bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of Enhanced Liver Fibrosis test and comparison with transient elastography in the identification of liver fibrosis in patients with chronic hepatitis B infection
Authors: Trembling P. M. , Lampertico P. , Parkes J. , Tanwar S. , Viganò M. , Facchetti F. , Colombo M. , Rosenberg W. M.
Published: August 2013

Assessment of liver fibrosis is important in determining prognosis, disease progression and need for treatment in patients with chronic hepatitis B (CHB). Limitations to the use of liver biopsy in assessing fibrosis are well recognized, and noninvasive tests are being increasingly evaluated including transient elastography (TE) and serum markers such as the Enhanced Liver Fibrosis (ELF) test. We assessed performance of ELF and TE in detecting liver fibrosis with reference to liver histology in a cohort of patients with CHB (n = 182), and compared the performance of these modalities. Median age was 46 and mean AST 70 IU/L. Cirrhosis was reported in 20% of liver biopsies. Both modalities performed well in assessing fibrosis at all stages. Area under receiver operator characteristic (AUROC) curves for detecting METAVIR fibrosis stages F ≥ 1, F ≥ 2, F ≥ 3 and F4 were 0.77, 0.82, 0.80 and 0.83 for ELF and 0.86, 0.86, 0.90 and 0.95 for TE. TE performed significantly better in the assessment of severe fibrosis (AUROC 0.80 for ELF and 0.90 for TE, P < 0.01) and cirrhosis (0.83 for ELF and 0.95 for TE, P < 0.01). This study demonstrates that ELF has good performance in detection of liver fibrosis in patients with CHB, and when compared, TE performs better in detection of severe fibrosis/cirrhosis.
The parasite‐driven‐wedge model of parapatric speciation
Authors: Thornhill R. , Fincher C. L.
Published: August 2013

The parasite‐driven‐wedge model provides a mechanism of parapatric speciation (the evolution of adjacent species across the range of an ancestral species without allopatric separation). Regionally localized coevolutionary races between parasites and their hosts result in three locally adaptive antiparasite behaviors: mating and other social preference for local conspecifics, avoidance of nonlocal conspecifics and philopatry (limited dispersal). These three behaviors comprise behavioral immunity. They become linked within individuals through linkage disequilibrium. Genetic immunity to local parasites also links through the same genetic mechanism with the traits of behavioral immunity. These linked traits are mutually reinforcing in that as any one increases in frequency due to its adaptiveness, the others do as well. Also, preference for locals is self‐reinforcing because both the locals preferred and those preferring them have the same preference. These events create a wedge and associated boundaries that effectively fractionate and diversify the original range of a species, leading to the genesis of contiguous multiple species from one. The higher the parasite stress in a region, the greater the frequency and intensity of the parasite‐driven wedge in splitting species. We do not deny an important role for allopatric speciation, but argue that parasite‐driven parapatric processes will be relatively predominant in regions of high parasite adversity (e.g. low latitudes), leading to the high diversity of species in the regions. The fractionation of host populations through the parasite‐driven wedge also diversifies parasites, leading to even greater geographic localization of host–parasite races. Methods are discussed for empirically distinguishing parasite‐driven parapatric speciation and allopatric speciation. We hypothesize that host coevolution with beneficial symbionts may also be an engine of parapatric speciation by way of a wedge‐like process.
The Paradox of Probation: Community Supervision in the Age of Mass Incarceration
Authors: Phelps Michelle S.
Published: August 2013

After four decades of steady growth,U.S. states' prison populations finally appear to be declining, driven by a range of sentencing and policy reforms. One of the most popular reform suggestions is to expand probation supervision in lieu of incarceration. However, the classic socio‐legal literature suggests that expansions of probation instead widen the net of penal control and lead to higher incarceration rates. This article reconsiders probation in the era of mass incarceration, providing the first comprehensive evaluation of the role of probation in the build‐up of the criminal justice system. The results suggest that probation was not the primary driver of mass incarceration in most states, nor is it likely to be a simple panacea to mass incarceration. Rather, probation serves both capacities, acting as an alternative and as a net‐widener, to varying degrees across time and place. Moving beyond the question of diversion versus net widening, this article presents a new theoretical model of the probation‐prison link that examines the mechanisms underlying this dynamic. Using regression models and case studies, I analyze how states can modify the relationship between probation and imprisonment by changing sentencing outcomes and the practices of probation supervision. When combined with other key efforts, reforms to probation can be part of the movement to reverse mass incarceration.
Climate Change Litigation's Regulatory Pathways: A Comparative Analysis of the United States and Australia
Authors: Peel Jacqueline , Osofsky Hari M.
Published: August 2013

This article provides a critical next step in scholarship on climate change litigation's regulatory role. It creates a model for understanding the direct and indirect regulatory roles of this litigation. It then applies this model to the United States and Australia, two key jurisdictions for climate change lawsuits, in order to explore the regulatory pathways that this litigation has taken, is taking, and likely will take. This analysis helps to illuminate the ways in which litigation influences regulation and forms part of climate change governance.
Climate Change Litigation, Obsession and Expertise: Reflecting on the Scholarly Response toMassachusetts v.EPA
Authors: Fisher Elizabeth
Published: August 2013

