bluuebunny/crossref_metadata_2025 huggingface dataset:
The transthyretin amyloidoses: advances in therapy
Authors: Dubrey Simon , Ackermann Elizabeth , Gillmore Julian
Published: June 2015

There are two forms of transthyretin (TTR) amyloidosis: non-hereditary and hereditary. The non-hereditary form (ATTRwt) is caused by native or wild-type TTR and was previously referred to as senile systemic amyloidosis. The hereditary form (ATTRm) is caused by variant TTR which results from a genetic mutation of TTR. The predominant effect of ATTRwt amyloidosis is on the heart, with patients having a greater left ventricular wall thickness at presentation than the devastating form which is light chain (AL) amyloidosis. ATTRm amyloidosis is broadly split into two categories: a type that predominantly affects the nervous system (often called familial amyloid polyneuropathy (FAP)) and one with a predilection for the heart (often called familial amyloid cardiomyopathy (FAC)). Approximately half of all TTR mutations known to express a clinical phenotype cause a cardiomyopathy. Since the introduction of orthotopic liver transplantation for ATTRm amyloidosis in 1991, several additional therapies have been developed. These therapies aim to provide a reduction or elimination of TTR from the plasma (through genetic approaches), stabilisation of the TTR molecule (to prevent deposition) and dissolution of the amyloid matrix. We describe the latest developments in these approaches to management, many of which are also applicable to wild-type amyloidosis.
Iontronics
Authors: Chun Honggu , Chung Taek Dong
Published: June 2015

Iontronics is an emerging technology based on sophisticated control of ions as signal carriers that bridges solid-state electronics and biological system. It is found in nature, e.g., information transduction and processing of brain in which neurons are dynamically polarized or depolarized by ion transport across cell membranes. It suggests the operating principle of aqueous circuits made of predesigned structures and functional materials that characteristically interact with ions of various charge, mobility, and affinity. Working in aqueous environments, iontronic devices offer profound implications for biocompatible or biodegradable logic circuits for sensing, ecofriendly monitoring, and brain-machine interfacing. Furthermore, iontronics based on multi-ionic carriers sheds light on futuristic biomimic information processing. In this review, we overview the historical achievements and the current state of iontronics with regard to theory, fabrication, integration, and applications, concluding with comments on where the technology may advance.
Structure Principles of CRISPR-Cas Surveillance and Effector Complexes
Authors: Tsui Tsz Kin Martin , Li Hong
Published: June 2015

The pathway of CRISPR-Cas immunity redefines the roles of RNA in the flow of genetic information and ignites excitement for next-generation gene therapy tools. CRISPR-Cas machineries offer a fascinating set of new enzyme assemblies from which one can learn principles of molecular interactions and chemical activities. The interference step of the CRISPR-Cas immunity pathway congregates proteins, RNA, and DNA into a single molecular entity that selectively destroys invading nucleic acids. Although much remains to be discovered, a picture of how the interference process takes place is emerging. This review focuses on the current structural data for the three known types of RNA-guided nucleic acid interference mechanisms. In it, we describe key features of individual complexes and we emphasize comparisons across types and along functional stages. We aim to provide readers with a set of core principles learned from the three types of interference complexes and a deep appreciation of the diversity among them.
The Pathogenesis and Therapy of Muscular Dystrophies
Authors: Guiraud Simon , Aartsma-Rus Annemieke , Vieira Natassia M. , Davies Kay E. , van Ommen Gert-Jan B. , Kunkel Louis M.
Published: June 2015

Current molecular genomic approaches to human genetic disorders have led to an explosion in the identification of the genes and their encoded proteins responsible for these disorders. The identification of the gene altered by mutations in Duchenne and Becker muscular dystrophy was one of the earliest examples of this paradigm. The nearly 30 years of research partly outlined here exemplifies the road that similar current gene discovery protocols will be expected to travel, albeit much more rapidly owing to improved diagnosis of genetic disorders and an understanding of the spectrum of mutations thought to cause them. The identification of the protein dystrophin has led to a new understanding of the muscle cell membrane and the proteins involved in membrane stability, as well as new candidate genes for additional forms of muscular dystrophy. Animal models identified with naturally occurring mutations and developed by genetic manipulation have furthered the understanding of disease progression and underlying pathology. The biochemistry and molecular analysis of patient samples have led to the different dystrophin-dependent and -independent therapies that are currently close to or in human clinical trials. The lessons learned from decades of research on dystrophin have benefited the field of human genetics.
The Great Diadema antillarum Die-Off: 30 Years Later
Authors: Lessios H.A.
Published: June 2015

