3,236 research outputs found
Serum cholesterol levels in neutropenic patients with fever
Hypocholesterolemia, which often accompanies infectious diseases has been suggested to serve as a prognostic marker in hospitalized patients. Even though patients with chemotherapyinduced leukopenia are at high risk of infection and mortality, only limited information is available on serum cholesterol levels in these patients. We therefore measured serum cholesterol levels in 17 patients with hematological malignancies during chemotherapyinduced neutropenia and correlated it with clinical outcome. Patients with fever (>38.5 degreesC) showed a significant decrease in serum cholesterol levels within 24 hours. Eight days after onset of the fever nonsurvivors had significantly lower serum cholesterol levels (median 2.09 mmol/l, range 0.492.79, n=6) compared to survivors (median 3.23 mmol/l, range 1.684.86, n=11). Cholesterol levels in survivors returned to baseline levels at the time of discharge from the hospital. At the onset of fever, serum levels of inflammatory cytokines interleukin-6, tumor necrosis factor (TNF) and soluble TNF receptors p55 and p75 were elevated in all patients, but only TNF and TNF receptor p75 levels were significantly different in survivors and nonsurvivors. Our data suggest that a decrease in serum cholesterol levels is a prognostic marker in neutropenic patients with fever. Release of inflammatory cytokines may in part be responsible for hypocholesterolemia in these patients
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Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals.
BackgroundA previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.MethodsIn order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).ResultsOf the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available.ConclusionOff-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies
Language universals rely on social cognition: Computational models of the use of this and that to redirect the receiver’s attention
Demonstratives—simple referential devices like this and that—are linguistic universals, but their meaning varies cross-linguistically. In languages like English and Italian, demonstratives are thought to encode the referent’s distance from the producer (e.g., that one means “the one far away from me”), while in others, like Portuguese and Spanish, they encode relative distance from both producer and receiver (e.g., aquel means “the one far away from both of us”). Here we propose that demonstratives are also sensitive to the receiver’s focus of attention, hence requiring a deeper form of social cognition than previously thought. We provide initial empirical and computational evidence for this idea, suggesting that producers use demonstratives to redirect the receiver’s attention towards the intended referent, rather than only to indicate its physical distance
I Know You Know I’m Signaling: Novel gestures are designed to guide observers’ inferences about communicative goals
On the generality of the Cohen and Glashow constraints on the neutrino velocity
We discuss the kinematic limits for the process \nu_\mu \rightarrow \nu_\mu +
e^+ + e^- in the assumption that neutrinos are superluminal. We derive our
results by assuming that: i) it exists one reference frame in which energy and
momentum are conserved; ii) the Hamilton-Jacobi equation v=dE/dp is valid; iii)
the present experimental information on the neutrino velocity at different
energies are correct. We show that the considered process cannot be avoided
unless very peculiar neutrino dispersion laws are assumed.Comment: 5 page
Current Concepts for Patellar Dislocation
Context: Patellar dislocation usually occurs to the lateral side, leading to ruptures of the Medial Patellofemoral Ligament (MPFL) in about 90% of the cases. Even though several prognostic factors are identified for patellofemoral instability after patellar dislocation so far, the appropriate therapy remains a controversial issue.
Evidence Acquisition: Authors searched the Medline library for studies on both surgical and conservative treatment for patellar dislocation and patellofemoral instability. Additionally, the reference list of each article was searched for additional studies.
Results: A thorough analysis of the anatomical risk factors with a particular focus on patella alta, increased Tibial Tuberosity-Trochlear Groove (TT-TG) distance, trochlear dysplasia as well as torsional abnormalities should be performed early after the first dislocation to allow adequate patient counseling. Summarizing the results of all published randomized clinical trials and comparing surgical and conservative treatment after the first-time patellar dislocation until today indicated no significant evident difference for children, adolescents, and adults. Therefore, nonoperative treatment was indicated after a first-time patellar dislocation in the vast majority of patients.
