56 research outputs found
Preliminary Injunctive Relief in Patent Cases: Repairing Irreparable Harm
Unlike a permanent injunction, which is an equitable remedy awarded to an injured party, a preliminary injunction is a form of interlocutory relief that is imposed by a court to preserve the status quo during litigation. In patent cases decided since (and often before) the Supreme Court’s 2006 decision in eBay v. MercExchange, courts have applied a four-factor test when considering the issuance of a permanent injunction. A similar test has evolved for preliminary injunctions, following the Court’s decision in Winter v. NRDC. Both the eBay and Winter tests rely heavily on whether the patentee is likely to suffer “irreparable” harm if an injunction is not granted. Yet despite the very different statutory bases and underlying reasoning for preliminary versus permanent injunctions, almost no scholarly attention or judicial reasoning has been devoted to an analysis of the meaning of irreparable harm in the context of preliminary injunctions. In order to gain a better understanding of the information that courts consider when deciding motions for preliminary injunctions, we collected data from 211 published district court opinions in patent cases decided between 2013 and 2020 in which a preliminary injunction was sought. Based on our findings, as well as recent opinions of the Federal Circuit, we find that much uncertainty and lack of clarity surrounding preliminary injunctive relief can be reduced, or eliminated, by explicit recognition that irreparable harm has (or should have) a certain meaning, and that meaning is not the same as harm. We propose a new four-factor test for irreparable harm when assessing the issuance of preliminary injunctions in patent cases. That test provides that to be considered irreparable, harm should be that which, in the absence of an injunction, 1) would unduly disrupt the status quo, 2) is imminent and likely to occur, 3) is causally linked to the alleged infringement, and 4) unlikely to result in payment of adequate compensation. We believe that the application of this new test will make the preliminary injunction analysis more certain and economically sensible, and better fitted to achieve its stated statutory goals
US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report
This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in
Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference
Frontotemporal dementia and its subtypes: a genome-wide association study
SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center
Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia
Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
Funder: QingLan Research Project of Jiangsu for Outstanding Young TeachersFunder: Project funded by Postdoctoral Science Foundation of Xuzhou Medical UniversityFunder: Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical UniversityAbstract: We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA\xe2\x80\x99s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration
Tendencias de la cultura y cambio organizacional: estudio de caso
La imagen corporativa en relación con el medio se evidencia en el informe de Deloitte (2018) sobre tendencias del capital humano, en donde se reportan alrededor de 11.000 cuestionarios aplicados a gerentes de 140 países y 150 líderes de empresas colombianas, el planteamiento realizado sugiere que el capital social cobra tanto importancia como el físico y el financiero. Estos aspectos están relacionados con la identidad corporativa y cómo se relaciona a su vez con la cultura y la gestión del en la organización. La cultura y la gestión del cambio han cobrado mucho interés para las personas que guían las organizaciones, los estudios realizados por Deloitte en 2017 se focalizaron en la relación de la cultura y el compromiso como elementos importantes del empleado; los resultados del estudio dejan en evidencia cómo la habilidad de las organizaciones para afrontar inconvenientes de compromiso y cultura tenían una reducción del 14% con respecto al año anterior, estos datos permiten entender la complejidad del ambiente en el ámbito laboral y dan cuenta de la importancia de desarrollar conocimiento válido que oriente a académicos y empresarios para que puedan abordar
de una manera adecuada estos aspectos.1a edició
CXCR4 involvement in neurodegenerative diseases
Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a 'network' of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases
Preliminary Injunctive Relief in Patent Cases: Repairing Irreparable Harm
Unlike a permanent injunction, which is an equitable remedy awarded to an injured party, a preliminary injunction is a form of interlocutory relief that is imposed by a court to preserve the status quo during litigation. In patent cases decided since (and often before) the Supreme Court’s 2006 decision in eBay v. MercExchange, courts have applied a four-factor test when considering the issuance of a permanent injunction. A similar test has evolved for preliminary injunctions, following the Court’s decision in Winter v. NRDC. Both the eBay and Winter tests rely heavily on whether the patentee is likely to suffer “irreparable” harm if an injunction is not granted. Yet despite the very different statutory bases and underlying reasoning for preliminary versus permanent injunctions, almost no scholarly attention or judicial reasoning has been devoted to an analysis of the meaning of irreparable harm in the context of preliminary injunctions. In order to gain a better understanding of the information that courts consider when deciding motions for preliminary injunctions, we collected data from 211 published district court opinions in patent cases decided between 2013 and 2020 in which a preliminary injunction was sought. Based on our findings, as well as recent opinions of the Federal Circuit, we find that much uncertainty and lack of clarity surrounding preliminary injunctive relief can be reduced, or eliminated, by explicit recognition that irreparable harm has (or should have) a certain meaning, and that meaning is not the same as harm. We propose a new four-factor test for irreparable harm when assessing the issuance of preliminary injunctions in patent cases. That test provides that to be considered irreparable, harm should be that which, in the absence of an injunction, 1) would unduly disrupt the status quo, 2) is imminent and likely to occur, 3) is causally linked to the alleged infringement, and 4) unlikely to result in payment of adequate compensation. We believe that the application of this new test will make the preliminary injunction analysis more certain and economically sensible, and better fitted to achieve its stated statutory goals
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