In 1983–1984, the sea urchin Diadema antillarum suffered mass mortality throughout the Caribbean, Florida, and Bermuda. The demise of this herbivore contributed to a phase shift of Caribbean reefs from coral-dominated to alga-dominated communities. A compilation of published data of D. antillarum population densities shows that there has been moderate recovery since 1983, with the highest rates on islands of the eastern Caribbean. On the average the current population densities are approximately 12% of those before the die-off, apparently because of recruitment limitation, but the exact factors that are constraining the recovery are unclear. Scattered D. antillarum cohorts in some localities and aggregation of settled individuals in shallow water have created zones of higher herbivory in which juvenile coral recruitment, survivorship, and growth are higher than they are in alga-dominated areas. Unlike other stressors on Caribbean coral reefs, recent changes in D. antillarum populations progress toward aiding the recovery of coral cover.
Stable Isotope Ratios as Biomarkers of Diet for Health Research
Authors: O'Brien Diane M.
Published: June 2015

Diet is a leading modifiable risk factor for chronic disease, but it remains difficult to measure accurately due to the error and bias inherent in self-reported methods of diet assessment. Consequently, there is a pressing need for more objective biomarkers of diet for use in health research. The stable isotope ratios of light elements are a promising set of candidate biomarkers because they vary naturally and reproducibly among foods, and those variations are captured in molecules and tissues with high fidelity. Recent studies have identified valid isotopic measures of short- and long-term sugar intake, meat intake, and fish intake in specific populations. These studies provide a strong foundation for validating stable isotopic biomarkers in the general US population. Approaches to improve specificity for specific foods are needed; for example, by modeling intake using multiple stable isotope ratios or by isolating and measuring specific molecules linked to foods of interest.
Quantitative Resistance to Biotrophic Filamentous Plant Pathogens: Concepts, Misconceptions, and Mechanisms
Authors: Niks Rients E. , Qi Xiaoquan , Marcel Thierry C.
Published: June 2015

Quantitative resistance (QR) refers to a resistance that is phenotypically incomplete and is based on the joined effect of several genes, each contributing quantitatively to the level of plant defense. Often, QR remains durably effective, which is the primary driver behind the interest in it. The various terms that are used to refer to QR, such as field resistance, adult plant resistance, and basal resistance, reflect the many properties attributed to it. In this article, we discuss aspects connected to those attributions, in particular the hypothesis that much of the QR to biotrophic filamentous pathogens is basal resistance, i.e., poor suppression of PAMP-triggered defense by effectors. We discuss what role effectors play in suppressing defense or improving access to nutrients. Based on the functions of the few plant proteins identified as involved in QR, vesicle trafficking and protein/metabolite transportation are likely to be common physiological processes relevant to QR.
Torradoviruses
Authors: van der Vlugt René A.A. , Verbeek Martin , Dullemans Annette M. , Wintermantel William M. , Cuellar Wilmer J. , Fox Adrian , Thompson Jeremy R.
Published: June 2015

Torradoviruses are an example of a group of recently discovered plant viruses. The first description of Tomato torrado virus, now the type member of the newly established genus Torradovirus within the family Secoviridae, was published in 2007 and was quickly followed by findings of other torradoviruses, initially all on tomato. Their characterization led to the development of tools that allowed recognition of still other torradoviruses, only very recently found on non-tomato crops, which indicates these viruses have a much wider host range and diversity than previously believed. This review describes the characteristics of this newly emerged group of plant viruses. It looks in detail at taxonomic relationships and specific characteristics in their genomes and encoded proteins. Furthermore, it discusses their epidemiology, including host range, semipersistent transmission by whitefly vectors, and impact on diverse cropping systems.
Evolution of Plant Parasitism in the Phylum Nematoda
Authors: Quist Casper W. , Smant Geert , Helder Johannes
Published: June 2015

Within the species-rich and trophically diverse phylum Nematoda, at least four independent major lineages of plant parasites have evolved, and in at least one of these major lineages plant parasitism arose independently multiple times. Ribosomal DNA data, sequence information from nematode-produced, plant cell wall–modifying enzymes, and the morphology and origin of the style(t), a protrusible piercing device used to penetrate the plant cell wall, all suggest that facultative and obligate plant parasites originate from fungivorous ancestors. Data on the nature and diversification of plant cell wall–modifying enzymes point at multiple horizontal gene transfer events from soil bacteria to bacterivorous nematodes resulting in several distinct lineages of fungal or oomycete-feeding nematodes. Ribosomal DNA frameworks with sequence data from more than 2,700 nematode taxa combined with detailed morphological information allow for explicit hypotheses on the origin of agronomically important plant parasites, such as root-knot, cyst, and lesion nematodes.
Understanding Plant Immunity as a Surveillance System to Detect Invasion
Authors: Cook David E. , Mesarich Carl H. , Thomma Bart P.H.J.
Published: June 2015

