Serum Concentrations of Mannan-Binding Lectin (MBL) and MBL-Associated Serine Protease-2 and the Risk of Adverse Events in Pediatric Patients With Cancer and Fever in Neutropenia

Background. It is unknown whether serum concentrations of mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) influence the risk of adverse events (AEs) in children with cancer presenting with fever in neutropenia (FN). Methods. Pediatric patients with cancer presenting with FN after non-myeloablative chemotherapy were observed in a prospective multicenter study. Mannan-binding lectin and MASP-2 were measured using commercially available enzyme-linked immunosorbent assay in serum taken at cancer diagnosis. Multiple FN episodes per patient were allowed. Associations of MBL and MASP-2 with AE in general, with bacteremia, and with serious medical complications (SMC) during FN were analyzed using mixed logistic regression. Results. Of 278 FN episodes, AE was reported in 84 (30%), bacteremia was reported in 42 (15%), and SMC was reported in 16 (5.8%). Median MBL was 2152 ng/mL (range, 7–10 060). It was very low (<100) in 11 (9%) patients, low (100–999) in 36 (29%) patients, and normal (�1000) in 79 (63%) patients. Median MASP-2 was 410 ng/mL (range, 68–2771). It was low (<200) in 18 (14%) patients and normal in the remaining 108 (86%) patients. Mannan-binding lectin and MASP-2 were not significantly associated with AE or bacteremia. Normal versus low MBL was independently associated with a significantly higher risk of SMC (multivariate odds ratio, 12.8; 95% confidence interval, 1.01–163; P = .050). Conclusions. Mannan-binding lectin and MASP-2 serum concentrations were not found to predict the risk to develop AEs or bacteremia during FN. Normal MBL was associated with an increased risk of SMC during FN. This finding, in line with earlier studies, does not support the concept of MBL supplementation in MBL-deficient children with cancer presenting with FN.

Light-cone Wilson loop in classical lattice gauge theory

The transverse broadening of an energetic jet passing through a non-Abelian plasma is believed to be described by the thermal expectation value of a light-cone Wilson loop. In this exploratory study, we measure the light-cone Wilson loop with classical lattice gauge theory simulations. We observe, as suggested by previous studies, that there are strong interactions already at short transverse distances, which may lead to more efficient jet quenching than in leading-order perturbation theory. We also verify that the asymptotics of the Wilson loop do not change qualitatively when crossing the light cone, which supports arguments in the literature that infrared contributions to jet quenching can be studied with dimensionally reduced simulations in the space-like domain. Finally we speculate on possibilities for full four-dimensional lattice studies of the same observable, perhaps by employing shifted boundary conditions in order to simulate ensembles boosted by an imaginary velocity.

Epidemiology of Brucellosis and Q Fever in Linked Human and Animal Populations in Northern Togo

BACKGROUND: Although brucellosis (Brucella spp.) and Q Fever (Coxiella burnetii) are zoonoses of global importance, very little high quality data are available from West Africa. METHODS/PRINCIPAL FINDINGS: A serosurvey was conducted in Togo's main livestock-raising zone in 2011 in 25 randomly selected villages, including 683 people, 596 cattle, 465 sheep and 221 goats. Additionally, 464 transhumant cattle from Burkina Faso were sampled in 2012. The serological analyses performed were the Rose Bengal Test and ELISA for brucellosis and ELISA and the immunofluorescence assay (IFA) for Q Fever Brucellosis did not appear to pose a major human health problem in the study zone, with only 7 seropositive participants. B. abortus was isolated from 3 bovine hygroma samples, and is likely to be the predominant circulating strain. This may explain the observed seropositivity amongst village cattle (9.2%, 95%CI:4.3-18.6%) and transhumant cattle (7.3%, 95%CI:3.5-14.7%), with an absence of seropositive small ruminants. Exposure of livestock and people to C. burnetii was common, potentially influenced by cultural factors. People of Fulani ethnicity had greater livestock contact and a significantly higher seroprevalence than other ethnic groups (Fulani: 45.5%, 95%CI:37.7-53.6%; non-Fulani: 27.1%, 95%CI:20.6-34.7%). Appropriate diagnostic test cut-off values in endemic settings requires further investigation. Both brucellosis and Q Fever appeared to impact on livestock production. Seropositive cows were more likely to have aborted a foetus during the previous year than seronegative cows, when adjusted for age. This odds was 3.8 times higher (95%CI: 1.2-12.1) for brucellosis and 6.7 times higher (95%CI: 1.3-34.8) for Q Fever. CONCLUSIONS: This is the first epidemiological study of zoonoses in Togo in linked human and animal populations, providing much needed data for West Africa. Exposure to Brucella and C. burnetii is common but further research is needed into the clinical and economic impact.

