219 research outputs found
Different yet complementary: two approaches to supporting victims of sexual violence in the UK
This article explores the strengths and limitations of two different types of settings that provide specialist support to victims of sexual violence in the UK: Sexual Assault Referral Centres (SARCs) and voluntary sector organizations such as Rape Crisis. Qualitative data from six case study sites and quantitative data from 35 sexual violence projects in England and Wales revealed that the type of setting affected the types of referrals received and this, in turn, shaped the services required by victims and thus the nature of the work preformed. Consequently, each type of project had different emphases in their workload with which they were particularly well equipped to handle. Each type also had its own unique challenges; for example, while there were notable benefits from delivering support in partnership models, such as SARCs, their affiliation with statutory partners was perceived by some as a disadvantage, especially for those seeking support in relation to historical sexual abuse. On the other hand, those delivering support in voluntary sector projects had to work harder to establish and maintain relationships with other agencies, but their independence was seen to be greater and this was perceived as a strength for gaining access to victims and maintaining their confidence. Both approaches had notable benefits and, given the diverse array of sexual violence victims in any given area, providing these two different, yet complementary, approaches to supporting them is recommended
Regulatory T Cells Are Dispensable for Tolerance to RBC Antigens
Autoimmune hemolytic anemia (AIHA) occurs when pathogenic autoantibodies against red blood cell (RBC) antigens are generated. Whilst the basic disease pathology of AIHA is well studied, the underlying mechanism(s) behind the failure in tolerance to RBC autoantigens are poorly understood. Thus, to investigate the tolerance mechanisms required for the establishment and maintenance of tolerance to RBC antigens, we developed a novel murine model. With this model, we evaluated the role of regulatory T cells (Tregs) in tolerance to RBC-specific antigens. Herein, we show that neither sustained depletion of Tregs nor immunization with RBC-specific proteins in conjunction with Treg depletion led to RBC-specific autoantibody generation. Thus, these studies demonstrate that Tregs are not required to prevent autoantibodies to RBCs and suggest that other tolerance mechanisms are likely involved
The Role of the Immunological Synapse in Differential Effects of APC Subsets in Alloimmunization to Fresh, Non-stored RBCs
Background: Each year, over 5 million red blood cell (RBC) transfusions are administered to patients in the USA. Despite the therapeutic benefits of RBC transfusions, there are associated risks. RBC-specific alloantibodies may form in response to antigenic differences between RBC donors and recipients; these alloantibodies can be a problem as they may mediate hemolysis or pose barriers to future transfusion support. While there is currently no reliable way to predict which RBC recipients will make an alloantibody response, risk factors such as inflammation have been shown to correlate with increased rates of RBC alloimmunization. The underlying mechanisms behind how inflammation mediates alloantibody production are incompletely defined.Methods: To assess erythrophagocytosis, mice were treated with PBS or inflammatory stimuli followed by a transfusion of allogeneic RBCs labeled with a lipophilic dye. At multiple time points, RBC consumption and expression of activation makers by leukocytes was evaluated. To determine which antigen presenting cell (APC) subset(s) were capable of promoting allogeneic T cell activation, sorted leukocyte populations (which had participated in erythrophagocytosis) were co-cultured in vitro with allogeneic CD4+ T cells; T cell proliferation and ability to form immunological synapses with APCs were determined.Results: Upon transfusion of fresh allogeneic RBCs, multiple APCs consumed transfused RBCs. However, only CD8+ and CD11b+ dendritic cells formed productive immunological synapses with allogeneic T cells and stimulated proliferation. Importantly, allogeneic T cell activation and RBC alloantibody production occurred in response to RBC transfusion alone, and transfusion in the context of inflammation enhanced RBC consumption, the number of immune synapses, allogeneic T cell proliferation, and the rate and magnitude of alloantibody production.Conclusions: These data demonstrate that regardless of the ability to participate in RBC consumption, only a subset of APCs are capable of forming an immune synapse with T cells thereby initiating an alloantibody response. Additionally, these data provide mechanistic insight into RBC alloantibody generation
Detection of toxins and harmful algal bloom cells in shellfish hatcheries and efforts toward removal
As the start of the supply chain for the aquaculture industry, hatcheries are a crucial component in the success of oyster and northern quahog (hard clam) aquaculture on the East Coast of the US. Intermittent failures in hatchery production slow industry growth and reduce profits. To begin investigations into the possible role of algal toxins in hatchery production failure, post-treatment hatchery water from one research and four commercial hatcheries in lower Chesapeake Bay, USA, was sampled for (1) toxin presence and (2) harmful algal bloom (HAB) cell enumeration. Overall, seven toxin classes, likely produced by six different HAB species, were detected in post- treatment hatchery water, despite a lack of visually identifiable HAB cells within the facility. Toxins detected include pectenotoxin-2, goniodomin A, karlotoxin-1 and karlotoxin-3, okadaic acid and dinophysistoxin-1, azaspiracid-1 and azaspiracid-2, brevetoxin-2, and microcystin-LR. In a second, more targeted study, two batches of source water were followed and sampled at each step of a water-treatment process in the VIMS Aquaculture Genetics and Breeding Technology Center research hatchery in Gloucester Point, Virginia, USA. Two treatment steps showed particular promise for decreasing the concentrations of the three toxins detected in the source water, 24-h circulation through sand filters and activated charcoal filtration. Toxin concentrations of pectenotoxin-2, 3.53 ± 0.56 pg m
Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia.