Various conceptual models to describe the plant immune system have been presented. The most recent paradigm to gain wide acceptance in the field is often referred to as the zigzag model, which reconciles the previously formulated gene-for-gene hypothesis with the recognition of general elicitors in a single model. This review focuses on the limitations of the current paradigm of molecular plant-microbe interactions and how it too narrowly defines the plant immune system. As such, we discuss an alternative view of plant innate immunity as a system that evolves to detect invasion. This view accommodates the range from mutualistic to parasitic symbioses that plants form with diverse organisms, as well as the spectrum of ligands that the plant immune system perceives. Finally, how this view can contribute to the current practice of resistance breeding is discussed.
Genomics Spurs Rapid Advances in Our Understanding of the Biology of Vascular Wilt Pathogens in the Genus Verticillium
Authors: Klimes Anna , Dobinson Katherine F. , Thomma Bart P.H.J. , Klosterman Steven J.
Published: June 2015

The availability of genomic sequences of several Verticillium species triggered an explosion of genome-scale investigations of mechanisms fundamental to the Verticillium life cycle and disease process. Comparative genomics studies have revealed evolutionary mechanisms, such as hybridization and interchromosomal rearrangements, that have shaped these genomes. Functional analyses of a diverse group of genes encoding virulence factors indicate that successful host xylem colonization relies on specific Verticillium responses to various stresses, including nutrient deficiency and host defense–derived oxidative stress. Regulatory pathways that control responses to changes in nutrient availability also appear to positively control resting structure development. Conversely, resting structure development seems to be repressed by pathways, such as those involving effector secretion, which promote responses to host defenses. The genomics-enabled functional characterization of responses to the challenges presented by the xylem environment, accompanied by identification of novel virulence factors, has rapidly expanded our understanding of niche adaptation in Verticillium species.
Identifying and Naming Plant-Pathogenic Fungi: Past, Present, and Future
Authors: Crous Pedro W. , Hawksworth David L. , Wingfield Michael J.
Published: June 2015

Scientific names are crucial in communicating knowledge about fungi. In plant pathology, they link information regarding the biology, host range, distribution, and potential risk. Our understanding of fungal biodiversity and fungal systematics has undergone an exponential leap, incorporating genomics, web-based systems, and DNA data for rapid identification to link species to metadata. The impact of our ability to recognize hitherto unknown organisms on plant pathology and trade is enormous and continues to grow. Major challenges for phytomycology are intertwined with the Genera of Fungi project, which adds DNA barcodes to known biodiversity and corrects the application of old, established names via epi- or neotypification. Implementing the one fungus–one name system and linking names to validated type specimens, cultures, and reference sequences will provide the foundation on which the future of plant pathology and the communication of names of plant pathogens will rest.
EG-VEGF, BV8, and their receptor expression in human bronchi and their modification in cystic fibrosis: Impact of CFTR mutation (delF508)
Authors: Chauvet Sylvain , Traboulsi Wael , Thevenon Laura , Kouadri Amal , Feige Jean-Jacques , Camara Boubou , Alfaidy Nadia , Benharouga Mohamed
Published: June 2015

Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca2+ and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion.
Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis
Authors: Kirby Tyler J. , Lee Jonah D. , England Jonathan H. , Chaillou Thomas , Esser Karyn A. , McCarthy John J.
Published: June 2015

The ability of skeletal muscle to hypertrophy in response to a growth stimulus is known to be compromised in older individuals. We hypothesized that a change in the expression of protein-encoding genes in response to a hypertrophic stimulus contributes to the blunted hypertrophy observed with aging. To test this hypothesis, we determined gene expression by microarray analysis of plantaris muscle from 5- and 25-mo-old mice subjected to 1, 3, 5, 7, 10, and 14 days of synergist ablation to induce hypertrophy. Overall, 1,607 genes were identified as being differentially expressed across the time course between young and old groups; however, the difference in gene expression was modest, with cluster analysis showing a similar pattern of expression between the two groups. Despite ribosome protein gene expression being higher in the aged group, ribosome biogenesis was significantly blunted in the skeletal muscle of aged mice compared with mice young in response to the hypertrophic stimulus (50% vs. 2.5-fold, respectively). The failure to upregulate pre-47S ribosomal RNA (rRNA) expression in muscle undergoing hypertrophy of old mice indicated that rDNA transcription by RNA polymerase I was impaired. Contrary to our hypothesis, the findings of the study suggest that impaired ribosome biogenesis was a primary factor underlying the blunted hypertrophic response observed in skeletal muscle of old mice rather than dramatic differences in the expression of protein-encoding genes. The diminished increase in total RNA, pre-47S rRNA, and 28S rRNA expression in aged muscle suggest that the primary dysfunction in ribosome biogenesis occurs at the level of rRNA transcription and processing.
Independent effect of type 2 diabetes beyond characteristic comorbidities and medications on immediate but not continued knee extensor exercise hyperemia
Authors: Poitras Veronica J. , Bentley Robert F. , Hopkins-Rosseel Diana H. , LaHaye Stephen A. , Tschakovsky Michael E.
Published: June 2015

