Red cell ABO incompatibility and production of tumour necrosis factor-alpha

Tumour necrosis factor-alpha (TNF) is a major mediator of diverse pathophysiological events similar to those of haemolytic transfusion reactions (HTR), such as fever, intravascular coagulation and organ failure. However, the possible role of TNF in HTR has not been investigated. We have constructed an in vitro whole blood model of HTR to examine whether TNF may be produced in red cell ABO incompatibility. TNF was observed in plasma, in a dose dependent manner, when ABO incompatible red cells were added, but not with compatible (group O) cells. Plasma TNF levels were maximal at 2 h, and declined to control levels by 24 h. Haemolysis of incompatible red cells was accompanied by TNF production. Immune haemolysis induced TNF gene expression by buffy coat leucocytes, as determined by Northern blot analysis. Heat inactivation of plasma abolished TNF production, whereas prior treatment with interferongamma augmented the response. These results demonstrate that a major cytokine is produced in response to red cell incompatibility, and suggest that TNF may play a role in the pathogenesis of haemolytic transfusion reactions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75627/1/j.1365-2141.1991.tb04485.x.pd

Radio Observations of the January 20, 2005 X-Class Event

We present a multi-frequency and multi-instrument study of the 20 January 2005 event. We focus mainly on the complex radio signatures and their association with the active phenomena taking place: flares, CMEs, particle acceleration and magnetic restructuring. As a variety of energetic particle accelerators and sources of radio bursts are present, in the flare-ejecta combination, we investigate their relative importance in the progress of this event. The dynamic spectra of {Artemis-IV-Wind/Waves-Hiras with 2000 MHz-20 kHz frequency coverage, were used to track the evolution of the event from the low corona to the interplanetary space; these were supplemented with SXR, HXR and gamma-ray recordings. The observations were compared with the expected radio signatures and energetic-particle populations envisaged by the {Standard Flare--CME model and the reconnection outflow termination shock model. A proper combination of these mechanisms seems to provide an adequate model for the interpretation of the observational data.Comment: Accepted for publication in Solar Physic

Disease and treatment-related burden in patients with acromegaly who are biochemically controlled on injectable somatostatin receptor ligands

Medical treatment for acromegaly commonly involves receiving intramuscular or deep subcutaneous injections of somatostatin receptor ligands (SRLs) in most patients. In addition to side effects of treatment, acromegaly patients often still experience disease symptoms even when therapy is successful in controlling GH and IGF-1 levels. Symptoms and side effects can negatively impact patients' health-related quality of life. In this study, we examine the disease- and treatment-related burden associated with SRL injections as reported through the use of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ(C)) and clinician-reported symptom severity through the Acromegaly Index of Severity (AIS). Patients included in this analysis were enrolled in a randomized phase 3 study, were biochemically-controlled (an IGF-1 = 6 months with a stable dose of either long- acting octreotide or lanreotide monotherapy for >= 4 months. The sample (N = 91) was 65% female, 91% Caucasian, with a mean [standard deviation (SD)] age of 53 (1) years. Two-thirds of patients reported that they still experience acromegaly symptoms; 82% of these said they experience symptoms all of the time. Three-fourths experienced gastrointestinal (GI) side effects after injections, and 77% experienced treatment-related injection site reactions (ISRs). Patients commonly reported that these interfered with their daily life, leisure, and work activities. Those with higher symptom severity, as measured by the AIS, scored significantly worse on several Acro-TSQ domains: Symptom Interference, GI Interference, Treatment Satisfaction, and Emotional Reaction. Despite being biochemically controlled with injectable SRLs, most patients reported experiencing acromegaly symptoms that interfere with daily life, leisure, and work. GI side effects and ISRs were also common. This study highlights the significant disease burden that still persists for patients with acromegaly that have achieved biochemical control with the use of injectable SRLs.Diabetes mellitus: pathophysiological changes and therap

Cost-effectiveness of internet-based cognitive-behavioral treatment for bulimia nervosa: Results of a randomized controlled trial

