Airway Inflammation and Bronchial Hyperresponsiveness in Elite Cross-Country Skiers and in Patients with Newly Diagnosed Asthma: A Bronchial Biopsy Study

The objective of these studies was to evaluate possible airway inflammation and remodeling at the bronchial level in cross-country skiers without a prior diagnosis of asthma, and relate the findings to patients with mild chronic asthma and patients with newly diagnosed asthma. We also studied the association of airway inflammatory changes and bronchial hyperresponsivess (BHR), and treatment effects in cross-country skiers and in patients with newly diagnosed asthma. Bronchial biopsies were obtained from the subjects by flexible bronchoscopy, and the inflammatory cells (eosinophils, mast cells, T-lymphocytes, macrophages, and neutrophils) were identified by immunohistochemistry. Tenascin (Tn) immunoreactivity in the bronchial basement membrane (BM) was identified by immunofluorescence staining. Lung function was measured with spirometry, and BHR was assessed by methacholine (skiers) or histamine (asthmatics) challenges. Skiers with BHR and asthma-like symptoms were recruited to a drug-intervention study. Skiers were given treatment (22 weeks) with placebo or budesonide (400 µg bid). Patients with newly diagnosed asthma were given treatment for 16 weeks with placebo, salmeterol (SLM) (50 µg bid), fluticasone propionate (FP) (250 µg bid), or disodium cromoglicate (DSCG) (5 mg qid). Bronchial biopsies were obtained at baseline and at the end of the treatment period. In the skiers a distinct airway inflammation was evident. In their bronchial biopsy specimens, T-lymphocyte, macrophage, and eosinophil counts were, respectively greater by 43-fold (P<0.001), 26-fold (P<0.001, and 2-fold (P<0.001) in skiers, and by 70-fold (p>0.001), 63-fold (P<0.001), and 8-fold (P<0.001) in asthmatic subjects than in controls. In skiers, neutrophil counts were more than 2-fold greater than in asthmatic subjects (P<0.05). Tn expression was higher in skiers than in controls and lower in skiers than in mild asthmatics. No significant changes were seen between skiers with or without BHR in the inflammatory cell counts or Tn expression. Treatment with inhaled budesonide did not attenuate asthma-like symptoms, the inflammatory cell infiltration, or BM Tn expression in the skiers. In newly diagnosed asthmatic patients, SLM, FP, and DSCG reduced asthma symptoms, and need for rescue medication (P<0.04). BHR was reduced by doubling doses 2.78, 5.22, and 1.35 respectively (all P<0.05). SLM and placebo had no effect on cell counts or Tn expression. FP and DSCG reduced eosinophil counts in the bronchial biopsy specimens (P<0.02 and <0.048, respectively). No significant change in tenascin expression appeared in any treatment group. Regarding to atopy, no significant differences existed in the inflammatory cell counts in the bronchial mucosa of subjects with newly diagnosed asthma or in elite cross country skiers. Tn expression in the BM was significantly higher in atopic asthma than in those with nonatopic asthma. Airway inflammation occurred in elite cross-country skiers with and without respiratory symptoms or BHR. Their inflammatory cell pattern differed from that in asthma. Infiltration with eosinophils, macrophages, and mast cells was milder, but lymphocyte counts did not differ from counts in asthmatic airways. Neutrophilic infiltration was more extensive in skiers than in asthmatics. Remodeling took place in the skiers’ airways, as reflected by increased expression of BM tenascin These inflammatory changes and Tn expression may be caused by prolonged exposure of the lower airways to inadequately humidified cold air. In skiers inflammatory changes and remodeling were not reversed with anti-inflammatory treatment. In contrast, in patients with newly diagnosed asthma, anti-inflammatory treatment did attenuate eosinophilic inflammation in the bronchial mucosa. In skiers, anti-inflammatory treatment did not attenuate BHR as it did in asthmatic patients. The BHR in skiers was attenuated spontaneously during placebo treatment, with no difference from budesonide treatment. Lower training intensity during the treatment period may explain this spontaneous decrease in BHR. The origin of BHR probably differs in skiers and in asthmatics. No significant association between BHR and inflammatory cell counts or between BHR and Tn expression was evident in cross-country skiers or asthmatic subjects. Airway remodeling differed between atopic and nonatopic asthma. As opposed to nonatopic asthma, Tn expression was higher in atopic asthma and is related to inflammatory cell densities.