We tested the hypothesis that type 2 diabetes (T2D), when present in the characteristic constellation of comorbidities (obesity, hypertension, dyslipidemia) and medications, slows the dynamic adjustment of exercising muscle perfusion and blunts the steady state relative to that of controls matched for age, body mass index, fitness, comorbidities, and non-T2D medications. Thirteen persons with T2D and 11 who served as controls performed rhythmic single-leg isometric quadriceps exercise (rest-to-6 kg and 6-to-12 kg transitions, 5 min at each intensity). Measurements included leg blood flow (LBF, femoral artery ultrasound), mean arterial pressure (MAP, finger photoplethysmography), and leg vascular conductance (LVK, calculated). Dynamics were quantified using mean response time (MRT). Measures of amplitude were also used to compare response adjustment: the change from baseline to 1) the peak initial response (greatest 1-s average in the first 10 s; ΔLBFPIR, ΔLVKPIR) and 2) the on-transient (average from curve fit at 15, 45, and 75 s; ΔLBFON, ΔLVKON). ΔLBFPIRwas significantly blunted in T2D vs. control individuals ( P = 0.037); this was due to a tendency for reduced ΔLVKPIR( P = 0.063). In contrast, the overall response speed was not different between groups (MRT P = 0.856, ΔLBFONP = 0.150) nor was the change from baseline to steady state ( P = 0.204). ΔLBFPIR, ΔLBFON, and LBF MRT did not differ between rest-to-6 kg and 6-to-12 kg workload transitions (all P > 0.05). Despite a transient amplitude impairment at the onset of exercise, there is no robust or consistent effect of T2D on top of the comorbidities and medications typical of this population on the overall dynamic adjustment of LBF, or the steady-state levels achieved during low- or moderate-intensity exercise.
Soothing the sleeping giant: improving skeletal muscle oxygen kinetics and exercise intolerance in HFpEF
Authors: Sarma Satyam , Levine Benjamin D.
Published: June 2015

Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests “peripheral,” i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.
Exome Sequencing to Predict Neoantigens in Melanoma
Authors: Pritchard Antonia L. , Burel Julie G. , Neller Michelle A. , Hayward Nicholas K. , Lopez J. Alejandro , Fatho Martina , Lennerz Volker , Wölfel Thomas , Schmidt Christopher W.
Published: June 2015

The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to use for mutated peptide screening. Five patients were investigated, three of whom had a durable complete response (CR; 15+ years) in an autologous melanoma-pulsed dendritic cell clinical trial. We identified seven mutated antigens in total that stimulated T-effector memory cells in two of the five patients. While the procedure did not result in clinically applicable neoantigens for all patients, those identified were likely important in tumor clearance, leading to durable CR. The nature of the screening process allows results to be obtained rapidly and is easily applicable to a wide variety of different tumor types. Cancer Immunol Res; 3(9); 992–8. ©2015 AACR.
Pathology and Function of Conduction Tissue in Fabry Disease Cardiomyopathy
Authors: Frustaci Andrea , Morgante Emanuela , Russo Matteo A. , Scopelliti Fernanda , Grande Claudia , Verardo Romina , Franciosa Pasquale , Chimenti Cristina
Published: June 2015

Background—

Cardiac arrhythmias are common in Fabry disease (FD) and may occur in prehypertrophic cardiomyopathy suggesting an early compromise of conduction tissue (CT). Therefore, FD X-linked and CT may be variously involved in male and female patients with FD cardiomyopathy, affecting CT function.

Methods and Results—

Among 74 patients with endomyocardial biopsy diagnosis of FD cardiomyopathy, 13 (6 men; 7 women; mean age, 50.1±13.5 years; maximal wall thickness, 16.7±3.7 mm) had CT included in histological specimens and 6 also at electron microscopy. CT glycolipid infiltration was defined as focal, moderate, extensive, or massive, if involved ≤30%, ≤50%, >50%, or 100% of cells; identified as loosely arranged small myocytes positive to HCN4 immunostaining, supplied by a centrally placed thick-walled arteriole. CT involvement was correlated with age, sex, and α-
Gal
gene mutation. CT function was evaluated by electrophysiological study and arrhythmias at Holter registration. CT infiltration was focal/moderate in 4 women with no arrhythmias and normal electrophysiological study, extensive in 3 women with atrial or ventricular arrhythmias and short HV interval, and massive in 6 men with atrial fibrillation or ventricular arrhythmias and short HV. Short PR/AH with increased refractoriness was additionally found in 3 patients with extensive/massive CT infiltration. A male patient with the shortest HV presented infra-Hissian block during decremental atrial stimulation. There was no correlation with age, maximal wall thickness, and type of gene mutation.

