69 research outputs found
Dimeric FcÎłR ectodomains detect pathogenic anti-platelet factor 4-heparin antibodies in heparin-induced thromobocytopenia
Background
Heparinâinduced thrombocytopenia (HIT) is a major and potentially fatal consequence of antibodies produced against platelet factor 4 (PF4)âheparin complexes following heparin exposure. Not all antiâPF4âheparin antibodies are pathogenic, so overdiagnosis can occur, with resulting inappropriate use of alternative anticoagulation therapies that have associated risks of bleeding. However, definitive platelet functional assays are not widely available for routine analysis.
Objectives
To assess the utility of dimeric recombinant soluble FcÎłRIIa (rsFcÎłRIIa) ectodomains for detecting HIT antibodies.
Patients/Methods
Plasma from 27 suspected HIT patients were tested for pathogenic antiâPF4âheparin antibodies by binding of a novel dimeric FcÎłRIIa ectodomain probe. Plasmas were also tested by the use of PF4âheparin IgG ELISA, the HemosIL AcuStar HIT IgGâspecific assay, and a serotonin release assay (SRA).
Results
The dimeric rsFcÎłRIIa test produced no false positives and excluded four samples that were positive by IgG ELISA. In this small patient cohort, the novel assay correctly assigned 93% of the suspected HIT patients, with two of the HIT patients being scored as false negatives. The improved discrimination of the novel assay over the IgG ELISA, which scored four false positives, supports the mechanistic interpretation that binding of dimeric rsFcÎłRIIa detects pairs of closely spaced IgG antibodies in PF4âheparin immune complexes.
Conclusions
This study found the cellâfree, functionâbased dimeric rsFcÎłRIIa assay to be convenient, simple, and potentially predictive of HIT. The assay had improved specificity over the IgG ELISA, and correlated strongly with the AcuStar HIT IgGâspecific assay, warranting further evaluation of its potential to identify HIT in larger patient cohorts
Challenging sex segregation: A philosophical evaluation of the football associationâs rules on mixed football
The Football Association (FA) has been under pressure to allow girls to play in mixed teams since 1978, following 12-year old Theresa Bennettâs application to play with boys in a local league. In 1991, over a decade after Bennettâs legal challenge, the FA agreed to remove its ban on mixed football and introduced Rule C4 in order to permit males and females to play together in competitive matches under the age of 11. More recently, following a campaign by parents, coaches, local Members of Parliament and the Womenâs Sport Foundation, the FA agreed to trial mixed football for the under-12 to under-15 age categories in order to establish, among other things, the risk of injury to players in sex-integrated competitions. A series of exponential changes ensued: between 2010 and 2014, the age at which mixed football was permitted increased from U11 to U16. In 2015, the FA announced the decision to raise the age limit on mixed football from U16 to U18 for the forthcoming 2015â2016 season. We critically examine the reasons given by the FA for enforcing segregated participation beyond the age of 18, namely that males have an unfair advantage and that females face an unacceptable risk of injury. We also discuss the argument that removing the ban might harm the womenâs game. In conclusion, we suggest that the FA ought to abandon the ban on mixed football over the age of 18
Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models
Both community ecology and conservation biology seek further understanding of
factors governing the advance of an invasive species. We model biological
invasion as an individual-based, stochastic process on a two-dimensional
landscape. An ecologically superior invader and a resident species compete for
space preemptively. Our general model includes the basic contact process and a
variant of the Eden model as special cases. We employ the concept of a
"roughened" front to quantify effects of discreteness and stochasticity on
invasion; we emphasize the probability distribution of the front-runner's
relative position. That is, we analyze the location of the most advanced
invader as the extreme deviation about the front's mean position. We find that
a class of models with different assumptions about neighborhood interactions
exhibit universal characteristics. That is, key features of the invasion
dynamics span a class of models, independently of locally detailed demographic
rules. Our results integrate theories of invasive spatial growth and generate
novel hypotheses linking habitat or landscape size (length of the invading
front) to invasion velocity, and to the relative position of the most advanced
invader.Comment: The original publication is available at
www.springerlink.com/content/8528v8563r7u2742
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses
In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum
The economic well-being of nations is associated with positive daily situational experiences
People in economically advantaged nations tend to evaluate their life as more positive overall and report greater well-being than people in less advantaged nations. But how does positivity manifest in the daily life experiences of individuals around the world? The present study asked 15,244 college students from 62 nations, in 42 languages, to describe a situation they experienced the previous day using the Riverside Situational Q-sort (RSQ). Using expert ratings, the overall positivity of each situation was calculated for both nations and individuals. The positivity of the average situation in each nation was strongly related to the economic development of the nation as measured by the Human Development Index (HDI). For individualsâ daily experiences, the economic status of their nation also predicted the positivity of their experience, even more than their family socioeconomic status. Further analyses revealed the specific characteristics of the average situations for higher HDI nations that make their experiences more positive. Higher HDI was associated with situational experiences involving humor, socializing with others, and the potential to express emotions and fantasies. Lower HDI was associated with an increase in the presence of threats, blame, and hostility, as well as situational experiences consisting of family, religion, and money. Despite the increase in a few negative situational characteristics in lower HDI countries, the overall average experience still ranged from neutral to slightly positive, rather than negative, suggesting that greater HDI may not necessarily increase positive experiences but rather decrease negative experiences. The results illustrate how national economic status influences the lives of individuals even within a single instance of daily life, with large and powerful consequences when accumulated across individuals within each nation
Effect of Duration of Feed Restriction on the Laying House Performance of Confinement Reared Pullets
Platelet ad hesion receptors and (patho)physiological thrombus formation
In thrombus formation associated with
hemostasis or thrombotic disease, blood platelets first
undergo a rapid transition from a circulating state to an
adherent state, followed by activation and aggregation.
Under flow conditions in the bloodstream, this process
potentially involves platelet-platelet, plateletendothelium,
platelet-subendothelial matrix, and
platelet-leukocyte interactions. Specific adhesion
receptors on platelets mediate these interactions, by
engaging counter-receptors on other cells, or noncellular
ligands in the plasma or matrix. The
glycoprotein (GP) Ib-IX-V complex on platelets initiates
adhesion at high shear stress by binding the adhesive
ligand, von Willebrand Factor (vWF). GP Ib-IX-V may
also mediate platelet-endothelium or platelet-leukocyte
adhesion, by recognition of P-selectin or Mac-1,
respectively. Other membrane glycoproteins, such as the
collagen receptor GP VI, may trigger platelet activation
at low shear rates. Engagement of GP Ib-IX-V or GP VI
leads ultimately to platelet aggregation mediated by the
integrin, aIIbB3 (GP IIb-IIIa). This review will focus on
recent advances in understanding structure-activity
relationships of GP Ib-IX-V, its role in initiating
thrombus formation, and its emerging relationships with
other vascular cell adhesion receptors
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