Climate change litigation is an obsessive preoccupation for many legal scholars. Three different “narratives” can be identified for why scholars find such litigation important to study: litigation is a response to institutional failure, legal reasoning holds authority, and litigation is a forum for the co‐production of facts and social orders. The nature and consequences of these narratives are considered in the context of the firstU.S. Supreme Court “climate change” case—Massachusetts v.EPA(2007). This analysis has implications for both how scholars understand their expertise in this area, and how they should foster it.
A Routine Activities Analysis of White‐Collar Crime in Carbon Markets
Authors: Gibbs Carole , Cassidy Michael B. , Rivers Louie
Published: August 2013

Scholars recently called for increased analysis of opportunity structures that produce white‐collar crimes in legitimate business systems. In the current research, we use mental models, a tool from cognitive psychology, to describe opportunity structures for white‐collar crime in the European Emissions Trading System, the largest carbon market in the world. Specifically, we use routine activities theory to describe the convergence of motivated offenders and suitable targets in the absence of capable guardians in different parts of the system. Implications for utilizing routine activities theory to understand and address crime in carbon markets are discussed.
World Health Organization infant and young child feeding indicators and their associations with child anthropometry: a synthesis of recent findings
Authors: Jones Andrew D. , Ickes Scott B. , Smith Laura E. , Mbuya Mduduzi N.N. , Chasekwa Bernard , Heidkamp Rebecca A. , Menon Purnima , Zongrone Amanda A. , Stoltzfus Rebecca J.
Published: August 2013

As the World Health Organization (WHO) infant and young child feeding (IYCF) indicators are increasingly adopted, a comparison of country‐specific analyses of the indicators' associations with child growth is needed to examine the consistency of these relationships across contexts and to assess the strengths and potential limitations of the indicators. This study aims to determine cross‐country patterns of associations of each of these indicators with child stunting, wasting, height‐for‐age z‐score (HAZ) and weight‐for‐height z‐score (WHZ). Eight studies using recent Demographic and Health Surveys data from a total of nine countries in sub‐Saharan Africa (nine), Asia (three) and the Caribbean (one) were identified. The WHO indicators showed mixed associations with child anthropometric indicators across countries. Breastfeeding indicators demonstrated negative associations with HAZ, while indicators of diet diversity and overall diet quality were positively associated with HAZ in Bangladesh, Ethiopia, India and Zambia (P < 0.05). These same complementary feeding indicators did not show consistent relationships with child stunting. Exclusive breastfeeding under 6 months of age was associated with greater WHZ in Bangladesh and Zambia (P < 0.05), although CF indicators did not show strong associations with WHZ or wasting. The lack of sensitivity and specificity of many of the IYCF indicators may contribute to the inconsistent associations observed. The WHO indicators are clearly valuable tools for broadly assessing the quality of child diets and for monitoring population trends in IYCF practices over time. However, additional measures of dietary quality and quantity may be necessary to understand how specific IYCF behaviours relate to child growth faltering.
An Analysis of Sorting and Recycling of Household Waste: A neo‐Ricardian Approach
Authors: Hosoda Eiji B.
Published: August 2013

One of the most interesting but troublesome features of daily recycling is the mixture of different types of household waste and degradation of a recycled material caused by the mixture of different types of waste. This is often seen in recycling of materials such as used papers, plastics and so on. This paper analyses this aspect, and demonstrates how the formation of prices and activity levels is made in a long‐run growing economy, by means of a neo‐Ricardian type of production model. It is proved that a long‐run equilibrium exists under reasonable assumptions. It is also shown how the sorting rate of different types of waste affects the grade of recyclable resources as well as prices.
The Interaction Between Technology Adoption and Trade When Firms are Heterogeneous
Authors: Unel Bulent
Published: August 2013

This paper develops a monopolistic competition model with heterogeneous firms to study the interaction between technology adoption and trade in a world of two countries facing different technology adoption costs. It shows that a reduction in the technology adoption cost in one country increases productivity, induces more firms to adopt advanced technology, and improves welfare in this country, while decreasing productivity, inducing more firms to switch back to old technology, and reducing welfare in the other country. Furthermore, although a reduction in transport costs always makes the country with the lower adoption cost better off, it can hurt the other country.
Clinical and Genetic Features of 5 Chinese Patients with X‐linked lymphoproliferative Syndrome
Authors: Sun J. , Ying W. , Liu D. , Hui X. , Yu Y. , Wang J. , Wang X.
Published: August 2013