Conclusions—

CT infiltration in FD cardiomyopathy is constant in men and variable in women because of skewed X-chromosome inactivation; its extensive/massive involvement causes accelerated conduction with prolonged refractoriness and electric instability.
Coronary Artery Calcium Improves Risk Assessment in Adults With a Family History of Premature Coronary Heart Disease
Authors: Patel Jaideep , Al Rifai Mahmoud , Blaha Michael J. , Budoff Matthew J. , Post Wendy S. , Polak Joseph F. , Bluemke David A. , Scheuner Maren T. , Kronmal Richard A. , Blumenthal Roger S. , Nasir Khurram , McEvoy John W.
Published: June 2015

Background—

The prognostic value of coronary artery calcium (CAC) or carotid intima-media thickness (CIMT) among asymptomatic adults with a family history (FH) of premature coronary heart disease is unclear.

Methods and Results—

Multiethnic Study of Atherosclerosis enrolled 6814 adults without known atherosclerotic cardiovascular disease (ASCVD). Hard ASCVD events were ascertained over a median follow-up of 10.2 years. We estimated adjusted-hazard ratios for CAC and CIMT categories using Cox regression, both within and across FH status groups. Improvement in discrimination with CAC or CIMT added to variables from the ASCVD pooled cohort equation was also evaluated using receiver-operating characteristic curve and likelihood ratio analysis. Of 6125 individuals (62±10 years; 47% men) who reported information on FH, 1262 (21%) had an FH of premature coronary heart disease. Among these, 104 hard ASCVD events occurred. Crude incidence rates (per 1000 person-years) for hard ASCVD were 4.4 for CAC, 0 (n=574; 46% of the sample); 8.8 for CAC, 1 to 99 (n=368); 14.9 for CAC, 100 to 399 (n=178); and 20.8 for CAC, ≥400 (n=142). Relative to CAC=0, adjusted hard ASCVD hazard ratios for each CAC category among persons with an FH were 1.64 (95% confidence interval, 0.94–2.87), 2.45 (1.31–4.58), and 2.80 (1.44–5.43), respectively. However, there was no increased adjusted hazard for hard ASCVD in high versus low CIMT categories. In participants with an FH of premature coronary heart disease, CAC improved discrimination of hard ASCVD events (
P
<0.001). However, CIMT did not discriminate ASCVD (
P
=0.70).

Conclusions—

Nearly half of individuals reporting FH have zero CAC and may receive less net benefit from aspirin or statin therapy. Among persons with an FH, CAC is a robust marker of absolute and relative risk of ASCVD, whereas CIMT is not.
Association Between Acute Kidney Injury and In-Hospital Mortality in Patients Undergoing Percutaneous Coronary Interventions
Authors: Kooiman Judith , Seth Milan , Nallamothu Brahmajee K. , Heung Michael , Humes David , Gurm Hitinder S.
Published: June 2015

Background—

Acute kidney injury (AKI) post percutaneous coronary intervention (PCI) is associated with increased mortality but both death and AKI share common risk factors. Moreover, the effect of a high contrast dose, a known modifiable risk factor for AKI, on mortality is unknown. The aim of our study was to analyze the association between AKI and in-hospital mortality post PCI after adjustment for confounding by common risk factors.

Methods and Results—

This study was performed using a regional registry of all patients undergoing PCI in Michigan. Primary end points were AKI (serum creatinine increase >0.5 mg/dL) and all-cause in-hospital mortality. Propensity matching was performed, with each AKI patient matched to 4 controls. Attributable risk fraction and the exposed index number of AKI for mortality were calculated within the propensity-matched cohort. Between 2010 and 2013, 92 317 patients underwent PCI, of whom 2141 (2.3%) developed AKI. We matched 1371/2141 patients with AKI to 5484 controls. AKI was strongly associated with mortality (odds ratio=12.52, 95% confidence interval 9.29–16.86) in the propensity-matched cohort. The attributable risk fraction for mortality of AKI was 31.4% (95% confidence interval 26.8%–37.5%), and one death could be prevented for every 9 cases of AKI successfully avoided. The independent impact of a high contrast dose at time of PCI on in-hospital mortality risk was weak (adjusted odds ratio 1.19, 95% confidence interval 0.97–1.45).