Objective: To evaluate the cost-effectiveness of Internet-based cognitive-behavioral therapy for bulimia nervosa (CBT-BN) compared to face-to-face delivery of CBT-BN. Methods: This study is a planned secondary analysis of data from a randomized clinical trial. Participants were 179 adults (98% female, mean age = 28 years) meeting DSM-IV criteria for bulimia nervosa who were randomized to group face-to-face or group Internet-based CBTBN for 16 sessions during 20 weeks. The cost-effectiveness analysis was conducted from a third-party payor perspective, and a partial societal perspective analysis was conducted to investigate cost-utility (ie, cost per gain in quality-adjusted life-years) and patient outof-pocket travel-related costs. Net health care costs were calculated from protocol and nonprotocol health care services using third-party payor cost estimates. The primary outcome measure in the clinical trial was abstinence from binge eating and purging, and the trial start and end dates were 2008 and 2016. Results: The mean cost per abstinent patient at posttreatment was $7,757 (95$4,515, $13,361) for face-to-face and$11,870 (95% CL, $6,486,$22,188) for Internet-based CBT-BN, and at 1-year follow-up was $16,777 (95$10,298, $27,042) for face-to-face and$14,561 (95% CL, $10,165,$21,028) for Internet-based CBT-BN. There were no statistically significant differences between treatment arms in cost-effectiveness or costutility at posttreatment or 1-year follow-up. Out-of-pocket patient costs were significantly higher for face-to-face (mean [95% CL] = $178 [$127, $140]) than Internet-based ($50 [$50,$50]) therapy. Conclusions: Third-party payor cost-effectiveness of Internet-based CBT-BN is comparable with that of an accepted standard. Internet-based dissemination of CBT-BN may be a viable alternative for patients geographically distant from specialist eating disorder services who have an unmet need for treatment

Predictors of dropout in face-to-face and internet-based cognitive-behavioral therapy for bulimia nervosa in a randomized controlled trial

Objective: We sought to identify predictors and moderators of failure to engage (i.e., pretreatment attrition) and dropout in both Internet-based and traditional face-to-face cognitive-behavioral therapy (CBT) for bulimia nervosa. We also sought to determine if Internet-based treatment reduced failure to engage and dropout. Method: Participants (N = 191, 98% female) were randomized to Internet-based CBT (CBT4BN) or traditional face-to-face group CBT (CBTF2F). Sociodemographics, clinical history, eating disorder severity, comorbid psychopathology, health status and quality of life, personality and temperament, and treatment-related factors were investigated as predictors. Results: Failure to engage was associated with lower perceived treatment credibility and expectancy (odds ratio [OR] = 0.91, 95% CI: 0.82, 0.97) and body mass index (BMI) (OR = 1.10; 95% CI: 1.03, 1.18). Dropout was predicted by not having a college degree (hazard ratio [HR] = 0.55; 95% CI: 0.37, 0.81), novelty seeking (HR = 1.02; 95% CI: 1.01, 1.03), previous CBT experience (HR = 1.77; 95% CI: 1.16, 2.71), and randomization to the individual's nonpreferred treatment format (HR = 1.95, 95% CI: 1.28, 2.96). Discussion: Those most at risk of failure to engage had a higher BMI and perceived treatment as less credible and less likely to succeed. Dropout was associated with less education, higher novelty seeking, previous CBT experience, and a mismatch between preferred and assigned treatment. Contrary to expectations, Internet-based CBT did not reduce failure to engage or dropout

Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Search for heavy Majorana or Dirac neutrinos and right-handed W gauge bosons in final states with charged leptons and jets in pp collisions at √s = 13 TeV with the ATLAS detector

A search for heavy right-handed Majorana or Dirac neutrinos NR and heavy right-handed gauge bosons WR is performed in events with energetic electrons or muons, with the same or opposite electric charge, and energetic jets. The search is carried out separately for topologies of clearly separated final-state products (“resolved” channel) and topologies with boosted final states with hadronic and/or leptonic products partially overlapping and reconstructed as a large-radius jet (“boosted” channel). The events are selected from pp collision data at the LHC with an integrated luminosity of 139 fb−1 collected by the ATLAS detector at √s = 13 TeV. No significant deviations from the Standard Model predictions are observed. The results are interpreted within the theoretical framework of a left-right symmetric model, and lower limits are set on masses in the heavy righthanded WR boson and NR plane. The excluded region extends to about m(WR) = 6.4 TeV for both Majorana and Dirac NR neutrinos at m(NR) < 1 TeV. NR with masses of less than 3.5 (3.6) TeV are excluded in the electron (muon) channel at m(WR) = 4.8 TeV for the Majorana neutrinos, and limits of m(NR) up to 3.6 TeV for m(WR) = 5.2 (5.0) TeV in the electron (muon) channel are set for the Dirac neutrinos. These constitute the most stringent exclusion limits to date for the model considered