In this study, we report the clinical and genetic features of Chinese patients with X‐linked lymphoproliferative syndrome (XLP). Male patients with fulminant infectious mononucleosis (FIM), Epstein–Barr virus (EBV)‐associated hemophagocytic lymphohistiocytosis (HLH) or persistent EBV viremia were enrolled in this study. Direct sequencing was used to detect SH2D1A/XIAP gene mutations. The patients' clinical features were assessed by retrieval of data from medical records. Twenty‐one male patients with FIM, EBV‐associated HLH or persistent EBV viremia were evaluated. Four patients had SH2D1A mutations, and one patient had an XIAP mutation. All five of these patients had symptoms of HLH and EBV infection. Among the five patients, the youngest one was only 1 month old at onset. One patient exhibited hypogammaglobulinemia. Of four patients evaluated for immunological function, all exhibited reduced CD4/CD8 ratios. Three patients had rapid disease progression and died. One patient received haematopoietic stem cell transplantation and is well. The overall clinical phenotypes of Chinese patients with XLP matched previous reports. For patients with severe EBV‐associated HLH, our results indicate the need to examine the possibility of XLP.
Identification of binding domains on red blood cell glycophorins for Babesia divergens
Authors: Cursino‐Santos Jeny R. , Halverson Greg , Rodriguez Marilis , Narla Mohandas , Lobo Cheryl A.
Published: August 2013

Background

Invasion of red blood cells (RBCs) is one of the critical points in the lifecycle of Babesia. The parasite does not invade other host cells. Earlier work has shown that GPA and GPB function as putative receptors during parasite invasion. The primary focus of this study was the delineation of parasite‐binding domains on GPA and GPB.

Study Design and Methods

The assay of choice to validate molecules that participate in invasion is an inhibition of invasion assay, in which changes in parasitemia are assessed relative to a wild‐type assay (no inhibitors). Inhibition of invasion can be achieved by modification of different components of the assay or by the addition of competitors of the molecules that participate in invasion. In this study purified antibody fragments to various domains on GPA and GPB were tested for magnitude of inhibition of parasite invasion. Effects on invasion were monitored by assessment of Giemsa‐stained smears every 24 hours.

Results

Among 10 selected antibodies directed at various epitopes on GPA and GPB, antibodies directed against GPAM epitopes had the most severe effect (up to 35%) on inhibition of invasion, followed by antibodies directed against GPBS epitope (up to 24%).

Conclusion

This study confirms the role of RBC glycophorins A and B in Babesia divergens invasion and shows that the GPAM and GPBS epitopes are likely to play an important role in the entry process.
Evaluating Pesticide Degradation in the Environment: Blind Spots and Emerging Opportunities
Authors: Fenner Kathrin , Canonica Silvio , Wackett Lawrence P. , Elsner Martin
Published: August 2013

The benefits of global pesticide use come at the cost of their widespread occurrence in the environment. An array of abiotic and biotic transformations effectively removes pesticides from the environment, but may give rise to potentially hazardous transformation products. Despite a large body of pesticide degradation data from regulatory testing and decades of pesticide research, it remains difficult to anticipate the extent and pathways of pesticide degradation under specific field conditions. Here, we review the major scientific challenges in doing so and discuss emerging opportunities to identify pesticide degradation processes in the field.
Wildlife Ecotoxicology of Pesticides: Can We Track Effects to the Population Level and Beyond?
Authors: Köhler Heinz-R. , Triebskorn Rita
Published: August 2013

During the past 50 years, the human population has more than doubled and global agricultural production has similarly risen. However, the productive arable area has increased by just 10%; thus the increased use of pesticides has been a consequence of the demands of human population growth, and its impact has reached global significance. Although we often know a pesticide′s mode of action in the target species, we still largely do not understand the full impact of unintended side effects on wildlife, particularly at higher levels of biological organization: populations, communities, and ecosystems. In these times of regional and global species declines, we are challenged with the task of causally linking knowledge about the molecular actions of pesticides to their possible interference with biological processes, in order to develop reliable predictions about the consequences of pesticide use, and misuse, in a rapidly changing world.
Earliest Evolution of Multituberculate Mammals Revealed by a New Jurassic Fossil
Authors: Yuan Chong-Xi , Ji Qiang , Meng Qing-Jin , Tabrum Alan R. , Luo Zhe-Xi
Published: August 2013

Early Multi

Multituberculate mammals (multis) first arose in the Jurassic and became extinct in the Oligocene, a span of over 100 million years, which makes them the longest-living order of mammals known. This highly diverse and abundant group filled many niches occupied by today's similarly diverse rodents. Multis are known for their complex dentition and unique locomotor adaptations, which facilitated their divergence into a suite of ecosystems.

Yuan
et al.