Fever without a localizing source in infants

Fieber ohne Fokus beim Kleinkind

Canonical proof nets for classical logic

Proof nets provide abstract counterparts to sequent proofs modulo rule permutations; the idea being that if two proofs have the same underlying proof-net, they are in essence the same proof. Providing a convincing proof-net counterpart to proofs in the classical sequent calculus is thus an important step in understanding classical sequent calculus proofs. By convincing, we mean that (a) there should be a canonical function from sequent proofs to proof nets, (b) it should be possible to check the correctness of a net in polynomial time, (c) every correct net should be obtainable from a sequent calculus proof, and (d) there should be a cut-elimination procedure which preserves correctness. Previous attempts to give proof-net-like objects for propositional classical logic have failed at least one of the above conditions. In Richard McKinley (2010) [22], the author presented a calculus of proof nets (expansion nets) satisfying (a) and (b); the paper defined a sequent calculus corresponding to expansion nets but gave no explicit demonstration of (c). That sequent calculus, called LK∗ in this paper, is a novel one-sided sequent calculus with both additively and multiplicatively formulated disjunction rules. In this paper (a self-contained extended version of Richard McKinley (2010) [22]), we give a full proof of (c) for expansion nets with respect to LK∗, and in addition give a cut-elimination procedure internal to expansion nets – this makes expansion nets the first notion of proof-net for classical logic satisfying all four criteria.

A Prospective Multicenter SPOG 2003 FN Study of Microbiologically Defined Infections in Pediatric Cancer Patients with Fever and Neutropenia.

BACKGROUND Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. METHODS Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multi-center study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. RESULTS MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared to without MDI, fever (median, 5 [IQR 3-8] vs. 2 [IQR1-3] days, p < 0.001) and hospitalization (10 [6-14] vs. 5 [3-8] days, p < 0.001) lasted longer, transfer to the intensive care unit was more likely (13 of 95 [14%] vs. 7 of 346 [2.0%], p < 0.001), and antibiotics were given longer (10 [7-14] vs. 5 [4-7], p < 0.001). Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but the purposeful omission of coverage for coagulase negative staphylococci and enterococci was also taken into account (81% [95%CI 68 - 90] vs. 96.6% [95%CI 87 - 99.4], p = 0.004) CONCLUSIONS: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

Regional differences in symptomatic fever management among paediatricians in Switzerland: the results of a cross-sectional Web-based survey

