227 research outputs found
Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults
Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent
risk factor for developing dementia in later life. We here aimed to evaluate
associations between recurrent mTBIs, cognition, and gray matter volume and
microstructure as revealed by structural magnetic resonance imaging (MRI) in
the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-
middle-aged subjects, who reported two or more sports-related mTBIs, with the
last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex-
and education matched controls with no history of mTBI (control group). All
participants received comprehensive neuropsychological testing, and high
resolution T1-weighted and diffusion tensor MRI in order to assess cortical
thickness (CT) and microstructure, hippocampal volume, and ventricle size.
Compared to the control group, subjects of the mTBI group presented with lower
CT within the right temporal lobe and left insula using an a priori region of
interest approach. Higher number of mTBIs was associated with lower CT in
bilateral insula, right middle temporal gyrus and right entorhinal area. Our
results suggest persistent detrimental effects of recurrent mTBIs on CT
already in young-to-middle-aged adults. If additional structural deterioration
occurs during aging, subtle neuropsychological decline may progress to
clinically overt dementia earlier than in age-matched controls, a hypothesis
to be assessed in future prospective trials
Chromosomal localization of PemIK toxin-antitoxin system results in the loss of toxicity : characterization of from Staphylococcus pseudintermedius
Estimating Discrete Markov Models From Various Incomplete Data Schemes
The parameters of a discrete stationary Markov model are transition
probabilities between states. Traditionally, data consist in sequences of
observed states for a given number of individuals over the whole observation
period. In such a case, the estimation of transition probabilities is
straightforwardly made by counting one-step moves from a given state to
another. In many real-life problems, however, the inference is much more
difficult as state sequences are not fully observed, namely the state of each
individual is known only for some given values of the time variable. A review
of the problem is given, focusing on Monte Carlo Markov Chain (MCMC) algorithms
to perform Bayesian inference and evaluate posterior distributions of the
transition probabilities in this missing-data framework. Leaning on the
dependence between the rows of the transition matrix, an adaptive MCMC
mechanism accelerating the classical Metropolis-Hastings algorithm is then
proposed and empirically studied.Comment: 26 pages - preprint accepted in 20th February 2012 for publication in
Computational Statistics and Data Analysis (please cite the journal's paper
Remaking Europe: the new manufacturing as an engine for growth. Bruegel Blueprint Series 26 September 2017
Europe needs to know how it can realise the potential for industrial rejuvenation. How well are European firms responding to the new opportunities for growth, and in which global value chains are they developing these new activities? The policy discussion on the future of manufacturing requires an understanding of the changing role of manufacturing in Europeâs growth agenda
Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice
<div><p>Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.</p></div
Phase II evaluation of mitoxantrone in advanced pancreatic carcinoma: A Southwest Oncology Group study
Patient with advanced adenocarcinoma of the pancreas and no prior chemotherapy were treated on a Phase II trial of mitoxantrone. Doses were adjusted for hepatic dysfunction as defined by bilirubin. Twenty-four patients with a bilirubin ⩜ 1.5 mg% received mitoxantrone 12 mg/m 2 i.v. repeated every three weeks. Myelosuppression in the form of leukopenia was the major toxicity. There were no responses in twenty-four evaluable patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45319/1/10637_2004_Article_BF00216928.pd
Exploiting antitumor immunity to overcome relapse and improve remission duration
Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patientâs lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patientâs own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinibâs effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-Îł-producing-CD8+, -CD4+, -NK cell, and IFN-Îł-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types
Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial
Background: Ion channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recov ery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes.
Methods: RECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned.
Results: The trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52â1.14) with amiodarone and 0.97 (0.81â1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27â2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37â3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 Ă 103/mcL for nadir platelet count identified the phenogroup at greatest risk of dying.
Conclusions: In this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis
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