Conclusions—

Nearly one-third of the in-hospital mortality post PCI is attributable to AKI. Preventing 9 cases of AKI could potentially prevent one death. These study findings stress the need for developing effective AKI preventive strategies beyond minimization of contrast dose.
Comparison of Zotarolimus- and Everolimus-Eluting Coronary Stents
Authors: Iqbal Javaid , Serruys Patrick W. , Silber Sigmund , Kelbaek Henning , Richardt Gert , Morel Marie-Angele , Negoita Manuela , Buszman Pawel E. , Windecker Stephan
Published: June 2015

Background—

Newer-generation drug-eluting stents that release zotarolimus or everolimus have been shown to be superior to the first-generation drug-eluting stents. However, data comparing long-term safety and efficacy of zotarolimus- (ZES) and everolimus-eluting stents (EES) are limited. RESOLUTE all-comers (Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) trial compared these 2 stents and has shown that ZES was noninferior to EES at 12-month for the primary end point of target lesion failure. We report the secondary clinical outcomes at the final 5-year follow-up of this trial.

Methods and Results—

RESOLUTE all-comer clinical study is a prospective, multicentre, randomized, 2-arm, open-label, noninferiority trial with minimal exclusion criteria. Patients (n=2292) were randomly assigned to treatment with either ZES (n=1140) or EES (n=1152). Patient-oriented composite end point (combination of all-cause mortality, myocardial infarction, and any revascularizations), device-oriented composite end point (combination of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization), and major adverse cardiac events (combination of all-cause death, all myocardial infarction, emergent coronary bypass surgery, or clinically indicated target lesion revascularization) were analyzed at 5-year follow-up. The 2 groups were well-matched at baseline. Five-year follow-up data were available for 98% patients. There were no differences in patient-oriented composite end point (ZES 35.3% versus EES 32.0%,
P
=0.11), device-oriented composite end point (ZES 17.0% versus EES 16.2%,
P
=0.61), major adverse cardiac events (ZES 21.9% versus EES 21.6%,
P
=0.88), and definite/probable stent thrombosis (ZES 2.8% versus EES 1.8%,
P
=0.12).

Conclusions—

At 5-year follow-up, ZES and EES had similar efficacy and safety in a population of patients who had minimal exclusion criteria.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00617084.
Circulating Very-Long-Chain Saturated Fatty Acids and Incident Coronary Heart Disease in US Men and Women
Authors: Malik Vasanti S. , Chiuve Stephanie E. , Campos Hannia , Rimm Eric B. , Mozaffarian Dariush , Hu Frank B. , Sun Qi
Published: June 2015

Background—

Circulating very-long-chain saturated fatty acids (VLCSFAs) may play an active role in the origin of cardiometabolic diseases.

Methods and Results—

We measured 3 VLCSFAs (C20:0, C22:0, and C24:0) in plasma and erythrocytes using gas-liquid chromatography among 794 incident coronary heart disease (CHD) cases who were prospectively identified and confirmed among women in the Nurses’ Health Study (NHS; 1990–2006) and among men in the Health Professionals Follow-Up Study (HPFS; 1994–2008). A total of 1233 CHD-free controls were randomly selected and matched to cases in these 2 cohorts. Conditional logistic regression was used to estimate hazard ratios and 95% confidence intervals. Plasma VLCSFAs were correlated with favorable profiles of blood lipids, C-reactive protein, and adiponectin in the NHS and HPFS and with fasting insulin and C-peptide levels in a nationally representative US comparison population. After multivariate adjustment for lifestyle factors, body mass index, diet, and long-chain n-3 and
trans
fatty acids, total VLCSFAs in plasma were associated with a 52% decreased risk of CHD (pooled hazard ratio, 0.48; 95% confidence interval, 0.32–0.72, comparing extreme quintiles;
P
trend
<0.0001). For VLCSFAs in erythrocytes, a nonsignificant inverse trend with CHD risk was observed (pooled hazard ratio, 0.66; 95% confidence interval, 0.41–1.06, comparing extreme quintiles;
P
trend
=0.16).

Conclusions—

In US men and women, plasma VLCSFAs were independently associated with favorable profiles of blood lipids and other cardiovascular disease risk markers and a lower risk of CHD. Erythrocyte VLCSFAs were associated with nonsignificant trends of lower CHD risk. Future studies are warranted to elucidate the underlying biological mechanisms.
Business as Plan B
Authors: Thébaud Sarah
Published: June 2015

This article develops and empirically evaluates an institutional theory of gender inequalities in business start-up, ownership, and growth orientation. I argue that in contexts in which institutional arrangements such as paid leave, subsidized childcare, and part-time employment opportunities mitigate work–family conflict, women are less likely to opt for business ownership as a fallback employment strategy. As a result, women in these contexts may be relatively less well represented among entrepreneurs as a whole but more well represented in growth-oriented forms of entrepreneurship. To evaluate this claim, I analyze survey data from 24 countries over the span of eight years. Multilevel analyses show that supportive work–family institutions are associated with larger gender gaps in the odds of early-stage and established business ownership but smaller gender gaps among business owners in terms of their business size, growth aspirations, and propensity to innovate or use new technology. Consistent with my theoretical argument, women business owners are also less likely to report pursuing entrepreneurship because they lacked attractive employment options in contexts in which supportive institutions are in place. Findings suggest that institutional contexts characterized by salient work–family conflict may fuel women’s aggregate representation in business activity but reinforce their segregation into less growth-oriented (and thus lower-status) ventures.
Multiculturalisms: An overview of multicultural debates in western societies
Authors: Colombo Enzo
Published: June 2015