AIMS In symptomatic fever management, there is often a gap between everyday clinical practice and current evidence. We were interested to see whether the three linguistic regions of Switzerland differ in the management of fever. METHODS A close-ended questionnaire, sent to 900 Swiss paediatricians, was answered by 322 paediatricians. Two hundred and fourteen respondents were active in the German speaking, 78 in the French speaking and 30 in the Italian speaking region. RESULTS Paediatricians from the French and Italian speaking regions identify a lower temperature threshold for initiating a treatment and more frequently reduce it for children with a history of febrile seizures. A reduced general appearance leads more frequently to a lower threshold for treatment in the German speaking than in the French and Italian speaking areas. Among 1.5 and 5-year-old children the preference for the rectal route is more pronounced in the German than in the French speaking region. French speaking respondents more frequently prescribe ibuprofen and an alternating regimen with two drugs than German speaking respondents. Finally, the stated occurrence of exaggerated fear of fever was higher in the German and Italian speaking regions. CONCLUSIONS Switzerland offers the opportunity to compare three different regions with respect to management of febrile children. This inquiry shows regional differences in symptomatic fever management and in the perceived frequency of exaggerated fear of fever. The gap between available evidence and clinical practice is more pronounced in the French and in the Italian speaking regions than in the German speaking region.

[Meningitis (I)--differential diagnosis; aseptic and chronic meningitis].

Meningitis is the most common serious manifestation of infection of the central nervous system. Inflammatory involvement of the subarachnoid space with meningeal irritation leads to the classical triad of headache, fever, and meningism, and to a pleocytosis of the cerebrospinal fluid (CSF). Meningitis is clinically categorized into an acute and chronic disease based on the acuity of symptoms. Acute meningitis develops over hours to days, while in chronic meningitis symptoms evolve over days or even weeks. Aseptic meningitis, in which no bacterial pathogen can be isolated by routine cultures, can mimic bacterial meningitis, but the disease has a much more favorable prognosis. Many cases of aseptic meningitis are caused by viruses, primarily enteroviruses, but bacteria and noninfectious etiologies also cause meningitis with negative cultures. Symptoms of meningeal inflammation with CSF pleocytosis that persist for more than 4 weeks define the chronic meningitis syndrome. The diagnosis is based on the patient history, clinical evidence of meningitis, CSF examination, and often imaging studies. The differential diagnosis is broad, and the predominant CSF cell type can provide clues as to the underlying disease. Empiric therapy is primarily based on the age of the patient, with modifications if there are positive findings on CSF gram stain or if the patient presents with special risk factors. In patients with chronic meningitis, a definite diagnosis is often not available or delayed for days, in which case empiric therapy may have to be initiated. It is important to cover the treatable causes of meningitis, for which the outcome is poor if treatment is delayed.

From emotion perception to emotion experience: Emotions evoked by pictures and classical music.

Most previous neurophysiological studies evoked emotions by presenting visual stimuli. Models of the emotion circuits in the brain have for the most part ignored emotions arising from musical stimuli. To our knowledge, this is the first emotion brain study which examined the influence of visual and musical stimuli on brain processing. Highly arousing pictures of the International Affective Picture System and classical musical excerpts were chosen to evoke the three basic emotions of happiness, sadness and fear. The emotional stimuli modalities were presented for 70 s either alone or combined (congruent) in a counterbalanced and random order. Electroencephalogram (EEG) Alpha-Power-Density, which is inversely related to neural electrical activity, in 30 scalp electrodes from 24 right-handed healthy female subjects, was recorded. In addition, heart rate (HR), skin conductance responses (SCR), respiration, temperature and psychometrical ratings were collected. Results showed that the experienced quality of the presented emotions was most accurate in the combined conditions, intermediate in the picture conditions and lowest in the sound conditions. Furthermore, both the psychometrical ratings and the physiological involvement measurements (SCR, HR, Respiration) were significantly increased in the combined and sound conditions compared to the picture conditions. Finally, repeated measures ANOVA revealed the largest Alpha-Power-Density for the sound conditions, intermediate for the picture conditions, and lowest for the combined conditions, indicating the strongest activation in the combined conditions in a distributed emotion and arousal network comprising frontal, temporal, parietal and occipital neural structures. Summing up, these findings demonstrate that music can markedly enhance the emotional experience evoked by affective pictures.

Modulation of corticospinal activity by strong emotions evoked by pictures and classical music: a transcranial magnetic stimulation study.