(p.
779
) describe a new basal multi from a nearly complete skeleton that shows that the underpinnings of these adaptations arose early in the evolution of the order, setting the stage for the major diversification and radiation of the group that came during the Cretaceous and Paleogene.
Earthquake Risk in Turkey
Authors: Erdik Mustafa
Published: August 2013

Recent efforts are helping to increase earthquake preparedness in a region of high earthquake risk.
Incision into the Eastern Andean Plateau During Pliocene Cooling
Authors: Lease Richard O. , Ehlers Todd A.
Published: August 2013

Bringing Down the Andes

Mountain ranges, like the Andes in South America, have a number of forces acting on them that control their elevation. High rates of precipitation can induce rapid incision of canyons, but tectonic forces from deep within the mountain range may balance or even exceed the rate of erosion.
Lease and Ehlers
(p.
774
) examined the exhumation histories of the northeastern Andean Plateau. The erosion of sediments older than ∼10 million years was controlled largely by tectonic processes. However, more recent sediments suggest that a shift to cooler temperatures increased precipitation 3 to 4 million years ago.
Cleavage of Fibrinogen by Proteinases Elicits Allergic Responses Through Toll-Like Receptor 4
Authors: Millien Valentine Ongeri , Lu Wen , Shaw Joanne , Yuan Xiaoyi , Mak Garbo , Roberts Luz , Song Li-Zhen , Knight J. Morgan , Creighton Chad J. , Luong Amber , Kheradmand Farrah , Corry David B.
Published: August 2013

Allergy Induction

Proteinases found in fungi and other allergens elicit allergic inflammation, but how they do so is far from clear. It is also unclear how pattern recognition receptors, which detect invading microbes, drive allergic inflammation.

Millien
et al.

(p.
792
) shed light on this puzzle by showing that, in mice, induction of allergic inflammation requires proteinase-dependent cleavage of the clotting factor fibrinogen, leading to generation of a ligand that activates the pattern-recognition receptor, Toll-like receptor 4 (TLR4). Cleaved fibrinogen signals through TLR4 to activate the innate immune system and recruit cells to the airway, which drives both allergic responses and antifungal immunity.
Reevaluate Pesticides for Food Security and Safety
Authors: Verger Philippe J. P. , Boobis Alan R.
Published: August 2013

Generic pesticides, vital in the developing world, present assessment challenges.
A U.K. View on the U.S. Attack on Social Sciences
Authors: Boyle Paul
Published: August 2013

U.S. politicians should refrain from a self-defeating critique of the world's leading social science community.
Paths from Pesticides to Parkinson's
Authors: Kamel Freya
Published: August 2013

High-quality studies of specific chemical pesticides are needed to determine the relationship between exposure and risk of Parkinson's disease.
Growing Up With Pesticides
Authors: Mascarelli Amanda
Published: August 2013

Long-term studies of the effects of pesticides and other environmental chemicals on the very young brain are coming up with worrisome results.
Evaluation of the Recombinant Protein TpF1 of Treponema pallidum for Serodiagnosis of Syphilis
Authors: Jiang Chuanhao , Zhao Feijun , Xiao Jinhong , Zeng Tiebing , Yu Jian , Ma Xiaohua , Wu Haiying , Wu Yimou
Published: August 2013

Syphilis is a chronic infection caused byTreponema pallidumsubsp.pallidum, and diagnosis with sensitive and specific methods is a challenging process that is important for its prevention and treatment. In the present study, we established a recombinant protein TpF1-based indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and a Western blot assay for human and rabbit sera. The 20-kDa recombinant protein TpF1 was detected by Western blotting performed with sera from rabbits immunized with recombinant TpF1 and infected with theT. pallidumNichols strain andT. pallidumclinical isolates but was not detected by Western blotting with sera from uninfected rabbits. The sensitivity of the recombinant protein was determined by screening sera from individuals with primary, secondary, latent, and congenital syphilis (n= 82). The specificity of the recombinant protein was determined by screening sera from uninfected controls (n= 30) and individuals with potentially cross-reactive infections, including Lyme disease (n= 30) and leptospirosis (n= 5). The sensitivities of TpF1-based ELISAs were 93.3%, 100%, 100%, and 100% for primary, secondary, latent, and congenital syphilis, respectively, and the specificities were all 100% for sera from uninfected controls and individuals with potentially cross-reactive infections. In Western blot assays, the sensitivities and specificities of TpF1 for human sera were all 100%. The reactivities of TpF1 with syphilitic sera were proportional to the titers of theT. pallidumparticle agglutination (TPPA) assay. These data indicate that the recombinant protein TpF1 is a highly immunogenic protein in human and rabbit infections and a promising marker for the screening of syphilis.
Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression
Authors: Miura Mika , Maekawa Shinya , Takano Shinichi , Komatsu Nobutoshi , Tatsumi Akihisa , Asakawa Yukiko , Shindo Kuniaki , Amemiya Fumitake , Nakayama Yasuhiro , Inoue Taisuke , Sakamoto Minoru , Yamashita Atsuya , Moriishi Kohji , Enomoto Nobuyuki
Published: August 2013