In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance
Improved Single-Shot Qubit Readout Using Twin RF-SET Charge Correlations
High fidelity qubit readout is critical in order to obtain the thresholds
needed to implement quantum error correction protocols and achieve
fault-tolerant quantum computing. Large-scale silicon qubit devices will have
densely-packed arrays of quantum dots with multiple charge sensors that are, on
average, farther away from the quantum dots, entailing a reduction in readout
fidelities. Here, we present a readout technique that enhances the readout
fidelity in a linear SiMOS 4-dot array by amplifying correlations between a
pair of single-electron transistors, known as a twin SET. By recording and
subsequently correlating the twin SET traces as we modulate the dot detuning
across a charge transition, we demonstrate a reduction in the charge readout
infidelity by over one order of magnitude compared to traditional readout
methods. We also study the spin-to-charge conversion errors introduced by the
modulation technique, and conclude that faster modulation frequencies avoid
relaxation-induced errors without introducing significant spin flip errors,
favouring the use of the technique at short integration times. This method not
only allows for faster and higher fidelity qubit measurements, but it also
enhances the signal corresponding to charge transitions that take place farther
away from the sensors, enabling a way to circumvent the reduction in readout
fidelities in large arrays of qubits
Retrospective and prospective assessments of gambling-related behaviors across the female menstrual cycle
Background and aims: Despite increases in female gambling, little research investigates female-specific factors affecting gambling behavior (GB). Although research suggests that some addictive behaviors may fluctuate across menstrual cycle phase (MCP), gambling requires further investigation. In two studies, we examined associations between MCP and three risky GBs: time spent gambling, money spent gambling, and the probability of consuming alcohol while gambling. Associations between MCP and negative affect were also examined in Study 2. We predicted that, consistent with self-medication theory, increases in negative affect (Study 2) and risky GBs (Studies 1 and 2) would occur premenstrually/menstrually relative to other phases. Methods: Data were obtained from 33 female gamblers using a retrospective timeline followback procedure (Study 1) and from 20 female gamblers using a prospective 32-day, daily diary method (Study 2). In Study 2, salivary progesterone levels verified self-reported MCP validity. Results: Findings revealed significant, but somewhat inconsistent, MCP effects on GBs across studies. The self-medication hypothesis was partially supported. Increases relative to another MCP(s) were found for alcohol consumption while gambling premenstrually, time spent gambling menstrually/premenstrually, money spent gambling menstrually, and negative affect premenstrually. Unexpectedly, findings more consistently indicated that GBs increased during ovulation, suggestive of enhanced reward sensitivity. Progesterone assays validated self-reported MCP (Study 2). Discussion and conclusions: The results suggest a role of ovarian hormones on negative affect and GBs in females. This research could lead to the identification of female-specific factors affecting gambling and the development of more effective interventions for females with, or at risk for, problematic gambling
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The relationship between parent and child dysfunctional beliefs about sleep and child sleep
Cognitive theories emphasise the role of dysfunctional beliefs about sleep in the development and maintenance of sleep-related problems (SRPs). The present research examines how parents' dysfunctional beliefs about children's sleep and child dysfunctional beliefs about sleep are related to each other and to children's subjective and objective sleep. Participants were 45 children aged 11 -12 years and their parents. Self-report measures of dysfunctional beliefs about sleep and child sleep were completed by children, mothers and fathers. Objective measures of child sleep were taken using actigraphy. The results showed that child dysfunctional beliefs about sleep were correlated with father (r=.43, p<.05) and mother (r=.43, p<.05) reported child SRPs, and with Sleep Onset Latency (r=.34, p<.05). Maternal dysfunctional beliefs about child sleep were related to child SRPs as reported by mothers (r=.44, p<.05), and to child dysfunctional beliefs about sleep (r=.37, p<.05). Some initial evidence was found for a mediation pathway in which child dyfunctional beliefs mediate the relationship between parent dysfunctional beliefs and child sleep. The results support the cognitive model of SRPs and contribute to the literature by providing the first evidence of familial aggregation of dysfunctional beliefs about sleep
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