Correlations, fluctuations and stability of a finite-size network of coupled oscillators

The incoherent state of the Kuramoto model of coupled oscillators exhibits marginal modes in mean field theory. We demonstrate that corrections due to finite size effects render these modes stable in the subcritical case, i.e. when the population is not synchronous. This demonstration is facilitated by the construction of a non-equilibrium statistical field theoretic formulation of a generic model of coupled oscillators. This theory is consistent with previous results. In the all-to-all case, the fluctuations in this theory are due completely to finite size corrections, which can be calculated in an expansion in 1/N, where N is the number of oscillators. The N -> infinity limit of this theory is what is traditionally called mean field theory for the Kuramoto model.Comment: 25 pages (2 column), 12 figures, modifications for resubmissio

Induction and effector phase of allergic lung inflammation is independent of CCL21/CCL19 and LT-beta

The chemokines CCL21 and CCL19, and cell bound TNF family ligand lymphotoxin beta (LTβ), have been associated with numerous chronic inflammatory diseases. A general role in chronic inflammatory diseases cannot be assumed however; in the case of allergic inflammatory disease, CCL21/CCL19 and LTβ have not been associated with the induction, recruitment, or effector function of Th2 cells nor dendritic cells to the lung. We have examined the induction of allergic inflammatory lung disease in mice deficient in CCL21/CCL19 or LTβ and found that both kinds of mice can develop allergic lung inflammation. To control for effects of priming differences in knockout mice, adoptive transfers of Th2 cells were also performed, and they showed that such effector cells had equivalent effects on airway hyper-responsiveness in both knockout background recipients. Moreover, class II positive antigen presenting cells (B cells and CD11c+ dendritic cells) showed normal recruitment to the peribronchial spaces along with CD4 T cells. Thus, the induction of allergic responses and recruitment of both effector Th2 cells and antigen presenting cells to lung peribronchial spaces can develop independently of CCL21/CCL19 and LTβ

Electroweak bubbles and sphalerons

We consider non-perturbative solutions of the Weinberg-Salam model at finite temperature. We employ an effective temperature-dependent potential yielding a first order phase transition. In the region of the phase transition, there exist two kinds of static, spherically symmetric solutions: sphalerons and bubbles. We analyze these solutions as functions of temperature. We consider the most general spherically symmetric fluctuations about the two solutions and construct the discrete modes in the region of the phase transition. Sphalerons and bubbles both possess a single unstable mode. We present simple approximation formulae for these levels.Comment: 14 pages, plain tex, 9 figures appended as postscript files at the end of the paper. THU-93/0

Fluctuation corrections to bubble nucleation

The fluctuation determinant which determines the preexponential factor of the transition rate for minimal bubbles is computed for the electroweak theory with $\sin \Theta_W = 0$. As the basic action we use the three-dimensional high-temperature action including, besides temperature dependent masses, the $T \Phi^3$ one-loop contribution which makes the phase transition first order. The results show that this contribution (which has then to be subtracted from the exact result) gives the dominant contribution to the one-loop effective action. The remaining correction is of the order of, but in general larger than the critical bubble action and suppresses the transition rate. The results for the Higgs field fluctuations are compared with those of an approximate heat kernel computation of Kripfganz et al., good agreement is found for small bubbles, strong deviations for large thin-wall bubbles.Comment: 19 pages, LaTeX, no macros, no figure

Combined Cisplatinum and Laser Thermal Therapy for Palliation of Recurrent Head and Neck Tumors

In recent years endoscopically controlled laser-induced thermal therapy (LITT) has been increasingly accepted as a minimally invasive method for palliation of advanced or recurrent head and neck or gastrointestinal cancer. Previous studies have shown that adjuvant chemotherapy can potentiate endoscopic laser thermal ablation of obstructing tumors leading to improved palliation in advanced cancer patients. Eight patients with recurrent head and neck tumors volunteered to enroll as part of an ongoing phase II LITT clinical trial, and also elected to be treated with systemic chemotherapy (cisplatin, 80 mg/m2) followed 24 h later by palliative laser thermal ablation. Laser treatments were repeated in patients with residual disease or recurrence for a total of 27 LITT sessions. Four of the 8 patients treated with laser thermal chemotherapy remained alive after a median follow-up of 12 months. Of the 12 tumor sites treated, complete responses were located in the oral cavity (3), oropharynx (1), hypopharynx (1), maxillary sinus (1), and median survival for these patients was 9.5 months. This initial experience with cisplatinum-based laser chemotherapy indicates both safety and therapeutic potential for palliation of advanced head and neck cancer but this must be confirmed by longer follow-up in a larger cohort of patients

Hydrodynamic Stability Analysis of Burning Bubbles in Electroweak Theory and in QCD

Assuming that the electroweak and QCD phase transitions are first order, upon supercooling, bubbles of the new phase appear. These bubbles grow to macroscopic sizes compared to the natural scales associated with the Compton wavelengths of particle excitations. They propagate by burning the old phase into the new phase at the surface of the bubble. We study the hydrodynamic stability of the burning and find that for the velocities of interest for cosmology in the electroweak phase transition, the shape of the bubble wall is stable under hydrodynamic perturbations. Bubbles formed in the cosmological QCD phase transition are found to be a borderline case between stability and instability.Comment: preprint # SLAC-PUB-5943, SCIPP 92/56 38 pages, 10 figures (submitted via `uufiles'), phyzzx format minor snafus repaire

Turning Around the Sphaleron Bound: Electroweak Baryogenesis in an Alternative Post-inflationary Cosmology

The usual sphaleron bound and the statement of the impossibility of baryon production at a second order phase transition or analytic cross-over are reformulated in the first part of the paper as requirements of the expansion rate of the Universe at the electroweak scale. With an (exact or effective) additional contribution to the energy density scaling as 1/a^6, which dominates until just before nucleosynthesis, the observed baryon asymmetry may be produced at the electroweak scale in simple extensions of the Minimal Standard Model, even in the case that the phase transition is not first order. We focus our attention on one such cosmology, in which the Universe goes through a period termed `kination' in which its energy is dominated by the kinetic energy of a scalar field. The required kinetic energy dominated modes can occur either as a field rolls down an exponential (or steeper) potential, or in the oscillation of a field about the minimum of a steep power-law potential. We implement in detail the former case with a single exponential field first driving inflation, and then rolling into a kinetic energy dominated mode. Reheating is achieved using an alternative to the usual mechanism due to Spokoiny, in which the Universe is `reheated' by particle creation in the expanding background. Density perturbations of the magnitude required for structure formation may also be generated. We show that the analogous model for the power-law potential cannot be consistently implemented. In models with inflation driven by a second field and the usual mechanism of reheating (by decay of the inflaton) the required kinetic energy dominated cosmology is viable in both types of potential.Comment: 44 pages, ReVTeX, with 9 postscipt figures (included); minor modifications to figure

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

Background: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.<p></p> Methods: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.<p></p> Results: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.<p></p> Conclusions: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.<p></p&gt

Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial

Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. The primary endpoint was least square mean change in MADRS for each active treatment compared with placebo at 13 weeks, starting with the 180 mg dose, using a fixed sequence step-down closed test procedure. Between May 2019 and August 2021, 329 individuals were screened for eligibility, 231 entered the open-label enrichment phase (days 1–8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was −6.1 (95% confidence interval 1.0 to 11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. The most common adverse events were headache, dizziness and anxiety. During the randomized phase of the study, most patient dosing occurred at home. R-107 tablets were effective, safe and well tolerated in a patient population with TRD, enriched for initial response to R-107 tablets. ClinicalTrials.gov registration: ACTRN12618001042235