This article examines how debates about multiculturalism evolved in western societies. In the first part, it presents the different meanings of the term ‘multiculturalism’ when it applies to diverse types of cultural difference within society: native and sub-state national groups, discriminated groups within society and immigrants. Highlighting the polysemy of the term, three theoretical approaches to multicultural issues are introduced and critically discussed: multiculturalism as a normative issue, as an (anti) ideology and as a feature of current societies. In its central part, the article considers the different criticisms that, since the beginning of the 21st century, have called for a retreat from multiculturalism, which is accused of being a failure and which is blamed for promoting social fragmentation, parallel lives and terrorist groups. In order to assess the validity of the alleged multicultural backlash, the article analyses some important trends in current research on multicultural policies, attitudes and identities. Finally, it presents the increasing interest in the analysis of ‘everyday multiculturalism’, highlighting the processes through which cultural difference is produced and negotiated in daily interactions in urban contexts.
Inequalities, marginality and the professions
Authors: Saks Mike
Published: June 2015

Professional ideologies generally commit to addressing inequalities among clients and/or the public as part of their altruistic ethos. Sociologists of professions in the Anglo-American context have written on the extent to which this commitment is honoured by professional groups, either in a positive or more critical light. This article, however, argues that professions cannot be conceptualised as equal, homogeneous entities and are best seen as hierarchically differentiated groups based on varying forms of exclusionary social closure. As such, it reviews the literature on inequalities between professional groups from a neo-Weberian approach – which is favoured over other perspectives – through the concept of marginality, primarily using the illustrative context of health care. With particular reference to the case of complementary and alternative medicine, the article highlights that future research needs to focus more on how positions of marginality influence inequalities beyond the professions – in other words, on how inequalities within professions affect inequalities without.
Long-Term Muscle Fatigue After Standing Work
Authors: Garcia Maria-Gabriela , Läubli Thomas , Martin Bernard J.
Published: June 2015

Objective:

The aims of this study were to determine long-term fatigue effects in the lower limbs associated with standing work and to estimate possible age and gender influences.

Background:

The progressive accumulation of muscle fatigue effects is assumed to lead to musculoskeletal disorders, as fatigue generated by sustained low-level exertions exhibits long-lasting effects. However, these effects have received little attention in the lower limbs.

Method:

Fourteen men and 12 women from two different age groups simulated standing work for 5 hr including 5-min seated rest breaks and a 30-min lunch. The younger group was also tested in a control day. Muscle fatigue was quantified by electrically induced muscle twitches (muscle twitch force [MTF]), postural stability, and subjective evaluation of discomfort.

Results:

MTF showed a significant fatigue effect after standing work that persisted beyond 30 min after the end of the workday. MTF was not affected on the control day. The center of pressure displacement speed increased significantly over time after standing work but was also affected on the control day. Subjective evaluations of discomfort indicated a significant increase in perception of fatigue immediately after the end of standing work; however, this perception did not persist 30 min after. Age and gender did not influence fatigue.

Conclusion:

Objective measures show the long-term effects of muscle fatigue after 5 hr of standing work; however, this fatigue is no longer perceived after 30 min of rest postwork.

Application:

The present results suggest that occupational activities requiring prolonged standing are likely to contribute to lower-extremity and/or back disorders.
Performance management in the local public sector in France: an administrative rather than a political model
Authors: Favoreu Christophe , Carassus David , Gardey Damien , Maurel Christophe
Published: June 2015

The purpose of this research is to analyse and characterize the practices of French local authorities in the field of performance management. It sets out to do so, as a first step, by putting forward a theoretical analytical framework of the different models of local performance management. It then goes on to draw on this framework and test it empirically in order to understand the nature of the French model of local performance management. The results of our research demonstrate the existence of a French, ‘performance administration’ type model evident in the trends common to French local authorities with regard to the instrumental and methodological content and the methods of steering public performance.