QCD and total cross-sections : photons and hadrons

In this contribution, we discuss a total cross-section model which can be applied to both photon and purely hadronic processes. We find that the model can reproduce photo-production cross-sections, as well as extrapolation of gamma*p processes to gamma p using Vector Meson Dominance models, with minimal modifications from the proton case.

QCD and total cross-sections : photons and hadrons

In this contribution, we discuss a total cross-section model which can be applied to both photon and purely hadronic processes. We find that the model can reproduce photo-production cross-sections, as well as extrapolation of gamma*p processes to gamma p using Vector Meson Dominance models, with minimal modifications from the proton case.

Vibrational phase relaxation of O–H stretch in bulk water: Role of large amplitude angular jumps and negative cross-correlations among the forces on the O–H bond

The ultrafast vibrational phase relaxation of O–H stretch in bulk water is investigated in molecular dynamics simulations. The dephasing time (T2) of the O–H stretch in bulk water calculated from the frequency fluctuation time correlation function (Cω(t)) is in the range of 70–80 femtosecond (fs), which is comparable to the characteristic timescale obtained from the vibrational echo peak shift measurements using infrared photon echo [W.P. de Boeij, M.S. Pshenichnikov, D.A. Wiersma, Ann. Rev. Phys. Chem. 49 (1998) 99]. The ultrafast decay of Cω(t) is found to be responsible for the ultrashort T2 in bulk water. Careful analysis reveals the following two interesting reasons for the ultrafast decay of Cω(t). (A) The large amplitude angular jumps of water molecules (within 30–40 fs time duration) provide a large scale contribution to the mean square vibrational frequency fluctuation and gives rise to the rapid spectral diffusion on 100 fs time scale. (B) The projected force, due to all the atoms of the solvent molecules on the oxygen (FO(t)) and hydrogen (FH(t)) atom of the O–H bond exhibit a large negative cross-correlation (NCC). We further find that this NCC is partly responsible for a weak, non-Arrhenius temperature dependence of the dephasing rate.

Total cross-section at LHC from minijets and soft gluon resummation in the infrared region

A model for total cross-sections incorporating QCD jet cross-sections and soft gluon resummation is described and compared with present data on pp and pp cross-sections. Predictions for LHC are presented for different parameter sets. It is shown that they differ according to the small x-behaviour of available parton density functions.

Infrared gluons, intrinsic transverse momentum and rising total cross-sections

We discuss the infrared limit for soft gluon k(t)-resummation and relate it to physical observables such as the intrinsic transverse momentum and the high energy limit of total cross-sections.

Novel application of a discrete choice experiment to identify preferences for a national healthcare-associated infection surveillance programme: A cross-sectional study

Objective: To identify key stakeholder preferences and priorities when considering a national healthcare-associated infection (HAI) surveillance programme through the use of a discrete choice experiment (DCE). Setting: Australia does not have a national HAI surveillance programme. An online web-based DCE was developed and made available to participants in Australia. Participants: A sample of 184 purposively selected healthcare workers based on their senior leadership role in infection prevention in Australia. Primary and secondary outcomes: A DCE requiring respondents to select 1 HAI surveillance programme over another based on 5 different characteristics (or attributes) in repeated hypothetical scenarios. Data were analysed using a mixed logit model to evaluate preferences and identify the relative importance of each attribute. Results: A total of 122 participants completed the survey (response rate 66%) over a 5-week period. Excluding 22 who mismatched a duplicate choice scenario, analysis was conducted on 100 responses. The key findings included: 72% of stakeholders exhibited a preference for a surveillance programme with continuous mandatory core components (mean coefficient 0.640 (p<0.01)), 65% for a standard surveillance protocol where patient-level data are collected on infected and non-infected patients (mean coefficient 0.641 (p<0.01)), and 92% for hospital-level data that are publicly reported on a website and not associated with financial penalties (mean coefficient 1.663 (p<0.01)). Conclusions: The use of the DCE has provided a unique insight to key stakeholder priorities when considering a national HAI surveillance programme. The application of a DCE offers a meaningful method to explore and quantify preferences in this setting.