Variation of core amino acid (aa) 70 of hepatitis C virus (HCV) has been shown recently to be closely correlated with liver disease progression, suggesting that the core region might be present as a quasispecies during persistent infection and that this quasispecies nature might have an influence on the progression of disease. In our investigation, the subjects were 79 patients infected with HCV genotype 1b (25 with chronic hepatitis [CH], 29 with liver cirrhosis [LC], and 25 with hepatocellular carcinoma [HCC]). Deep sequencing of the HCV core region was carried out on their sera by using a Roche 454 GS Junior pyrosequencer. Based on a plasmid containing a cloned HCV sequence (pCV-J4L6S), the background error rate associated with pyrosequencing, including the PCR procedure, was calculated as 0.092 ± 0.005/base. Deep sequencing of the core region in the clinical samples showed a mixture of “mutant-type” Q/H and “wild-type” R at the core aa 70 position in most cases (71/79 [89.9%]), and the ratio of mutant residues to R in the mixture increased as liver disease advanced to LC and HCC. Meanwhile, phylogenetic analysis of the almost-complete core region revealed that the HCV isolates differed genetically depending on the mutation status at core aa 70. We conclude that the core aa 70 mixture ratio, determined by deep sequencing, reflected the status of liver disease, demonstrating a significant association between core aa 70 and disease progression in CH patients infected with HCV genotype 1b.
Dual Split Protein-Based Fusion Assay Reveals that Mutations to Herpes Simplex Virus (HSV) Glycoprotein gB Alter the Kinetics of Cell-Cell Fusion Induced by HSV Entry Glycoproteins
Authors: Atanasiu Doina , Saw Wan Ting , Gallagher John R. , Hannah Brian P. , Matsuda Zene , Whitbeck J. Charles , Cohen Gary H. , Eisenberg Roselyn J.
Published: August 2013

Herpes simplex virus (HSV) entry and cell-cell fusion require glycoproteins gD, gH/gL, and gB. We propose that receptor-activated changes to gD cause it to activate gH/gL, which then triggers gB into an active form. We employed a dual split-protein (DSP) assay to monitor the kinetics of HSV glycoprotein-induced cell-cell fusion. This assay measures content mixing between two cells, i.e., fusion, within the same cell population in real time (minutes to hours). Titration experiments suggest that both gD and gH/gL act in a catalytic fashion to trigger gB. In fact, fusion rates are governed by the amount of gB on the cell surface. We then used the DSP assay to focus on mutants in two functional regions (FRs) of gB, FR1 and FR3. FR1 contains the fusion loops (FL1 and FL2), and FR3 encompasses the crown at the trimer top. All FL mutants initiated fusion very slowly, if at all. However, the fusion rates caused by some FL2 mutants increased over time, so that total fusion by 8 h looked much like that of the WT. Two distinct kinetic patterns, “slow and fast,” emerged for mutants in the crown of gB (FR3), again showing differences in initiation and ongoing fusion. Of note are the fusion kinetics of the gB
syn
mutant (LL871/872AA). Although this mutant was originally included as an ongoing high-rate-of-fusion control, its initiation of fusion is so rapid that it appears to be on a “hair trigger.” Thus, the DSP assay affords a unique way to examine the dynamics of HSV glycoprotein-induced cell fusion.
Efficiency of E2-p7 Processing Modulates Production of Infectious Hepatitis C Virus
Authors: Shanmugam Saravanabalaji , Yi MinKyung
Published: August 2013

Previous studies indicate that the processing of hepatitis C virus (HCV) E2-p7-NS2 precursor mediated by host signal peptidase is relatively inefficient, resulting in the accumulation of E2-p7-NS2 and E2-p7 precursors in addition to E2 in mammalian cells. In this study, we discovered that a significant inhibition of the processing at an E2-p7 junction site is detrimental for HCV production, whether it was caused by the mutations in p7 or by the strategic introduction of a mutation at a terminal residue of E2 to block the signal peptidase-mediated cleavage of this junction site. However, complete separation of E2 and p7 by inserting an encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) between these two proteins also moderately inhibited virus production. These results indicate that optimal processing of the E2-p7 junction site is critical for efficient HCV production. We further demonstrated that disrupting E2-p7 processing inhibits both NS2 localization to the putative virus assembly sites near lipid droplets (LD) and NS2 interaction with NS3 and E2. However, the impact, if any, of the p7-NS2 processing efficiency on HCV production seems relatively minor. In conclusion, these results imply that effective release of E2 and p7 from the precursor E2-p7 promotes HCV production by enhancing NS2-associated virus assembly complex formation near LD.
Human Rhinovirus Subviral A Particle Binds to Lipid Membranes over a Twofold Axis of Icosahedral Symmetry
Authors: Kumar Mohit , Blaas Dieter
Published: August 2013

Minor group human rhinoviruses bind low-density lipoprotein (LDL) receptors for endocytosis. Once they are inside endosomes, the acidic pH triggers their dissociation from the receptors and conversion into hydrophobic subviral A particles; these attach to the membrane and transfer their single-strand, positive-sense RNA genome into the cytosol. Here, we allowed human rhinovirus 2 (HRV2) A particles, produced
in vitro
by incubation at pH 5.4, to attach to liposomes; cryo-electron microscopy 3-dimensional single-particle image reconstruction revealed that they bind to the membrane around a 2-fold icosahedral symmetry axis.
Can resistance training change the strength, body composition and self-concept of overweight and obese adolescent males? A randomised controlled trial
Authors: Schranz Natasha , Tomkinson Grant , Parletta Natalie , Petkov John , Olds Tim
Published: August 2013

Background/aim

Resistance training is an exercise modality at which overweight and obese adolescents can excel and which can therefore positively affect their psychological well-being. The aim of this study was to determine the effect of a 6-month resistance training intervention on the self-concept strength and body composition of overweight and obese adolescent males.

