779 research outputs found
Phase transitions in a gas of anyons
Full text linkWe continue our numerical Monte Carlo simulation of a gas of closed loops on
a 3 dimensional lattice, however now in the presence of a topological term
added to the action corresponding to the total linking number between the
loops. We compute the linking number using certain notions from knot theory.
Adding the topological term converts the particles into anyons. Using the
correspondence that the model is an effective theory that describes the
2+1-dimensional Abelian Higgs model in the asymptotic strong coupling regime,
the topological linking number simply corresponds to the addition to the action
of the Chern-Simons term. We find the following new results. The system
continues to exhibit a phase transition as a function of the anyon mass as it
becomes small \cite{mnp}, although the phases do not change the manifestation
of the symmetry. The Chern-Simons term has no effect on the Wilson loop, but it
does affect the {\rm '}t Hooft loop. For a given configuration it adds the
linking number of the 't Hooft loop with all of the dynamical vortex loops to
the action. We find that both the Wilson loop and the 't Hooft loop exhibit a
perimeter law even though there are no massless particles in the theory, which
is unexpected.Comment: 6 pages, 5 figure
The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma
Get PDFBACKGROUND: The anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control. METHODS: Control and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days. RESULTS: When used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-α, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil. CONCLUSIONS: These results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor
Trust, regulatory processes and NICE decision-making: Appraising cost-effectiveness models through appraising people and systems.
Get PDFThis article presents an ethnographic study of regulatory decision-making regarding the cost-effectiveness of expensive medicines at the National Institute for Health and Care Excellence (NICE) in England. We explored trust as one important mechanism by which problems of complexity and uncertainty were resolved. Existing studies note the salience of trust for regulatory decisions, by which the appraisal of people becomes a proxy for appraising technologies themselves. Although such (dis)trust in manufacturers was one important influence, we describe a more intricate web of (dis)trust relations also involving various expert advisors, fellow committee members and committee Chairs. Within these complex chains of relations, we found examples of both more blind-acquiescent and more critical-investigative forms of trust as well as, at times, pronounced distrust. Difficulties in overcoming uncertainty through other means obliged trust in some contexts, although not in others. (Dis)trust was constructed through inferences involving abstract systems alongside actors’ oral and written presentations-of-self. Systemic features and ‘forced options’ to trust indicate potential insidious processes of regulatory capture
The impact of trauma-center care on mortality and function following pelvic ring and acetabular injuries
Get PDFABSTRACT
Background: Lower mortality and improved physical function following major polytrauma have been associated with treatment at level-1 trauma centers (TC) compared with that at non-trauma centers (NTC). This study investigates the impact of TC care on outcomes after pelvic and acetabular injuries.
Methods: Mortality and quality of life-related measures were compared among patients treated in 18 hospitals with level-1 trauma centers and 51 hospitals without trauma centers in 14 U.S. states. Complete data were obtained on 829 adult trauma patients (18-84 years old) with at least one pelvic ring or acetabular injury (OTA 61 or 62). We used inverse probability of treatment weighting to adjust for observable confounding.
Results: After adjustment for case mix, in-hospital mortality was significantly lower at TC versus NTC (RR 0.10, 95% CI 0.02-0.47), as was death by 90 days (RR 0.10, 95% CI 0.02-0.47), and one year (RR 0.21, 95% CI 0.06-0.76) for patients with more severe acetabular injuries (OTA 62-B or 62-C). Patients with combined pelvic ring and acetabular injuries treated at TC had lower mortality by 90 days (RR 0.34, 95% CI 0.14-0.82) and one year (RR 0.30 95% CI 0.14-0.68). Care at TC was also associated with mortality risk reduction for those with unstable pelvic ring injuries (OTA 61-B or 61-C) at one year (RR 0.21, 95%CI 0.06-0.76). Seventy-eight percent of included subjects discharged alive was available for interview at twelve months. Average absolute differences in SF-36 physical functioning and Musculoskeletal Functional Assessment at one year were 11.4 (95%CI 5.3 – 17.4) and 13.2 (1.7 – 24.7) respectively, indicating statistically and clinically significant improved outcomes with TC treatment for more severe acetabular injuries.
Conclusions: Mortality is reduced for patients with unstable pelvic and severe acetabular injuries when care is provided in a TC compared to NTC. Moreover, those with severe acetabular fractures experience improved physical function at one year. Patients with these injuries represent a well-defined subset of trauma patients that should be preferentially triaged or transferred to a Level-1 trauma center
Investigating the Effect of an Oxytetracycline Treatment on the Gut Microbiome and Antimicrobial Resistance Gene Dynamics in Nile Tilapia (Oreochromis niloticus)
Get PDFAntibiotics play a vital role in aquaculture where they are commonly used to treat bacterial diseases. However, the impact of antibiotic treatment on the gut microbiome and the development of antimicrobial resistance in Nile tilapia (Oreochromis niloticus) over time remains to be fully understood. In this study, fish were fed a single treatment of oxytetracycline (100 mg/kg/day) for eight days, followed by a 14-day withdrawal period. Changes in the distal gut microbiome were measured using 16S rRNA sequencing. In addition, the abundance of antimicrobial resistance genes was quantified using real-time qPCR methods. Overall, the gut microbiome community diversity and structure of Nile tilapia was resilient to oxytetracycline treatment. However, antibiotic treatment was associated with an enrichment in Plesiomonas, accompanied by a decline in other bacteria taxa. Oxytetracycline treatment increased the proportion of tetA in the distal gut of fish and tank biofilms of the treated group. Furthermore, the abundance of tetA along with other tetracycline resistance genes was strongly correlated with a number of microbiome members, including Plesiomonas. The findings from this study demonstrate that antibiotic treatment can exert selective pressures on the gut microbiome of fish in favour of resistant populations, which may have long-term impacts on fish health
TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms
Get PDFThe mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCβ3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCβ3 and the TRPV1 channel; 2) serotonin, or a selective agonist, α-methyl-serotonin (α-Me-5-HT), requires the presence of PLCβ3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCβ3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD^+ neurons that represent ≈90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1+ nociceptors led to a significant behavioral deficit for pruritogens, including α-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways
Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease
Get PDFMaple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress
Screening for coping style increases the power of gene expression studies
Get PDFBackground: Individuals of many vertebrate species show different stress coping styles and these have a striking influence on how gene expression shifts in response to a variety of challenges. Principal Findings: This is clearly illustrated by a study in which common carp displaying behavioural predictors of different coping styles (characterised by a proactive, adrenaline-based or a reactive, cortisol-based response) were subjected to inflammatory challenge and specific gene transcripts measured in individual brains. Proactive and reactive fish differed in baseline gene expression and also showed diametrically opposite responses to the challenge for 80% of the genes investigated. Significance: Incorporating coping style as an explanatory variable can account for some the unexplained variation that is common in gene expression studies, can uncover important effects that would otherwise have passed unnoticed and greatly enhances the interpretive value of gene expression data
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