Asymmetric cross-coupled differential pair configuration to realize neuron activation function and its derivative

In this brief, we present a new circuit technique to generate the sigmoid neuron activation function (NAF) and its derivative (DNAF). The circuit makes use of transistor asymmetry in cross-coupled differential pair to obtain the derivative. The asymmetry is introduced through external control signal, as and when required. This results in the efficient utilization of the hard-ware by realizing NAF and DNAF using the same building blocks. The operation of the circuit is presented in the subthreshold region for ultra low-power applications. The proposed circuit has been experimentally prototyped and characterized as a proof of concept on the 1.5-mum AMI technology.

Unfolding of Plasmodium falciparum Triosephosphate Isomerase in Urea and Guanidinium Chloride: Evidence for a Novel Disulfide Exchange Reaction in a Covalently Cross-Linked Mutant†

The conformational stability of Plasmodium falciparum triosephosphate isomerase (TIMWT) enzyme has been investigated in urea and guanidinium chloride (GdmCl) solutions using circular dichroism, fluorescence, and size-exclusion chromatography. The dimeric enzyme is remarkably stable in urea solutions. It retains considerable secondary, tertiary, and quaternary structure even in 8 M urea. In contrast, the unfolding transition is complete by 2.4 M GdmCl. Although the secondary as well as the tertiary interactions melt before the perturbation of the quaternary structure, these studies imply that the dissociation of the dimer into monomers ultimately leads to the collapse of the structure, suggesting that the interfacial interactions play a major role in determining multimeric protein stability. The C-m(urea)/C-m(GdmCl) ratio (where C-m is the concentration of the denaturant required at the transition midpoint) is unusually high for triosephosphate isomerase as compared to other monomeric and dimeric proteins. A disulfide crosslinked mutant protein (Y74C) engineered to form two disulfide cross-links across the interface (13-74') and (13'-74) is dramatically destablized in urea. The unfolding transition is complete by 6 M urea and involves a novel mechanism of dimer dissociation through intramolecular thiol-disulfide exchange.

Measurement of Particle Production and Inclusive Differential Cross Sections in pbar{p} Collisions at sqrt{s}=1.96 TeV

We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

Measurement of particle production and inclusive differential cross sections in pp̅ collisions at √s=1.96 TeV

We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

Diffraction and Total Cross-Section at the Tevatron and the LHC

At the Tevatron, the total p_bar-p cross-section has been measured by CDF at 546 GeV and 1.8 TeV, and by E710/E811 at 1.8 TeV. The two results at 1.8 TeV disagree by 2.6 standard deviations, introducing big uncertainties into extrapolations to higher energies. At the LHC, the TOTEM collaboration is preparing to resolve the ambiguity by measuring the total p-p cross-section with a precision of about 1 %. Like at the Tevatron experiments, the luminosity-independent method based on the Optical Theorem will be used. The Tevatron experiments have also performed a vast range of studies about soft and hard diffractive events, partly with antiproton tagging by Roman Pots, partly with rapidity gap tagging. At the LHC, the combined CMS/TOTEM experiments will carry out their diffractive programme with an unprecedented rapidity coverage and Roman Pot spectrometers on both sides of the interaction point. The physics menu comprises detailed studies of soft diffractive differential cross-sections, diffractive structure functions, rapidity gap survival and exclusive central production by Double Pomeron Exchange.