Methods

56 overweight and obese males aged 13–17 years were randomly allocated to an Intervention (n=30) or Control (n=26) group. Primary (psychological) and secondary (strength and body composition) outcomes were assessed at baseline as well as at 3 (halfway through the intervention), 6 (immediately postintervention) and 12 months follow-up. Random effects mixed modelling was used to determine the effects of the intervention.

Results

Statistically significant differences between the Intervention and Control groups were observed at 3-month and 6-month assessments for exercise self-efficacy, resistance training confidence and self-esteem. Large increases in strength for the Intervention group, relative to Controls, were also observed with no substantial changes in body composition shown for either group. Values for all variables returned to baseline following completion of the programme.

Conclusions

A 6-month resistance training intervention can positively affect the self-concept and strength of overweight and obese adolescent boys.
Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B: systematic review and meta-analysis
Authors: Thiele Maja , Gluud Lise L , Dahl Emilie K , Krag Aleksander
Published: August 2013

Objectives

The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV.

Design

Random-effects pairwise meta-analysis of randomised trials and observational studies.

Setting

Electronic and manual searches were combined. Randomised controlled trials (RCTs) were included in the primary analyses. Observational studies were included in sensitivity analyses.

Primary and secondary outcome measures

The primary outcome measures were HCC incidence and mortality. The secondary outcome measure was HCC mortality.

Results

We included 8 RCTs, 8 prospective cohort studies and 19 case–control studies with a total of 3433 patients allocated to antiviral therapy and 4625 controls. The maximum duration of follow-up was 23 years. Randomised trials found no effect of antiviral therapy on HCC or mortality. Cohort studies found that antiviral therapy increased the risk of HCC (risk ratio 1.43; 95% CI 1.06 to 1.95), whereas case–control studies found a decreased risk of HCC in the intervention group (risk ratio 0.69; 95% CI 0.54 to 0.88). There was a clear difference between the results of RCTs and observational studies (test for subgroup differences, p<0.001). Antiviral therapy did not affect mortality in cohort studies, but reduced mortality in case–control studies (relative risk 0.71; 95% CI 0.54 to 0.93; test for subgroup differences, p=0.406).

Conclusions

The effect of antiviral therapy on clinical outcomes in HBV remains to be established. Although there was a positive effect in the sensitivity analyses, the strength of the evidence does not allow for extrapolation to clinical practice as research design plays an essential role in the overall assessment.

Trial registration number

Prospero number CRD42013003881.
070 Strategies for Health System Implementation of Guidelines on Overweight and Obesity
Authors: Abrahamian Y , Watson H
Published: August 2013

Background

Evidence-based clinical practice guidelines (CPGs) for adult obesity and overweight provide recommendations to clinicians on interventions for weight loss and maintenance. organisation-wide implementation of these guidelines is critical to achieve changes in practice and patient health outcomes.

Context

To describe novel guideline implementation strategies used by a large US health care organisation to improve the care of obese and overweight adults.

Description of Best Practice

An evidence-based CPG was developed to address management strategies for a rapidly increasing number of obese and overweight patients. Interventions aimed at practitioner, patient and systems levels were tailored to facilitate implementation of CPG recommendations. Practitioner interventions included basic knowledge dissemination via electronic distribution of CPGs, presentation of CPGs at clinician champions’ meetings; and development of point-of-care job aids, such as in-clinic access to online CPGs and office prompts to refer obese patients to weight management classes. Patient-level interventions included proactive outreach for health education classes and telephone-based coaching; point-of-care educational publications; and after-visit summaries with weight management recommendations. Interventions at the systems level included proactive office encounter recording of patient BMI and exercise regimen; clinical performance goals; reporting of health outcomes of participants in weight management programmes; and, a physician continuing medical education (CME) course. Continued improvements in clinician/patient communication about weight, collection of patient weight information, and patient health outcomes have been observed.

Lessons for Guideline Developers, Adaptors, Implementers, and/or Users

Novel approaches to integrating guidance on the management of obesity and overweight into practice can achieve significant changes in clinical practice and patient health outcomes.
072 Validation of the Guideline Implementability for Decision Excellence Model (Guide-M)
Authors: Brouwers M , Kastner M , Makarski J , Durocher L
Published: August 2013

Background

We developed a Guideline Implementability for Decision Excellence-Framework Model (GuIDE-M) based on the robust evidentiary base of a realist review on guideline attributes. GuIDE-M emerged as a conceptual representation of factors to facilitate the development of more implementable guidelines.

Objectives

Validity assessment of GuIDE-M with international guideline developers.