Points for practitioners

The managerial and practical contributions of this research on local performance initiatives are twofold. First of all, it will provide an analytical and evaluative framework for this type of initiative, not only structured around planning, accountability and evaluation tools but also around steering methods. Second, this study makes it possible to take stock of and characterize French practices in the field and their limitations compared to more mature international practices. Thus, a local authority adopting this path can therefore draw on this study to determine the scope and structure of the tools to be rolled out, depending on their purpose, be it administrative and/or political.
Public services management and co-production in multi-level governance settings
Authors: Sicilia Mariafrancesca , Guarini Enrico , Sancino Alessandro , Andreani Martino , Ruffini Renato
Published: June 2015

From a normative stance, co-production has been recommended at all stages of the public service cycle. However, previous empirical studies on co-production have neglected the question of how to make this happen. Moreover, little attention has been paid to how co-production might occur in multi-level governance settings. The aim of this article is to fill these gaps, identifying triggers and organizational and managerial issues that could support the adoption of co-production in multi-level governance settings. The empirical analysis is based on a case study of services for autistic children. The findings highlight that co-production was prompted by inter-organizational arrangements and that trust-building among the actors played a pivotal role in nurturing a co-production approach.

Points for practitioners

From an organizational perspective, our case study shows that, in order to foster co-production in multi-level governance settings, all stages of the public service cycle should be aligned and inspired by the same logic. From a managerial perspective it highlights that the implementation of co-production requires new managerial skills and tools. Public managers are asked to listen to community groups and individuals, to mobilize collective resources and knowledge, and exercise a meta-governance role. Finally, in order to have co-produced services, our findings point to the need to start thinking differently about the roles of civil society and government in satisfying the common good.
Activating collective co-production of public services: influencing citizens to participate in complex governance mechanisms in the UK
Authors: Bovaird Tony , Stoker Gerry , Jones Tricia , Loeffler Elke , Pinilla Roncancio Monica
Published: June 2015

Previous research has suggested that citizen co-production of public services is more likely when the actions involved are easy and can be carried out individually rather than in groups. This article explores whether this holds in local areas of England and Wales. It asks which people are most likely to engage in individual and collective co-production and how people can be influenced to extend their co-production efforts by participating in more collective activities. Data were collected in five areas, using citizen panels organized by local authorities. The findings demonstrate that individual and collective co-production have rather different characteristics and correlates and highlight the importance of distinguishing between them for policy purposes. In particular, collective co-production is likely to be high in relation to any given issue when citizens have a strong sense that people can make a difference (‘political self-efficacy’). ‘Nudges’ to encourage increased co-production had only a weak effect.

Points for practitioners

Much of the potential pay-off from co-production is likely to arise from group-based activities, so activating citizens to move from individual to collective co-production may be an important issue for policy. This article shows that there is major scope for activating more collective co-production, since the level of collective co-production in which people engage is not strongly predicted by their background and can be influenced by public policy variables. ‘Nudges’ may help to encourage more collective co-production but they may need to be quite strong to succeed.
Logics of Violence in Criminal War
Authors: Lessing Benjamin
Published: June 2015

What kind of war is Mexico’s drug war? The prominent “criminal insurgency” approach helpfully focuses attention on cartel–state conflict, but unnecessarily redefines insurgency as “state-weakening,” eliding critical differences in rebels’ and cartels’ aims. Whereas rebels fight states, and cartels fight with one another, to conquer mutually prized territory and resources, cartels fight states “merely” to constrain their behavior and influence policy outcomes. This distinction yields a typology with theoretical consequences: decisive victory plays an important role in most models of civil war but is impossible or undesirable in wars of constraint. Theories of criminal war must therefore explain how ongoing coercive violence can be preferable to pacific strategies. I distinguish two such coercive logics of cartel–state conflict: violent lobbying and violent corruption. Lobbyings' more universalistic benefits elicit free riding, so turf war among cartels should make it rarer than violent corruption. This prediction accords with qualitative and quantitative evidence from Mexico, Colombia, and Brazil.
Goodness-of-fit of Multilevel Latent Class Models for Categorical Data
Authors: Nagelkerke Erwin , Oberski Daniel L. , Vermunt Jeroen K.
Published: June 2015

In the context of multilevel latent class models, the goodness-of-fit depends on multiple aspects, among which are two local independence assumptions. However, because of the lack of local fit statistics, the model and any issues relating to model fit can only be inspected jointly through global fit statistics. This hinders the search for model improvements, as it cannot be determined where misfit originates and which of the many model adjustments may improve its fit. Also, when relying solely on global fit statistics, assumption violations may become obscured, leading to wrong substantive results. In this paper, two local fit statistics are proposed to improve the understanding of the model, allow individual testing of the local independence assumptions, and inspect the fit of the higher level of the model. Through an application in which the local fit statistics group-variable residual and paired-case residual are used as guidance, it is shown that they pinpoint misfit, enhance the search for model improvements, provide substantive insight, and lead to a model with different substantive conclusions, which would likely not have been found when relying on global information criteria. Both residuals can be obtained in the user-friendly Latent GOLD 5.0 software package.