Abstract An international expert panel was convened to deliberate the management of azole-resistant aspergillosis. In culture-positive cases, in vitro susceptibility testing should always be ...performed if antifungal therapy is intended. Different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. In confirmed invasive pulmonary aspergillosis due to an azole-resistant Aspergillus , the experts recommended a switch from voriconazole to liposomal amphotericin B (L-AmB; Ambisome® ). In regions with environmental resistance rates of ≥10%, a voriconazole–echinocandin combination or L-AmB were favoured as initial therapy. All experts recommended L-AmB as core therapy for central nervous system aspergillosis suspected to be due to an azole-resistant Aspergillus , and considered the addition of a second agent with the majority favouring flucytosine. Intravenous therapy with either micafungin or L-AmB given as either intermittent or continuous therapy was recommended for chronic pulmonary aspergillosis due to a pan-azole-resistant Aspergillus . Local and national surveillance with identification of clinical and environmental resistance patterns, rapid diagnostics, better quality clinical outcome data, and a greater understanding of the factors driving or minimising environmental resistance are areas where research is urgently needed, as well as the development of new oral agents outside the azole drug class.
An understanding of athlete ground reaction forces and moments (GRF/Ms) facilitates the biomechanist’s downstream calculation of net joint forces and moments, and associated injury risk. ...Historically, force platforms used to collect kinetic data are housed within laboratory settings and are not suitable for field-based installation. Given that Newton’s Second Law clearly describes the relationship between a body’s mass, acceleration, and resultant force, is it possible that marker-based motion capture can represent these parameters sufficiently enough to estimate GRF/Ms, and thereby minimize our reliance on surface embedded force platforms? Specifically, can we successfully use partial least squares (PLS) regression to learn the relationship between motion capture and GRF/Ms data? In total, we analyzed 11 PLS methods and achieved average correlation coefficients of 0.9804 for GRFs and 0.9143 for GRMs. Our results demonstrate the feasibility of predicting accurate GRF/Ms from raw motion capture trajectories in real-time, overcoming what has been a significant barrier to non-invasive collection of such data. In applied biomechanics research, this outcome has the potential to revolutionize athlete performance enhancement and injury prevention.
Graphical Abstract
Using data science to model high-fidelity motion and force plate data frees biomechanists from the laboratory
Background. The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)—related posttransplant lymphoproliferative disorder (PTLD) ...after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting. Methods. A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease. Results. One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extra-lymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0–1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival. Conclusions. More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.
Abstract Approximately 320,000 anterior cruciate ligament (ACL) injuries in the United States each year are non-contact injuries, with many occurring during a single-leg jump landing. To reduce ACL ...injury risk, one option is to improve muscle strength and/or the activation of muscles crossing the knee under elevated external loading. This study׳s purpose was to characterize the relative force production of the muscles supporting the knee during the weight-acceptance (WA) phase of single-leg jump landing and investigate the gastrocnemii forces compared to the hamstrings forces. Amateur male Western Australian Rules Football players completed a single-leg jump landing protocol and six participants were randomly chosen for further modeling and simulation. A three-dimensional, 14-segment, 37 degree-of-freedom, 92 muscle-tendon actuated model was created for each participant in OpenSim. Computed muscle control was used to generate 12 muscle-driven simulations, 2 trials per participant, of the WA phase of single-leg jump landing. A one-way ANOVA and Tukey post-hoc analysis showed both the quadriceps and gastrocnemii muscle force estimates were significantly greater than the hamstrings ( p <0.001). Elevated gastrocnemii forces corresponded with increased joint compression and lower ACL forces. The elevated quadriceps and gastrocnemii forces during landing may represent a generalized muscle strategy to increase knee joint stiffness, protecting the knee and ACL from external knee loading and injury risk. These results contribute to our understanding of how muscle׳s function during single-leg jump landing and should serve as the foundation for novel muscle-targeted training intervention programs aimed to reduce ACL injuries in sport.
Clin Microbiol Infect 2012; 18 (Suppl. 7): 9–18
As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to ...initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made.
DNA vaccines: progress and challenges Donnelly, John J; Wahren, Britta; Liu, Margaret A
The Journal of immunology (1950),
07/2005, Letnik:
175, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In the years following the publication of the initial in vivo demonstration of the ability of plasmid DNA to generate protective immune responses, DNA vaccines have entered into a variety of human ...clinical trials for vaccines against various infectious diseases and for therapies against cancer, and are in development for therapies against autoimmune diseases and allergy. They also have become a widely used laboratory tool for a variety of applications ranging from proteomics to understanding Ag presentation and cross-priming. Despite their rapid and widespread development and the commonplace usage of the term "DNA vaccines," however, the disappointing potency of the DNA vaccines in humans underscores the challenges encountered in the efforts to translate efficacy in preclinical models into clinical realities. This review will provide a brief background of DNA vaccines including the insights gained about the varied immunological mechanisms that play a role in their ability to generate immune responses.
Aspergillus PCR testing of serum provides technical simplicity but with potentially reduced sensitivity compared to whole-blood testing. With diseases for which screening to exclude disease ...represents an optimal strategy, sensitivity is paramount. The associated analytical study confirmed that DNA concentrations were greater in plasma than those in serum. The aim of the current investigation was to confirm analytical findings by comparing the performance of Aspergillus PCR testing of plasma and serum in the clinical setting. Standardized Aspergillus PCR was performed on plasma and serum samples concurrently obtained from hematology patients in a multicenter retrospective anonymous case-control study, with cases diagnosed according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (19 proven/probable cases and 42 controls). Clinical performance and clinical utility (time to positivity) were calculated for both kinds of samples. The sensitivity and specificity for Aspergillus PCR when testing serum were 68.4% and 76.2%, respectively, and for plasma, they were 94.7% and 83.3%, respectively. Eighty-five percent of serum and plasma PCR results were concordant. On average, plasma PCR was positive 16.8 days before diagnosis and was the earliest indicator of infection in 13 cases, combined with other biomarkers in five cases. On average, serum PCR was positive 10.8 days before diagnosis and was the earliest indicator of infection in six cases, combined with other biomarkers in three cases. These results confirm the analytical finding that the sensitivity of Aspergillus PCR using plasma is superior to that using serum. PCR positivity occurs earlier when testing plasma and provides sufficient sensitivity for the screening of invasive aspergillosis while maintaining methodological simplicity.
Stroke is an age-related disease. Recovery after stroke is associated with axonal sprouting in cortex adjacent to the infarct. The molecular program that induces a mature cortical neuron to sprout a ...new connection after stroke is not known. We selectively isolated neurons that sprout a new connection in cortex after stroke and compared their whole-genome expression profile to that of adjacent, non-sprouting neurons. This 'sprouting transcriptome' identified a neuronal growth program that consists of growth factor, cell adhesion, axonal guidance and cytoskeletal modifying molecules that differed by age and time point. Gain and loss of function in three distinct functional classes showed new roles for these proteins in epigenetic regulation of axonal sprouting, growth factor-dependent survival of neurons and, in the aged mouse, paradoxical upregulation of myelin and ephrin receptors in sprouting neurons. This neuronal growth program may provide new therapeutic targets and suggest mechanisms for age-related differences in functional recovery.
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