Methods

We assessed GuIDE-M using a stepwise validation process: Stage 1 involved consultation with a multi-disciplinary group of Canadian experts (including guideline research, psychology, management, and human factors engineering) to assess the sense and structure of the conceptual GuIDE-M. In Stage 2, 200 international guideline developers will assess GuIDE-M using an innovative online assessment platform, which includes an interactive video-based system to enable objective assessment of the model and its components.

Results

In Stage 1, consultation with 10 multi-disciplinary experts informed major structural changes (e.g., addition of a 6th domain) and minor sense changes (e.g., collapsing like attributes) to the model. Stage 2 (in progress) will assess the organisation of the model according to Stage 1 findings: 1) To consider Stakeholder involvement, Evidence synthesis, Considered judgement and Feasibility in the development of guidelines; 2) and to communicate this content using effective Language and Format.

Discussion

We are applying an innovative stepwise process to rigorously validate and refine GuIDE-M internationally.

Implications for Guideline Developers/Users

This study represents a novel contribution to guideline developers and will offer a comprehensive, validated model that considers an exhaustive set of evidence-based factors to facilitate guideline uptake.
076 Enhancing the Acceptance and Implementation of GRADE Summary Tables for Evidence about Diagnostic Tests
Authors: Mustafa R , Wiercioch W , Brozek J , Lelgemann M , Buehler D , Garg A , Bossuyt P , Schünemann H
Published: August 2013

Background

The GRADE Working Group developed Summary tables adapted to summarise and present evidence from diagnostic test accuracy (DTA) systematic reviews.

Objective

To develop guidance on what information to include in these summary tables and to determine the best method(s) for presentation for different end users, including healthcare providers, systematic reviewers and guideline developers.

Methods

We presented a number of alternative summary tables to participants. We conducted questionnaires and one-on-one user testing interviews with target end users. We presented printed copies of summary tables and asked open-ended and 7-point Likert-scale questions to obtain information about users’ understanding and preferences.

Results

All participants (n = 60) agreed that using summary tables to present results of DTA reviews is helpful. Presentation of several disease prevalence values was identified as a source of confusion. There was an overall preference for placement of sensitivity and specificity values inside summary tables to allow making a link to individual test results (TP, FN, TN, FP). A third of the participants read explanatory content in table footnotes. Two thirds of the participants noted that additional data, including adverse effects, costs, and treatment consequences, would be helpful for making appropriate conclusions and decisions about diagnostic tests.

Discussion

As results of DTA reviews are conceptually complicated, presenting the data in a clear, comprehensive, comprehensible way that is tailored to different end users is critical.

Implications for Guideline Developers/Users

We are developing a 3-layer approach, with varied content in summary tables of each layer tailored to the needs of different end users.
P011 Success and challenges from over 5 years of the National Stroke Foundation’s StrokeLink program. An example of a comprehensive implementation program linking stroke guidelines to current practice in Australia
Authors: Hill Kelvin
Published: August 2013

Can a national charity deliver a robust guideline development programme as well as a comprehensive implementation programme in the challenging federated health system of Australia? The National Stroke Foundation started coordinating national stroke guidelines in 2002 but soon realised developing guidelines, while fundamental, was only one of the many jigsaw pieces needed to see real improvements in the clinical care for stroke. The Foundation learnt from other national and international models of successful implementation programmes and embarked on closing the guidelines-practice gap for stroke by leading the first national stroke audit and then developing the ‘StrokeLink’ programme. The StrokeLink programme involves facilitated workshops of hospital based stroke teams, use of the audit data to identify gaps, consensus development processes to choosing gaps and consider barriers and enablers, assist teams to develop action plans to close the evidence-practice gaps and use audit data to assess changes in practice. This presentation will provide a real life example of what can be achieved by a small, dedicated team passionate about improving stroke care in Australia. Qualitative and quantitative results will be presented of the effects of the StrokeLink programme. In additional, elements of the Foundation’s implementation strategies, their history and future directions will be presented focusing on key barriers and enablers at both a strategic and operational level.
079 Formulating Guideline Recommendations about Important Clinical Questions with Low or Very Low Quality Evidence: The Case of Opioids for Chronic Pain
Authors: Harris J , Hegmann K , Weiss M
Published: August 2013

Background

Deaths from prescription opioids now exceed those from street drugs or motor vehicle injuries in the US. Morbidity in has greatly increased as well. Rapid acceleration of opioid prescription for chronic non-cancer pain (CNCP) began in the mid-1990s with heavy marketing and support by opioid manufacturers. Some current recommendations advocate increased use of opioids despite a lack of quality evidence of long-term efficacy, considerable evidence of harms, and a tenuous understanding of CNCP.

Objectives

To review the recommendation methodology used in cases of low quality evidence; to describe the process of recommendation development for opioid use for CNCP

Methods

The American College of Occupational and Environmental Medicine updated its systematic reviews and clinical practice guideline for the use of opioids for CNCP using critical appraisal and explicit panel methods. Panels consider population and clinical risk and benefit.

Results

Critical appraisal revealed low quality evidence. Most studies and many guideline panellists were funded by pharmaceutical companies. Harms were identified in observational studies.