Conclusions: Surgical treatment for patellar dislocation is indicated primarily in case of relevant concomitant injuries such as osteochondral fractures, and secondarily for recurrent dislocations
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Determining constants in Shor`s discrete log algorithm over Zp
We compute the number of gates and laser pulses required in Shor`s algorithm for finding {ital r} in the equation {ital g{sup r} = x(mod p)} where {ital p} is a prime, and {ital g} and {ital x} are given elements of the multiplicative group {ital Z{sup *}{sub p}}. Because the discrete logarithm algorithm is similar to the factoring algorithm we may utilize gates designed for use in factoring
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Differentiating anxiety from fear: An experimental-pharmacological approach
Gray’s theory of personality postulates that fear and anxiety are distinct emotional systems with only the latter being sensitive to anxiolytic drugs. His work was mainly based on animal research and translational studies validating his theory are scarce. Previous work in humans showed an influence of the benzodiazepine lorazepam on both systems, however, dependent on dosage (1 and 2mg) and personality differences in negative emotionality. The present study aims to replicate these findings, and in addition tests the drug threshold effect by introducing a lower dosage of 0.5mg lorazepam.
Fifty healthy adults (23 males, agemean 22.40, SD±3.68) participated in an experimental threat-avoidance paradigm designed to dissociate risk assessment intensity (RAI, reflecting anxiety) and flight intensity (FI, reflecting fear) and completed two self-report questionnaires assessing facets of negative emotionality (Spielberger Trait Anxiety Inventory and Fear Survey Schedule). In a randomized placebo-controlled within-subject design, 0.5mg and 1mg of lorazepam were applied per os. Saccadic peak velocity was assessed by means of eye-tracking in order to control for sedating drug effects.
Results showed the expected and specific anxiolytic effect of lorazepam on RAI, however only in the 0.5mg condition. FI was not influenced by lorazepam and previous findings of interaction effects of lorazepam with self-reported negative emotionality could not be corroborated.
Overall, this study demonstrates anxiolytic effects of lorazepam in dosages ≤ 1mg in the absence of a drug effect on fear using a translational behavioural task. However, a putative moderating role of personality on defensive behaviour has to be clarified in future research
Positive schizotypy and Motor Impulsivity correlate with response aberrations in ventral attention network during inhibitory control
Inhibitory control (IC) aberrations are present in various psychopathologies, including schizophrenia spectrum and personality disorders, especially in association with antisocial or violent behaviour. We investigated behavioural and neural associations between IC and psychopathology-related traits of schizotypy [Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)], psychopathy [Triarchic Psychopathy Measure (TriPM)], and impulsivity [Barratt Impulsiveness Scale (BIS-11)], using a novel Go/No-Go Task (GNG) featuring human avatars in 78 healthy adults (25 males, 53 females; mean age = 25.96 years, SD = 9.85) and whole-brain functional magnetic resonance imaging (fMRI) in a separate sample of 22 right-handed healthy individuals (7 males, 15 females; mean age = 24.13 years, SD = 5.40). Behaviourally, O-LIFE Impulsive Nonconformity (impulsive, anti-social, and eccentric behaviour) significantly predicted 16 % of variance in false alarms (FAs). O-LIFE Unusual Experiences (positive schizotypy) and BIS-11 Motor Impulsivity predicted 15 % of d prime (d’) (sensitivity index) for the fastest (400 ms) GNG trials. When examined using fMRI, higher BIS-11 Motor Impulsivity uniquely, and also together with Unusual Experiences, was associated with lower activity in the left lingual gyrus during successful inhibition (correct No-Go over baseline). Additionally, higher Impulsive Nonconformity was associated with lower activity in the caudate nucleus and anterior cingulate during No-Go compared to Go stimuli reactions. Positive schizotypy, motor, and antisocial-schizotypal impulsivity correlate with some common but mostly distinct neural activation patterns during response inhibition in areas within or associated with the ventral attention network
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