulsivity are the foremost risk traits for alcohol use disorder among the 80 personality disorder criteria of DSM‐IV, predicting alcohol use disorder more effectively than personality disorder diagnoses. The twin‐study analysis suggested that conduct disorder represents a joint genetic and developmental risk for alcohol use disorder and that impulsivity is a genetic risk.
Adult interest in using a hypothetical modified risk tobacco product: findings from wave 1 of the Population Assessment of Tobacco and Health Study (2013–14)
Authors: Pearson Jennifer L. , Johnson Amanda L. , Johnson Sarah E. , Stanton Cassandra A. , Villanti Andrea C. , Niaura Raymond S. , Glasser Allison M. , Wang Baoguang , Abrams David B. , Cummings K. Michael , Hyland Andrew
Published: July 2017

Background and aims

The US Family Smoking Prevention and Tobacco Control Act provides a pathway for manufacturers to market a modified risk tobacco product (MRTP). This study examines socio‐demographic and tobacco use correlates of interest in a hypothetical MRTP in a nationally representative sample of US adults.

Design

Cross sectional wave 1 data from the 2013–14 Population Assessment of Tobacco and Health (PATH) Study.

Setting

Household Audio‐Computer Assisted Self‐Interviews of US adults conducted in 2013–14.

Participants

A total of 32 320 civilian, non‐institutionalized adults in the United States.

Measurements

Interest in using a hypothetical MRTP (‘If a tobacco product made a claim that it was less harmful to health than other tobacco products, how likely would you be to use that product?’), socio‐demographics, tobacco use history and mental health and substance use problems. All estimates were weighted.

Findings

Overall, 16.7% [95% confidence interval (CI) = 16.28, 17.18] of US adults reported interest in a hypothetical MRTP. Tobacco use was associated significantly with interest in a hypothetical MRTP, with interest most common among current established smokers (54.4%; 95% CI = 53.31, 55.39) and least common among never tobacco users (3.0%; 95% CI = 2.49, 3.55). Interest in a hypothetical MRTP was associated with experimental e‐cigarette use among current experimental, current established and former smokers. Among non‐smokers, race, age, education and substance use were associated with interest in using a hypothetical MRTP.

Conclusions

Among adults in the United States, interest in using a hypothetical modified risk tobacco product is low overall, and highest among current experimental and established smokers. A small percentage of non‐smokers are interested in using a hypothetical hypothetical modified risk tobacco product.
Moving alcohol prevention research forward—Part I: introducing a complex systems paradigm
Authors: Apostolopoulos Yorghos , Lemke Michael K. , Barry Adam E. , Lich Kristen Hassmiller
Published: July 2017

Background and aims

The drinking environment is a complex system consisting of a number of heterogeneous, evolving and interacting components, which exhibit circular causality and emergent properties. These characteristics reduce the efficacy of commonly used research approaches, which typically do not account for the underlying dynamic complexity of alcohol consumption and the interdependent nature of diverse factors influencing misuse over time. We use alcohol misuse among college students in the United States as an example for framing our argument for a complex systems paradigm.

Methods

A complex systems paradigm, grounded in socio‐ecological and complex systems theories and computational modeling and simulation, is introduced. Theoretical, conceptual, methodological and analytical underpinnings of this paradigm are described in the context of college drinking prevention research.

Results

The proposed complex systems paradigm can transcend limitations of traditional approaches, thereby fostering new directions in alcohol prevention research. By conceptualizing student alcohol misuse as a complex adaptive system, computational modeling and simulation methodologies and analytical techniques can be used. Moreover, use of participatory model‐building approaches to generate simulation models can further increase stakeholder buy‐in, understanding and policymaking.

Conclusions

A complex systems paradigm for research into alcohol misuse can provide a holistic understanding of the underlying drinking environment and its long‐term trajectory, which can elucidate high‐leverage preventive interventions.