Discussion

Available guidelines tended to make vague recommendations that depended on clinician judgement. This panel therefore used methods to formulate recommendations that protect patients and the public, and a conservative and function-based approach to patient management.

Implications for Guideline Developers

Guidelines for areas in which evidence is low quality and the benefit to risk relationship is unclear should exercise caution in making recommendations, provide patient information, and recommend informed consent and careful patient management.
083 Developing and Implementing a Computerised Decision Support System for General Practice in the Netherlands
Authors: Bouma M , Lugtenberg M , Dorland R , Groot R de , Pasveer D , Kool T , Burgers J
Published: August 2013

Background

The Dutch College of General Practitioners (NHG) has produced almost 100 guidelines. Guideline adherence is on average 70–75%, but varies between general practitioners and between guideline recommendations. A computerised decision support system (CDSS) could improve guideline adherence.

Objectives

To describe the development and implementation of a CDSS (NHGDoc) for general practice in the Netherlands.

Methods

NHGDoc is a collaborative effort between the NHG and ExpertDoc, the company that developed the CDSS. Relevant recommendations of eight NHG guidelines were translated into algorithms, generating specific alerts. All alerts were reviewed and authorised by guideline developers of the NHG. NHGDoc was integrated in two out of seven electronic health record systems used in Dutch general practice. Since 2008, users were regularly interviewed regarding their experiences with NHGDoc.

Results

Integration of eight guidelines in NHGDoc generated alerts in approximately 30% of all patient records. Alert frequency varied in accordance with disease prevalence. Currently, 1100 general practices (appr. 25% of Dutch general practices) are using NHGDoc. Users highly appreciated the content and lay out of the alerts, but preferred more control regarding the timing and frequency of the alerts.

Discussion

NHGDoc is well received and appreciated in general practice. To enhance the success of NHGDoc the user-friendliness of the system could be further improved. Future research should provide evidence on the effectiveness of NHGDoc in terms of improving quality of care.

Implications for Guideline Developers

To improve guideline adherence, CDSSs should have user-friendly designs, including options to personalise the decision support to meet the needs of individual users.
087 Capacities, practices and perceptions of evidence-based public health in Europe
Authors: Jansen A , Forland F , Murajda L , Latham J
Published: August 2013

Evidence-based methodologies are used to synthesise systematic high-quality evidence and were first applied in clinical practice. Evidence-based public health, however, is still in its early stages. The European Centre for Disease Prevention and Control sought the insight of European organisations working in the field of public health on current practices, capacities, perceptions and predictions of evidence-based public health. A survey was sent to 76 organisations. A response rate of 36% was achieved, representing 27 organisations from 16 countries. Systematic reviews were the most commonly offered service, followed by health technology assessments and rapid assessments. Fifty-four per cent of respondents believed that evidence-based methodologies were poorly integrated into public health. The main perceived barriers to the further development of evidence-based public health included ‘lack of formalised structure or system’, ‘resource constraints’ ‘lack of understanding of evidence-based methodologies by policy makers’ and ‘lack of data’. Nevertheless, 81% of respondents believed that evidence-based methodologies will play an increasingly important role in public health in future. However, several barriers need to be overcome. Consistent frameworks and consensus on best practices were identified as the most pressing requirements. Steps should be taken to address these barriers and facilitate integration and ultimately public health policies.
089 An international comparison of occupational guidelines for the management of mental disorders
Authors: Joosen M , Brouwers E , Beurden K van , Terluin B , Klink J van der , Verbeek J , Eguchi H , Woo J , Weeghel J van
Published: August 2013

Background

To address the problem of sickness absence due to mental disorders, guidelines have been developed in various countries.

Objectives

To assess available guidelines on the management of mental disorders in an occupational health care setting on their quality and to compare recommendations.

Methods

Guidelines were selected by systematically searching PubMed, Guidelines International Network Library, and National Guideline Clearinghouse. In addition, members of the International Commission on Occupational Health were consulted. Quality of guidelines was assessed with the AGREEII instrument and recommendations were compared.

Results

Fifteen guidelines were included: 1 Japanese, 1 Danish, 2 Finnish, 2 South-Korean, 2 British and 7 Dutch. The quality of the guidelines varied. Barriers and facilitators for implementation (Applicability), competing interests (Editorial independences), and the process to gather and synthesise evidence (Rigour of Development) were poorest described. The domain Scope and Purpose scored highest. Recommendations concerning assessment refer to diagnostic classification, inventory of performance problems, causal factors and barriers for recovery. Specific workplace factors are often mentioned. Guidelines agree on work adaptation if necessary, psychological treatment and communication about treatment plan between involved actors.

Discussion

Guidelines are difficult to find since they are commonly exclusively available in local languages. Therefore probably more guidelines exist then found. To learn from each other, guidelines should be translated into world languages and be accessible via international databases.

Implications

Guideline developers can use AGREEII to increase quality. Although social context may differ among countries and can influence guideline recommendations, developers can learn from each other through reviews of this kind.