Using transcranial magnetic stimulation and skin conductance responses, we sought to clarify if, and to what extent, emotional experiences of different valences and intensity activate the hand-motor system and the associated corticospinal tract. For that purpose, we applied a newly developed method to evoke strong emotional experiences by the simultaneous presentation of musical and pictorial stimuli of congruent emotional valence. We uncovered enhanced motor-evoked potentials, irrespective of valence, during the simultaneous presentation of emotional music and picture stimuli (Combined conditions) compared with the single presentation of the two modalities (Picture/Music conditions). In contrast, vegetative arousal was enhanced during both the Combined and Music conditions, compared with the Picture conditions, again irrespective of emotional valence. These findings strongly indicate that arousal is a necessary, but not sufficient, prerequisite for triggering the motor system of the brain. We offer a potential explanation for this discrepant, but intriguing, finding in the paper.

Prognostic factors for advanced-stage human immunodeficiency virus-associated classical Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine plus combined antiretroviral therapy: A multi-institutional retrospective study.

BACKGROUND The treatment and outcomes of patients with human immunodeficiency virus (HIV)-associated Hodgkin lymphoma (HL) continue to evolve. The International Prognostic Score (IPS) is used to predict the survival of patients with advanced-stage HL, but it has not been validated in patients with HIV infection. METHODS This was a multi-institutional, retrospective study of 229 patients with HIV-associated, advanced-stage, classical HL who received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus combination antiretroviral therapy. Their clinical characteristics were presented descriptively, and multivariate analyses were performed to identify the factors that were predictive of response and prognostic of progression-free survival (PFS) and overall survival (OS). RESULTS The overall and complete response rates to ABVD in patients with HIV-associated HL were 91% and 83%, respectively. After a median follow-up of 5 years, the 5-year PFS and OS rates were 69% and 78%, respectively. In multivariate analyses, there was a trend toward an IPS score >3 as an adverse factor for PFS (hazard ratio [HR], 1.49; P=.15) and OS (HR, 1.84; P=.06). A cluster of differentiation 4 (CD4)-positive (T-helper) cell count <200 cells/μL was associated independently with both PFS (HR, 2.60; P=.002) and OS (HR, 2.04; P=.04). The CD4-positive cell count was associated with an increased incidence of death from other causes (HR, 2.64; P=.04) but not with death from HL-related causes (HR, 1.55; P=.32). CONCLUSIONS The current results indicate excellent response and survival rates in patients with HIV-associated, advanced-stage, classical HL who receive ABVD and combination antiretroviral therapy as well as the prognostic value of the CD4-positive cell count at the time of lymphoma diagnosis for PFS and OS. Cancer 2014. © 2014 American Cancer Society.

Quantum and classical criticality in a dimerized quantum antiferromagnet

A quantum critical point (QCP) is a singularity in the phase diagram arising because of quantum mechanical fluctuations. The exotic properties of some of the most enigmatic physical systems, including unconventional metals and superconductors, quantum magnets and ultracold atomic condensates, have been related to the importance of critical quantum and thermal fluctuations near such a point. However, direct and continuous control of these fluctuations has been difficult to realize, and complete thermodynamic and spectroscopic information is required to disentangle the effects of quantum and classical physics around a QCP. Here we achieve this control in a high-pressure, high-resolution neutron scattering experiment on the quantum dimer material TlCuCl3. By measuring the magnetic excitation spectrum across the entire quantum critical phase diagram, we illustrate the similarities between quantum and thermal melting of magnetic order. We prove the critical nature of the unconventional longitudinal (Higgs) mode of the ordered phase by damping it thermally. We demonstrate the development of two types of criticality, quantum and classical, and use their static and dynamic scaling properties to conclude that quantum and thermal fluctuations can behave largely independently near a QCP.

Proof internalization in generalized Frege systems for classical logic

We present a general method for inserting proofs in Frege systems for classical logic that produces systems that can internalize their own proofs.