1,197 research outputs found
Sometimes You Cannot Have It All: Party Switching and Affiliation Motivations as Substitutes
Existing research on when legislators switch parties reports inconsistent results about motivations for switching (e.g., office, ideology, and votes). I treat the motivations for party switching as substitutes and argue that many of the inconsistencies that persist can be explained by modelling the interactive effects between these motivations. For example, scholars differ in terms of whether they find that electoral considerations are an important determinant of party switching. The conflicting findings on the independent effects of electoral considerations are explained here by demonstrating that these effects are conditional on the level of office benefits a legislators enjoys, as well as the ideological distance between the legislator and party. More generally, the empirical analysis provides strong support for the substitution effect hypothesis. Thus, modelling interactive effects increases our understanding of party switching
International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs
This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose
Estimation of colorectal adenoma recurrence with dependent censoring
<p>Abstract</p> <p>Background</p> <p>Due to early colonoscopy for some participants, interval-censored observations can be introduced into the data of a colorectal polyp prevention trial. The censoring could be dependent of risk of recurrence if the reasons of having early colonoscopy are associated with recurrence. This can complicate estimation of the recurrence rate.</p> <p>Methods</p> <p>We propose to use midpoint imputation to convert interval-censored data problems to right censored data problems. To adjust for potential dependent censoring, we use information from auxiliary variables to define risk groups to perform the weighted Kaplan-Meier estimation to the midpoint imputed data. The risk groups are defined using two risk scores derived from two working proportional hazards models with the auxiliary variables as the covariates. One is for the recurrence time and the other is for the censoring time. The method described here is explored by simulation and illustrated with an example from a colorectal polyp prevention trial.</p> <p>Results</p> <p>We first show that midpoint imputation under an assumption of independent censoring will produce an unbiased estimate of recurrence rate at the end of the trial, which is often the main interest of a colorectal polyp prevention trial, and then show in simulations that the weighted Kaplan-Meier method using the information from auxiliary variables based on the midpoint imputed data can improve efficiency in a situation with independent censoring and reduce bias in a situation with dependent censoring compared to the conventional methods, while estimating the recurrence rate at the end of the trial.</p> <p>Conclusion</p> <p>The research in this paper uses midpoint imputation to handle interval-censored observations and then uses the information from auxiliary variables to adjust for dependent censoring by incorporating them into the weighted Kaplan-Meier estimation. This approach can handle a situation with multiple auxiliary variables by deriving two risk scores from two working PH models. Although the idea of this approach might appear simple, the results do show that the weighted Kaplan-Meier approach can gain efficiency and reduce bias due to dependent censoring.</p
MicroRNAs in pulmonary arterial remodeling
Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH
International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe
In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible
Titanium based cranial reconstruction using incremental sheet forming
In this paper, we report recent work in cranial plate manufacturing using incremental sheet forming (ISF) process. With a typical cranial shape, the ISF process was used to manufacture the titanium cranial shape by using different ISF tooling solutions with and without backing plates. Detailed evaluation of the ISF process including material deformation and thinning, geometric accuracy and surface finish was conducted by using a combination of experimental testing and Finite Element (FE) simulation. The results show that satisfactory cranial shape can be achieved with sufficient accuracy and surface finish by using a feature based tool path generation method and new ISF tooling design. The results also demonstrate that the ISF based cranial reconstruction has the potential to achieve considerable lead time reduction as compared to conventional methods for cranial plate manufacturing. This outcome indicates that there is a potential for the ISF process to achieve technological advances and economic benefits as well as improvement to quality of life
The implications of the United Nations Paris Agreement on climate change for globally significant biodiversity areas
Climate change is already affecting species and their distributions. Distributional range changes have occurred and are projected to intensify for many widespread plants and animals, creating associated risks to many ecosystems. Here, we estimate the climate change-related risks to the species in globally significant biodiversity conservation areas over a range of climate scenarios, assessing their value as climate refugia. In particular, we quantify the aggregated benefit of countries’ emission reduction pledges (Intended Nationally Determined Contributions and Nationally Determined Contributions under the Paris Agreement), and also of further constraining global warming to 2 °C above pre-industrial levels, against an unmitigated scenario of 4.5 °C warming. We also quantify the contribution that can be made by using smart spatial conservation planning to facilitate some levels of autonomous (i.e. natural) adaptation to climate change by dispersal. We find that without mitigation, on average 33% of each conservation area can act as climate refugium (or 18% if species are unable to disperse), whereas if warming is constrained to 2 °C, the average area of climate refuges doubles to 67% of each conservation area (or, without dispersal, more than doubles to 56% of each area). If the country pledges are fulfilled, an intermediate estimate of 47–52% (or 31–38%, without dispersal) is obtained. We conclude that the Nationally Determined Contributions alone have important but limited benefits for biodiversity conservation, with larger benefits accruing if warming is constrained to 2 °C. Greater benefits would result if warming was constrained to well below 2 °C as set out in the Paris Agreement
Getting inside acupuncture trials - Exploring intervention theory and rationale
<p>Abstract</p> <p>Background</p> <p>Acupuncture can be described as a complex intervention. In reports of clinical trials the mechanism of acupuncture (that is, the process by which change is effected) is often left unstated or not known. This is problematic in assisting understanding of how acupuncture might work and in drawing together evidence on the potential benefits of acupuncture. Our aim was to aid the identification of the assumed mechanisms underlying the acupuncture interventions in clinical trials by developing an analytical framework to differentiate two contrasting approaches to acupuncture (traditional acupuncture and Western medical acupuncture).</p> <p>Methods</p> <p>Based on the principles of realist review, an analytical framework to differentiate these two contrasting approaches was developed. In order to see how useful the framework was in uncovering the theoretical rationale, it was applied to a set of trials of acupuncture for fatigue and vasomotor symptoms, identified from a wider literature review of acupuncture and early stage breast cancer.</p> <p>Results</p> <p>When examined for the degree to which a study demonstrated adherence to a theoretical model, two of the fourteen selected studies could be considered TA, five MA, with the remaining seven not fitting into any recognisable model. When examined by symptom, five of the nine vasomotor studies, all from one group of researchers, are arguably in the MA category, and two a TA model; in contrast, none of the five fatigue studies could be classed as either MA or TA and all studies had a weak rationale for the chosen treatment for fatigue.</p> <p>Conclusion</p> <p>Our application of the framework to the selected studies suggests that it is a useful tool to help uncover the therapeutic rationale of acupuncture interventions in clinical trials, for distinguishing between TA and MA approaches and for exploring issues of model validity. English language acupuncture trials frequently fail to report enough detail relating to the intervention. We advocate using this framework to aid reporting, along with further testing and refinement of the framework.</p
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